IMMS Flashcards

Question

What is Gametogenesis in males?

Answer 1

* Primordial germ cell --> lots of mitoses --> spermatogonia (mature sperm) * Some mitosis occurs in embryonic stages to produce primary spermatocytes present at birth * Mitosis really begins during puberty and continues throughout life * Meiotic division commence at puberty * Cytoplasm divides evenly * After meiosis 2 --> 4 equal sized gametes * Millions of mature sperm continually produced * Process takes 60-65 days * 100/200 million sperm per ejaculate

Answer 2

* Primordial germ cell --> 30 mitoses --> oogonia * Oogonia enter prophase 1 of Meiosis 2 by 7th month of intrauterine life * Process suspended * Cells enter ovulation 10-50 yrs later * Cytoplasm divides unequally- 1 egg & 3 Polar bodies ( that apoptose) * Meiosis 1 is completed at ovulation ( then cells remain in suspended animation)- at this point there is 1 big cell, 1 small cell each with diploid DNA. then go on to divide again ( after fertilisation) to form 1 big cell (egg) and 3 small cells (polar bodies) * Meiosis 2 is only complete if fertilisation occurs

Answer 3

* Non- disjunction | * Gonadal mosaicism

Answer 4

* Failure of chromosome pairs to separate in Meiosis 1 or sister chromatids to separate properly in Meiosis 2 1. Down syndrome (Trisomy 21- RISK INCREASES WITH AGE FOR MALES AND FEMALES 75% maternal meiosis I, 25% maternal meiosis II, 3-5% paternal non disjunction 2. Turners syndrome (Monosomy {loss of a chromosome}- Only 1 X chromosome)

Answer 5

* Occurs when precursor germline cells to ova or spermatozoa are a mixture of two or more genetically different cell lines (due to errors in mitosis) * One cell line is normal, the other is mutated * Incidence increases with advancing paternal age * Parent is healthy ( since genetic change is only in germline so all other cells are unaffected- have usual genetic components), but the foetus may have genetic diseases * More common in males * Can be observed with any inheritance pattern, but most commonly autosomal dominant and x- linked * Observed in a number of conditions, including osteogenesis imperfecta (brittle bones) and duchenne muscular dystrophy

Answer 6

Genetic Multifactorial Environmental

Answer 7

* Individually rare but cumulatively enough to have regional genetic services * Down Syndrome, Cystic Fibrosis, Huntington disease, Haemophilia

Answer 8

* Main cause of disease in developed countries | * Spina bifida, Cleft lip, Diabetes, Schizophrenia

Answer 9

* Main cause of disease in 3rd world countries and A&E (genetics play a small role) * Poor diet * Infection * Drugs * Accidents

Answer 10

Chromosomes 1-22, all chromosomes except the sex chromosomes (XY)

Answer 11

The position of a gene/DNA on the genetic map.

Answer 12

Genetic constitution of an individual

Answer 13

Appearance of an individual which results from the interaction of the environment and the genotype

Answer 14

One of several alternative forms of a gene at a specific locus Normal allele is also referred to as wild type Disease allele carries the pathogenic mutation

Answer 15

Frequent hereditary variations at a locus. Doesn't cause problems (thats mutations). Polymorphisms can be you more/less efficient or make you more/ less susceptible to disease.

Answer 16

Reproductive union between two relatives

Answer 17

Homozygous by descent i.e. inheritance of the same mutant allele through two branches of the same family

Answer 18

Both alleles are the same at a locus

Answer 19

Alleles at a locus are different

Answer 20

Describes genes that are carried on an unpaired chromosome. Refers to a locus on an X chromosome in a male

Answer 21

Proportion of people with a gene/genotype who show the expected phenotype * Complete: gene or genes for the trait are expressed in all the population * Incomplete: the genetic trait is only expressed in parts of the population

Answer 22

Variation in clinical features (type and severity) of a genetic disorder between individuals with the same gene alteration

Answer 23

Expression of a particular characteristic limited to one of the sexes

Answer 24

Diseases due to a combination of genetic and environmental factors. If the condition is more common in one particular sex, the relatives of an affected individual of the less frequently affected sex will be a higher risk than relatives of an affected individual or the more frequently affected sex i.e if a boy has the condition then female relatives are more at risk and vice versa.

Answer 25

Condition not manifested at birth (where it does this is called congenital). Classically adult-onset e.g Huntington’s

Answer 26

MENDELIAN * A disease that only manifests in the heterozygous state * Affects both males and females in equal proportions. * Affected individuals in multiple generations * Transmission by individuals of both sexes to both sexes

Answer 27

* They don't have the genes for it- Gonadal Mosaicism * Mother has reduced penetrance/ variable expression *Only one defective gene is needed. (50% chance of offspring having condition with 1 affected and 1 unaffected parent) E.G. HUNTINGTONS. only way to pass on disease is from male to male, so must be autosomal dominant

Answer 28

MENDELIAN * A disease that manifests in the homozygous state * 2 defective genes required * If both parents are carriers, 25% chance of offspring having condition, 50% of offspring being carrier. * * Healthy siblings have 2/3 chance of being carriers. the affected child is disregarded in the ratio * Male and females affected in equal proportions * Affected individuals only in a single generation * Parent can be related (consanguineous)- recessive disorders most common in these types of families

Answer 29

* Most common autosomal recessive condition affecting whites in the UK * Chronic condition affecting mainly the lungs and gut, variable presentation * Incidence of 1 in 25,000

Answer 30

MENDELIAN * caused by mutation in genes on X chromosome, E.G. haemophilia and duchenne muscular dystrophy * X linked can never be passed from father to son because sons always get their X chromosome from their mother (No male-to-male transmission) * All daughters from affected male are carriers and all sons are unaffected. * All sons from affected male and unaffected female are unaffected female are unaffected * Usually males are affected, they can never be carriers * Usually transmitted through unaffected females * Examples= X linked dominant= Alport's syndrome X linked recessive= Duchenne's muscular dystrophy

Answer 31

* Process of X chromosome inactivation * One of 2 X chromosomes in every cell in a female is randomly inactivated early in embryonic development * only one functional copy of X chromosomes

Answer 32

Inactive X chromosome since packaged in heterochromatin (cannot be transcripted)

Answer 33

NON-MENDELIAN * For some genes, only 1 out of the 2 alleles is active. The other is inactive. * For particular genes it is always the paternal or the maternal allele.

Answer 34

Gene mutations may either be inherited or acquired during a person's life

Answer 35

Sporadic= 2 acquired mutations Hereditary= 1 inherited mutation + 1 acquired mutation

Answer 36

Diagrammatic form of chromosome bands, bands are numbered according to distance to centromere

Answer 37

* Chromosomal * Mendelian- Autosomal dominant/ recessive or X linked * Non traditional- Mitochondrial, Imprinting, Mosaicism

Answer 38

``` Square= Male Circle= Female Highlighted= Affected ```

Answer 39

S phase- DNA replication occurs here | Checkpoints check the DNA, mutated DNA triggers apoptosis

Answer 40

95% Nucleus | 5% Mitochondria (from ovum)

Answer 41

``` Epithelia Supporting tissues Muscle Nerves Germ cells ```

Answer 42

* One of more layers of cells that line a body cavity | * Protection, absorption, secretion

Answer 43

* Structure and protection | * Cartilage, bones, tendons and blood

Answer 44

Smooth, Skeletal, Cardiac

Answer 45

Brain, Peripheral, Visceral

Answer 46

Ova and Sperm

Answer 47

* Stains acidic things BLUE | * Stains Cell nuclei and RNA BLUE

Answer 48

* Stains alkaline things PINK * Stains cytoplasm and colloidal proteins (e.g. plasma) PINK * Stains Keratin ORANGE * Many extra cellular fibres (e.g. collagen and elastin) also stain PINK

Answer 49

Watery extra cellular jelly (GAG) and fat, so appear as white spaces

Answer 50

Stains following BLUE: * Glycosaminoglycan (GAG) rich structures (found in all connective tissue and extracellular matrix) * Mucous goblet cells * Mast cell granules * Cartilage matrix

Answer 51

Stains nuclei and elastic fibres black

Answer 52

Stains Hexose sugars (esp. those in complex carb containing structures including goblet cell mucins, cartilage matrix, glycogen, basement membranes and glycocalyx- MAGENTA (DARK PINK) Useful to detect goblet cells in SI, or GAG in intestinal brush border

Answer 53

* Stains nuclei, ribosomes, cytoplasm- DARK BLUE * Cartilage matrix, mast cell granules- PALE BLUE * GAG rich components- BRIGHT PURPLE

Answer 54

* Small cells tend to be more dormant | * Larger cells are active due to mitosis and abundance of organelles

Answer 55

* Brain of cell * Double nuclear membrane * Houses DNA 95% (in form of chromatin) within the nucleolus (site of ribosomal RNA formation. e.g. DNA transcription. Bigger it is, more metabolically active the cell) * Euchromatin- lighter areas due to different densities, decondenses sometimes (DNA needs to decondense in order to transcribe) * Heterochromatin- Darker, permanently condensed

Answer 56

* Site of oxidative phosphorylation * Double membrane, inner membrane is highly folded (cristae) * Outer membrane: lipid synthesis and FA metabolism * Inner membrane: Resp. chain (ETC), ATP production * Matrix: Tricarboxlic acid (Krebs') cycle- Cells arranged in clusters, some singletons. Chondrocytes continue to divide after solid matrix begins to form, thickened matrix restricts migration of daughter cells, so they stay in clusters * Intramembranous space: Nucleotide phosphorylation (ADP to ATP) * Contains 5% of DNA (maternal)- likely were initially bacteria that fomred symbiotic relationships with animals

Answer 57

* Site of protein synthesis | * Highly folded flattened membrane sheets

Answer 58

* Site of membrane lipid synthesis * Processes and stores synthesised proteins * Highly folded flattened membrane sheets without ribosomes

Answer 59

* Parallel stacks of membrane - processes and modifies macromolecules synthesised in the endoplasmic reticulum * Cis (first) golgi (nuclear facing - near nucleus) - receives SMOOTH ENDOPLASMIC RETICULUM vesicles, protein phosphorylation occurs here * Medial golgi (in the middle, central part) - modifies products by adding sugars - forms complex oligosaccharides by adding sugars to lipids and peptides * Trans golgi network (last, this transfers) - proteolysis of peptides into active forms and sorting of molecules into vesicles which bud from the surface * Located close to the nucleus of the cell * In most cells the golgi apparatus cannot be seen, HOWEVER it can be seen clearly in plasma cells [exam question??] - seen as perinuclear hoff (lighter area) in a plasma cell

Answer 60

Very small, spherical membrane-bound organelles which transport & store material and exchange cell membrane between compartments

Answer 61

Cell-surface derived (pinocytotic and phagocytotic vesicles) Golgi- derived transport vesicles ER - derived transport vesicles Lysosomes Peroxisomes

Answer 62

Site of breakdown for most molecules Contain digestive enzymes Derived from Golgi H+- ATPase on membrane, pumps H+ ions into cell, creating low PH to enable acid hydrolases to function Breakdown debris from dead cells and bacteria and damaged cell organelles Formed when two vesicles fuse: * Hydrolase contains enzymes that degrade proteins at low PH * Endosomes which has hydrogen atpase on membrane which pumps H+ into lysosomes to lower PH

Answer 63

Small membrane bound organelles containing enzymes which oxidase long chain Fatty acids Such as Long chain FAD-amino oxidase, catalase, urate oxidase- The above are involved in process by which FA are broken down into two- carbon fragment which the cell can use as a source for generating ATP (BETA OXIDATION) Also produce Hydrogen peroxide as byproduct of the breakdown of FA which can be used to destroy pathogens etc... (as its toxic to cells, but also peroxisomes can destroy H2O2 thus protecting body)

Answer 64

Filamentous proteins which brace the internal structure of the cell Helps maintain their shape and internal organisation They're not visible in light microscopy

Answer 65

Smallest diameter Made of Actin (Present in cells as globular Gprotein that polymerises into filamentous F actin) forming a bracing mesh (cell cortex) on inner surface of cell membrane to maintain cell shape

Answer 66

Anchored transmembrane proteins which can spread tensile force through tissues

Answer 67

Cytokeratin- epithelial cells Desmin- myocytes Glial fibrillary acidic protein (supports neurones in the brain)- astrocytic glial cells Neurofilament protein- neurones Nuclear laminin- Nuclei of all cells Vimentin- mesodermal cells They have a diagnostic utility in immunohistochemistry. Stains can show diff types of filaments, diff cells have diff types of filament

Answer 68

Tubulin (alpha and beta) arranged in groups of 13 to form hollow tubes Arise from centrosome (comprises of 2 centrioles) Found in all cells except erythrocytes (they have no nucleus, so microtubules not needed for cell division) Act as scaffold for when cells divide

Answer 69

Membrane-bound orange-brown pigment Peroxidations of lipids (degradation of lipids) in older cells Common in heart and liver, found in older people - sign of wear and tear

Answer 70

Non-membrane-bound vacuoles Appears as empty space in histology since dissolved in processing Stored in adipocytes and liver

Answer 71

CHO polymer in cytoplasm Normally seen on electron microscopy May accumulate in some cells and in some diseases

Answer 72

Technique used to stain chromosomes using Giemsa, to show visible patterned banding on karyotype. Helps to identify specific chromosomes

Answer 73

They don't grow, unless damaged (then they enter the cell cycle) Myocytes and brain cells (so with age functions less well)

Answer 74

Benign= too many cells, abnormal growth Malignant= more mitotic figures at all levels

Answer 75

Using chemotherapeutic agents to block mitosis at different stages ``` E.g. Mitotic spindle (scaffold)= Taxol ``` Spindle poles (destroy)= Ispinesib Anaphase (block)= Colchicine= like drugs

Answer 76

Thin slices Smear Thick slices

Answer 77

Preserve it by fixing in formalin (aq sol. of gas formaldehyde)- PREVENTS ROTTING Embed sample in paraffin- EXTRACTS WATER AND OTHER SUBSTANCES Very fine slices (4 microns thick) are made, mounted and stained

Answer 78

Can be difficult to imagine the 3D of a cell, because a slice can be thinner than a cell

Answer 79

To see whole cells such as blood/ other fluids/ solid tissues

Answer 80

Too hard to be a smear or slice Sample is demineralised to produce thin sections Or mineralised sections grind down to produce a thick slice.

Answer 81

Stains elastic tissue with wavy brown detail

Answer 82

Consists of 3 types of cell Stains a variety of different tissues different colours in the same section

Answer 83

Small= lymphocytes (10um DIAMETER)- nucleus, very little cytoplasm, enclosed by cell membrane. They circulate in the blood and are found in large numbers in organs such as in lymph nodes, the tonsils and the thymus gland. Many tissues also have lymph nodules full of lymphocytes within their fabric. Large= Motor neurons (70-100 um DIAMETER)= axons up to 1 metre

Answer 84

Rounded- e.g. biconcave discs Polygonal- Irregular shaped cells Fusiform- Elliptical shaped Squamous- E.g. Fibroblasts Flattened, appear to have thin plates, cells towards centre of cell of polygonal and mature into squamous cells Cuboidal- E.g. Thyroid, roughly square Columnar- E.g. cells lining gallbladder, more rectangular

Answer 85

Dormant cells are generally smaller, as they don't need to maintain an elaborate cellular mechanical machinery. When challenged, they differentiate further increasing the amount of cytoplasm and become more metabolically active. Metabolically active cells often have a nucleoli, and have an abundance of cellular organelles so are larger

Answer 86

Days- Lining of the SI (gut) (4-5 days) Months- Lots of tissues- blood (120 days), skin, connective tissue Years- Bones and tendons Nearly whole life- (limited regeneration) skeletal muscle Whole life- Nerves and brain, cardiac muscle, stem cells and germ cells (almost no capacity to regenerate)

Answer 87

Interstitial fluid: * Water * Salts in solution * Peptides and proteins (e.g. plasma proteins, hormones etc.) Extracellular material: * Fibrillar proteins- e.g. collagen, elastin, or tendons * GAG jelly * Inorganic salts as solids (e.g. calcium in bone)

Answer 88

CHONSP ``` Carbon Hydrogen Oxygen Nitrogen Sulfur Phosphate ```

Answer 89

* Made of one or more cells * Capable of reproduction * Responding to the environment * Adapting and changing * Requiring a source of energy * Growing and or developing

Answer 90

Atoms are the simplest levels Two or more atoms make a molecule Macro molecules are large, biologically important molecules inside cells Organelles are aggregates of macro molecules used to carry out a specific function in the cell ORGANELLES, CELLS, TISSUES, ORGANS, ORGAN, ORGAN SYSTEM AND ORGANISM

Answer 91

Simple molecules such as sugars, lipids and amino acids, can form complex large molecules They have osmotic, structural, optical, enzymatic and other complex functions Examples include: Haemoglobin, DNA, glycogen, rhodopsin and collagen Structures of macromolecules are very heterogenous

Answer 92

Monosaccharide to Polysaccharide with glycosidic bond Nucleotide to Nucleic acid with phosphodiester bond Amino acid to Protein with peptide bond

Answer 93

General formula: Cn(H20)n | E.g. monosaccharides, disaccharides, oligosaccharides, polysaccharides

Answer 94

Lactose Sucrose Maltose

Answer 95

Chain of carbons, hydroxyl groups and one carbonyl group An aldose has an aldehyde A ketose has a ketone group

Answer 96

Carbon with 4 different groups attached D & L monosaccharides have the same chemical properties but different biological ones (isomers) There will be Two optically active and different forms Most sugars living in organisms are D, when not indicated its the D form Under polarised light- D shifts it right, L shifts it left

Answer 97

By the reaction of the aldehyde or ketone groups with a hydroxyl group of the same molecule, monosaccharides generally exist as ring structures. There are chair forms, zig-zag. Don't lie on same plane

Answer 98

The hydroxyl group of a monosaccharide can react with an OH or an NH group to form a glycosidic bond. O- glycosidic bonds- (oxygen i.e. hydroxyl) form disaccharides, oligosaccharides and polysaccharides N- glycosidic bonds- (nitrogen i.e. amine (NH) are found in nucleotides and DNA Alpha- hydroxyl groups on the same side

Answer 99

Aminosugars: containing an amino (NH2) group. Often acetylated. e.g. Glucosamine Alchohol- sugars. e.g. Sorbitol Phosphorylated: containing Phosphate groups, e.g. G6P Sulfated: Sulfate groups, e.g. Heparin chondroitin sulphate

Answer 100

Disaccharides contain 2 monosaccharides (MS) joined by an O-glycosidic bond. Oligosaccharides contain 3-12 MS. Oligosaccharides are the product of digestion of polysaccharides, or part of complex protein/lipids

Answer 101

Formed by thousands of MS joined by glycosidic bonds e.g. Starch - storage in plants, made of amylose (glucose alpha 1,4) and amylopectin (glucose alpha 1,4 and alpha 1,6 glycosidic bonds) Proteoglycans

Answer 102

Long, unbranched polysaccharides radiating from a core protein [found in animals]

Answer 103

GLYCOGEN - storage in animals, is a branched polysaccharide formed of glucose residues. Linkage is both alpha 1,4 (between carbons) and alpha 1,6 (between side chain and main chain) - branching is at regular intervals. Core protein is glycogenic, amino linked to the only reducing end of the inner chain

Answer 104

Triglyceride= 3 FA bound to glycerol Straight carbon chains (mostly 16-20) with a methyl group (CH3) and a carboxyl gorup (C=OOH) at the ends. Melting point decreases with the degree of unsaturation (fluidity). Some of the C-C bonds can be unsaturated (i.e. have double bonds) tend to be hydrophobic and contain no oxygen in main chain. In unsaturated FA, double bonds are commonly cis and spaced at 3C intervals Many natural sources and many functions. Such as cooking oils

Answer 105

Cholesterol is a naturally occurring fat

Answer 106

Derivatives of Arachidonic acid. Synthesised from 20 C atoms Major biological functions,metabolised to form prostaglandin, thromboxane etc... Cell signalling molecules

Answer 107

Building blocks of DNA, Made from Nitrogenous base, sugar and phosphate In DNA= * Adenine- thymine (2 CARBON NITROGEN RINGS=Purines), * Cytosine- guanine (1 CARBON NITROGEN RING=Pyrimidines) * Deoxyribose sugar In RNA= * A-U * C-G * Ribose sugar

Answer 108

Between bases= hydrogen bonds Between phosphate and sugar are phosphodiester bonds Phosphate bonds in nucleotides are a source of energy Nucleotide has N-glycosidic bond between base and sugar, and Ester bond between Phosphate ester and sugar

Answer 109

Building blocks of proteins- 20 in total Carbon with amino group, carboxyl group and side chain Charge is determined by all three components. charge changes somewhat with the PH of the solution Side chain often determines polarity (hydrophillic) non polarity (hydrophobic) of the amino acid E.g glutamic acid- net negative charge since two carbon groups, 1 amino group Carboxyl groups= negative Amino group= positive Most natural amino acids are in the L form, in contrast to that of sugar whose natural form is D At different PH carboxyl and amino groups are ionised (charged). Some amino acids also have ionisable side chains (can associate and dissassociate)

Answer 110

Formed by condensation reaction (water released) between carboxyl group and amino group Amino group first then carboxyl group at the end Protein are formed by linked amino acids which are bonded together by peptide bonds These linear chain fold in different shapes to form 3D structures

Answer 111

Charged interactions, flexibility and physical dimensions Sequence of amino acids, also determines folding and structure

Answer 112

Very stable cleaved by proteolytic enzymes Cleaved (broken down bye) by proteolytic enzymes or extreme temperatures- Proteases or peptidases Can have partial double bonds Flexibility around C atoms not involved in bond thus allows multiple conformations There is usually one preferred confirmation (i.e. R1 AND R2 (residual group) on the same side of chain or on different side) determined mainly by the type of side chain and their sequence in the polypeptide

Answer 113

Large polypeptide usually formed from 10s to 1000s of amino acids Functions is totally dependent on structure (huge variety of functions arise from huge number of different shapes) Function is dependent on structure

Answer 114

Protein= functional and synthesised by a cell (50= AA) Peptide= Bit of protein broken off (less than 50 AA long)

Answer 115

Linear sequence of amino acids, held together by covalent bonds Sequence of AA in protein determine where bonds will form thus structure and thus function

Answer 116

Formation of either alpha helix (H-bonds between each carbonyl group and the H attached to the N which which is 4 AA along the chain. Side chains look outwards. Proline breaks the helix (ring + no H) Or beta pleated sheets (formed by H bonds between linear regions of polypeptide chains, chains from 2 proteins or same protein, if the chain is folding back, structure is usually a 4 AA turn, called a hairpin loop or beta turn due to hydrogen between amino acids- determined by a local interactions between the side chains and sequence of AA ``` Super- secondary structures: Combination of secondary structures. Structures and functional units of folded proteins often consists of combinations of alpha and beta structures= Helix-turn-helix B a B unit Leucine zipper zinc finger ```

Answer 117

Overall 3D confirmation of a protein Bonding involved is electrostatic, H bonds and covalent bonds. Folding of the secondary structure into a globular structure due to bonds such as ionic bonds, disulphide bridges and Van der Waal forces. Confirmation can change with temperature or pH.

Answer 118

3D structure of protein composed of multiple subunits. Same non- covalent interactions as tertiary structures. 2 or more tertiary structures joined together to form a protein e.g. haemoglobin

Answer 119

Van der waals Hydrogen bonds Hydrophobic forces Ionic bonds Disulphide bonds

Answer 120

Weak/attractive force between all atoms due to fluctuating electrical charge- only important when 2 macromolecular surfaces fit closely in shape. Can also be repulsive at very short distance

Answer 121

Weak interaction between polar bonds (dipoles). IMPORTANT IN AMINO ACID SIDE CHAINS, oxygen and nitrogen in main chain and water Partial negative charges on negative atoms, O and N. Partial positive charge on H

Answer 122

As uncharged and non-polar side chain are repelled by water, these hydrophobic side chains tend to form tightly packed cores in the interior of proteins, excluding water molecules. This attraction is the 'hydrophobic force'

Answer 123

Between fully partiallly charged groups. Weakened in aqueous systems by shielding by water molecules and other ions in solution

Answer 124

Very strong covalent bonds between sulphur atoms Lots of Cysteine= stronger stability, cell surface receptors, antibody

Answer 125

``` Temperature PH Conc. of reactants Catalyst Surface area of a solid reactant Pressure of gaseous reactants or products ```

Answer 126

Powerful biological catalyst Enzymes bind the reactants (substrates) and convert them to products. Then they release the products and return to their original form Not only they speed-up the reactions, but provide a way to regulate the rate of reactions Can be used for diagnostic purposes because since they control metabolism they can be used as disease markers e.g. when released in bloodstream, when they should be present. A lot of drugs work by inhibiting the actions of enzymes

Answer 127

Enzymes can be regulated by altering the concentration of substrates, products, inhibitors or activators, they can also be regulated by modifying the enzyme itself by phosphorylation.

Answer 128

Enzyme that have a different structure and sequence but catalyse the same reaction

Answer 129

As T increases, the stability of the enzyme structure decreases- bonds weaken, eventually leading to denaturation and thus lower reaction speed

Answer 130

They cannot in them self catalyse a reaction but can help enzymes to do so. They can bind with the enzyme protein molecule to form the active enzyme Complex organic structures which help to maximise the repertoire of enzymes functional groups, they can be metal ions (Fe 2+, Mg 2+, Zn 2+) or organic (usually derived from vitamins) or both (e.g. Fe 2+ and heme) Activation-transfer coenzymes Oxidation-reduction enzymes

Answer 131

Form a covalent bond and are regenerated at the end of the reaction

Answer 132

Involved in reactions where electrons are transferred from one compound to the other. E.g. NAD + transfers electrons with hydrogen and is important in energy processes including the generation of ATP.

Answer 133

Haemoglobin- found in red blood cells, oxygen carrier in blood Myoglobin- found in muscle, serves as a reserve supply of oxygen and also facilitates the movement of O2 in muscles Both Haemoglobin and myoglobin are structurally related proteins with some common elements- have the same tertiary structure At the core of both molecules

Answer 134

Porphyrin ring which holds an iron atom. An iron containing porphyrin is termed a heme. This iron atom is the site of oxygen binding- the name haemoglobin in the combination go heme and globin. Thus haemoglobin can be regarded as an enzyme that binds and releases o2 thus Fe can be seen as a coenzyme since its the site of o2 binding (when o2 binds, haemoglobin molecule changes shape slightly)

Answer 135

Partial pressure of o2 in blood, as it increases so does haemoglobin saturation Temperature, H+ and partial pressure of CO2 (PCO2)= all modify the structure of haemoglobin and alter its affinity for O2. Increase in these results in; haemoglobin decreased affinity for O2 and enhanced unloading of O2 from the blood. Decrease acts in opposite manner. All these parameters are high in peripheral capillaries where O2 unloading is the target Sickle cell anaemia Genetic disorder that is characterised by the formation of hard, sticky sickle shaped red blood cells

Answer 136

Antibodies Main function is to bind to antigens on toxins and proteins. these targets are consequently labelle dfor destruction by cells of the immune system by lysis or thorugh complement system Many different types : IgG, IgM, IgA. Antibody- antigen binding is very specific- one antibody only matches one antigen Antigens are bound by a portion of the antibody called the variable domain (THUS SPECIFICITY OF ANTIBODIES DETERMINED BY THE VARIABLE REGION). Amino acid in the variable domain can be varied to produce a potentially infinite variety of 3D shapes to recognise an infinite variety of foreign antigens

Answer 137

Disulphide bonds define loops characteristics of Ig Light chains, heavy chains Variable regions have light chains and heavy chains (Vl, Vh) and constant regions (Cl, Ch) Specific antigen binding sites and bind to other antibodies

Answer 138

Less compartmentalisation No nuclear membrane DNA arranged often in single chromosome In E. Coli it is circular

Answer 139

More compartmentalisation DNA is in the nucleus, bound to proteins (chromatin complex). Different appearance according to functional moment e.g. looks large and dark in mitosis since chromatin condense into visual aggregates- CHROMOSOMES Each chromosome is made of 2 identical strands of (chromatids) joined in teh centre (centromere). some DNA is found in mitochondria (purely maternal DNA)

Answer 140

DNA in physiology: DNA, RNA, protein DNA in pathology: Genetic disease, viruses, cancer DNA in diagnostics: Mutation analysis, microbiology, forensic medicine DNA in therapy: DNA as drug target, gene therapy, risk assessment DNA in biotechnology: Production of biomedicines, delivery vectors, gene products

Answer 141

DNA is a template and regulator for transcription and protein synthesis. DNA is the genetic material thus the structural basic of hereditary and genetic diseases.

Answer 142

Nucleotides are the building blocks to make new DNA Free phosphate groups provide energy for the reaction to go through

Answer 143

DNA polymerase reads the template strands from 3' to 5' thus DNA is synthesised on the daughter strand from 5' to 3' since DNA runs antiparallel, the daughter strand is synthesised from 5' to 3' since phosphate at the 5' is used by enzyme as a source of energy for reaction to occur (ACTIVATION ENERGY)- reason why DNA CAN ONLY BE SYNTHESISED FROM 5' to 3' From diagram , at one end of the molecule is an unreacted oxygen (3’) whereas at 5’ end there is a phosphate group thus DNA can only be synthesised from 5’ to 3’ since if it was 3’ to 5’ there would be no phosphate group available to provide the energy for the reaction to occur Unreacted oxygen at 3’ thus DNA polymerase must start at 5’ with phosphate as energy source DNA strands run antiparallel to each other i.e one runs 5’ to 3’ whereas the other runs 3’ to 5’

Answer 144

Topoisomerase: Unwinds the double helix by relieving the supercoils DNA helicase: Separates the DNA apart, by breaking hydrogen bonds between bases, exposing nucleotides DNA polymerase: Reads 3’ to 5’ and synthesises DNA on daughter strand 5’ to 3’ - creates DNA by working in paris to make 2 new strands of DNA. Starts at a primer Primer- short strand of DNA that is the start point for DNA synthesis as DNA polymerases can only add nucleotides on to an existing strand of DNA Single strand binding protein (SSB) - keeps two strands of DNA apart whilst synthesis of new DNA occurs - prevents annealing to form double stranded DNA Primase enzyme: RNA polymerase that synthesises the short RNA primers needed to start the strand replication process RNAse H: removes the RNA primers that previously began the DNA strand synthesis

Answer 145

1. Prior to cell division, topoisomerase unwinds DNA and DNA helicase separates DNA apart to expose two single DNA strands and create two replication forks. DNA replication takes place simultaneously at each fork. 2. SSB’s (single-strand binding protein) coat the single DNA strands to prevent re- annealing or ‘snapping back together’. 3. The primate enzyme then uses the original DNA sequence on the parent strand to synthesise a short RNA primer. Primers are necessary since DNA polymerase can only extend a nucleotide chain, not start one 4. DNA polymerase begins to synthesise a new DNA (via complementary base pairing using free floating nucleotides) strand by extending an RNA primer in the 5’ to 3’ direction. Each parental strand is copied by one DNA polymerase. 5. As replication proceeds, RNAse H recognises RNA primers bound to the DNA template and removes the primers by hydrolysing the RNA 6. DNA polymerase can then fill the gap left by RNAse H 7. DNA replication process completed when the ligase enzyme joins the short DNA pieces (Okazaki fragments) together into one continuous strand.

Answer 146

(Single stranded unlike DNA which is double stranded) mRNA (messanger) rRNA (ribosomal) tRNA (transfer) Unlike DNA, aren't present in the cell at all times Many mRNA species only accumulate following cell stimulation

Answer 147

Proteins that bind to promoter regions find their way to specific sequences on the 5' of the 1st exon (region called the promoter) Promoter has a specific sequence of nucleotides- they do not code fro proteins but instead act as binding sites- found at the 5' end Transcription complex forms around the TATA box (reads thymine, adenine, thymine, adenine etc...) on the 5' axon of the 1st exon

Answer 148

Topoisomerase unwinds double helix, relieving the supercoils DNA helicase then separates the DNA apart exposing nucleotides SSB's coat the single DNA strans to prevent DNA re-annealing Free mRNA nucleotides line up next to their complementary bases on the template strand (U-T & C-G) RNA polymerase (specifically RNA polymerase 2) joins the mRNA nucleotide (catalysing phosphodiester bonds between them to form an antiparallel mRNA strand (5' CAP head and a 3' Poly A tail starting at a promoter (specific sequence that RNA polymerase binds to- initiation of transcription. Transcription is stopped at the stop codon) mRNA leaves the nucleus and attaches to an 80s ribosome At ribosome the mRNA (bases on mRNA are read in 3- codon) sequence is used as a template to bind to complementary tRNA molecules at their anticodon (3 bases complementary to codon on mRNA). Ribosome reads mRNA codon by codon, one codon will code for a particular amino acid. This amino acid is brought by a specific tRNA molecule (carried on it 3’ end) since tRNA molecules are attached to specific amino acids. BASES ARE READ 5’ TO 3’ Enzymes remove amino acid from tRNA and amino acids are linked together by a peptide bond (created by a condensation reaction), creating a polypeptide chain - a protein

Answer 149

``` Heat denaturation (melting T) (outside DNA) Alkali dissociation (outside of humans) Hybridisation (the longer the strands become the easier it is to separate using enzyme Helicase) ```

Answer 150

Prior to cell division DNA opens at the replication fork. Base sequence on each parent strand is copied into a complementary daughter strand. The two parental strands separate in front of the fork. New DNA is made behind the fork, composed of a new and an old strand: replication is semi conservative. Many proteins are involved in DNA replication, binding proteins and enzymes.

Answer 151

A binding protein (DNAa) starts the process at a single point of origin (oriC) The parental strands separate, and form a bubble. Both strands are copied simultaneously and in opposite direction. Sequences are proof-read. Replication ends at a termination point. DNA is circularised by ligases. Cell division

Answer 152

DNA polymerase reads 3’ to 5’, prints 5’ to 3’ Substrates are deoxyribonucleotides triphosphates Enzyme stays on the strand, at the same times extends and proof-reads

Answer 153

Helicase opens the strand SSb protein keeps it open Topoisomerase unwinds it (relieves supercoil)

Answer 154

One strand is done normally 5' to 3' | The other strand is done using Okazaki fragments which are joined together by ligase

Answer 155

DNA damage: chemicals, UV, radiation, chance DNA repair: base or nucleotide excision mismatch repair transcription-couple repair

Answer 156

DNA replication in test tube Isolate DNA and use heat stable DNA polymerase with primers to amplify DNA Using heating and cooling

Answer 157

Printed as a long linear transcript Processed to the mature form (in proximity of the nuclear membrane). It has a 5' CAP and a 3' Poly A tail Ribosomes are abundant in eukaryotic cytoplasm, and four main types of rRNA combine with proteins to form 80s ribosomes

Answer 158

Ribosomes print transcript mRNA with help from transfer RNA

Answer 159

tRNA carry aminoacids to ribosomes, and check that they are incorporated in the right position. Each tRNA only carries one aa >>> at least 20 tRNA types Very small molecules At the anticodon, a triplet sequence pairs with mRNA >>> right aa for the right triplet ( = CODON).

Answer 160

``` START= AUG STOP= UGA, UAG, UAA ```

Answer 161

Primary transcript, mRNA is made in the nucleus from DNA after signals that protein synthesis is needed Leaves the nucleus via nuclear pore where it is edited to PolyA-RNA, mRNA Ribosome (RER) recognises mRNA from its CAP on the 5’ end Ribosome is responsible for translation VIA tRNA carry AA Polypeptide is formed , edited in Goglgi apparatus to form final protein product

Answer 162

Exons contain the coding sequence. Introns are non coding Promoter region is what RNA polymerise recognises and where it starts mRNA primary transcript - mRNA strand is a complementary copy of original DNA Primary > Mature - Non-coding (introns) are removed and exonic regions are joied

Answer 163

Exon shuffling (where exons are not in the same order) allows new proteins to be made e.g. the immune system. Thus exon shuffling enable huge variants of antibodies etc... to be produced

Answer 164

Degenerate but ambiguous- Many AA specified by more than one codon, but each codon specifies only 1 AA Almost universal- all organism uses same code- fewer that 10 exception Non overlapping and without punctuation- codons don't overlap. each nucleotide is only read once

Answer 165

tRNA contains an aminoacid | at its 3’ end corresponding to the codon on mRNA to which the anticodon of the tRNA can base pair.

Answer 166

Protein called 'transcription factors' find their way into specific sequences 5' of the 1st exon (region called 'promotor') A transcription complex forms around the TATA box 5' of the 1st exon Hellix opens, DNA strand separation RNA pol 11 starts building mRNA etc....

Answer 167

Activation of repressors (inhibitors of RNA polymerase binding) Each step of RNA transcription or processing finds no longer actively produced transcription and processing proteins. Complexes do not form anymore for lack of phosphorilation. Enzymes no longer activated RNA stability Many other unknown mechanisms

Answer 168

DNA can be chemically altered to the methylated form i.e turned on or off (silenced) In a macrophage, where immunoglobulins are not produced, but still has normal DNA, the gene for producing immunoglobulins will be in the heterochromatin (can remember as h = hiding i.e. not active) state - since its not needed to be synthesised thus in the heterochromatin state no transcription of these gene can occur Whereas in a B cell, that needs to produce immunoglobulins, that gene will be in the euchromatin state - so it can be transcripted and thus immunoglobulins (proteins) can be synthesised z

Answer 169

Duplications of genes or part of a gene (of a single base or whole gene) Deletions (whole gene or some exons)- Inframe, or out of frame Mutations of regulatory sequence (coding sequence still intact, but gene itself is switched on or off etc...) DNA damage: from chemicals, UV, and radiation DNA repair issues: Base nucleotide excision, mismatch repair or transcription- coupled repair Mis-sense mutation Non- sense mutation Splice site mutation Expansion of a Tri-nucleotide repeat

Answer 170

Can be an in frame deletion- whereby a complete codon is removed thus only 1 AA is lost. This is less catastrophic. Known as in frame deletion since the reading frame is not altered. Results is a milder disease- later onset death typical

Answer 171

Can be out of frame deletion which clearly disrupts the protein e.g. deletion causing the absence of dystrophin in duchenne muscular dystrophy. If C is lost the sequence shifts to the right once, so the reading frame is changed. Can cause quite catastrophic effects- early mortality

Answer 172

A point mutation in which a single nucleotide change results in a codon that codes for a different amino acid (substittion). This can have varied affect and can result in a silent mutation and a non functional protein. e.g. Sickle cell disease where CAG is replaced by CTG May or may not be pathogenic could be a polymorphism or of no functional significance

Answer 173

Point mutation that produces a stop codon - results in an incomplete, usually non-functional protein. E.g. Duchenne’s muscular dystrophy

Answer 174

Affects the accurate removal of an intron Enzyme recognises CGAT as cutting site. A changes to C and then enzyme no longer recognises the sequence, so excision doesnt occur thus sequence of intron is translated and proteins are synthesised

Answer 175

Huntingtons disease= CAG Triple repeat is repeated several times in the first part of the coding sequence. The normal rnage of repeats is 15-20 If repeats are larger than 36, the patient will develop Huntington's. If repeats is larger, onset will be earlier. If repeats is less that 36, then no disease

Answer 176

In diseases such as Huntington’s, repeats get bigger when they are transmitted to the next generation resulting in earlier symptoms of greater severity - this process is called anticipation

Answer 177

``` Polymerase chain reaction To synthesise fragments of DNA Its the basis for forensic testing Uses primers: short synthetic pieces of DNA that have complementary bases to DNA you are trying to synthesise/amplify One cycle takes 5-20 mins ```

Answer 178

Only one allele functioning. Most loss of function variants are recessive. If a pathway is very sensitive to the amount of gene product so that if only half is produced it cannot function this will cause a problem. Haplo-insufficiency

Answer 179

Increased gene dosage e.g. PMP22 duplication on 1 allele in hereditary motor and sensory neuropathy type 1A Increased protein activity e.g. a variant may occur at the recognition site for protein degradation leading to an accumulation of undegraded protein within the cell

Answer 180

Where the protein from the variant allele interferes with the protein from the normal allele. E.g. a dimer where one variant and one normal allele would result in only 25% normal dimers

Answer 181

Patient has signs and symptoms suggesting a particular diagnosis A molecular genetic test will confirm a diagnosis In this context a genetic test is being used to confirm a clinical diagnosis Issues informed consent

Answer 182

Testing health at-risk family members for a previously identified familial variant – often dominant HD No intervention BRCA1/2 some intervention

Answer 183

Autosomal recessive and X-linked disorder Testing an individual in isolation not particularly helpful – couple testing Reproductive decision making

Answer 184

Genetic test performed in pregnancy where there is a increased risk of a specific condition affecting the fetus Chorionic villous sample or amniocentesis Often chromosomal or DNA if specific variant in the family has been identified Counselling issues

Answer 185

8 cell embryo Under gentle suction pipette removes one cell Single cell free for analysis

Answer 186

Target population, not high risk families E.g. Newborn screening for Cystic fibrosis It may be the same test but the context is different

Answer 187

Increased or decreased risk for a multifactorial condition This issue is only just emerging

Answer 188

Testing for genetic conditions – offered in Clinical Genetics * Diagnostic * Carrier * Predictive * Prenatal tests incl. NIPT Testing to clarify familial relationships – usually done in private sector or a forensic laboratory * Paternity testing Genetic testing to determine identity – usually done in a forensic laboratory * Genetic finger printing

Answer 189

Fluorescence in situ hybridisation DNA probes labelled with fluorophores They are hybridised directly to the chromosome preparation or interphase nuclei You can count the chromosomes in interphase, look for submicroscopic deletions using locus specific probes, interpret abnormalities more clearly, we can look for specific rearrangements such as gene fusions etc, in acquired abnormalities FISH is routine and can provide quick results without the need to look at chromosomes or provides more “detailed” information.

Answer 190

Used to look at chromosomes both constitutionally and as acquired changes. Confirm malignancy, classification of a disease type, prognosis, monitoring Constitutional changes occur at gametogenesis, affects all cells of body and are heritable. These changes are associated with abnormal mental and physical abnormality in the patient. Acquired changes occur during lifetime, restricted to malignant tissue, not heritable.

Answer 191

Breakpoints occur in two genes and fuse to form hybrid gene Translocation gene

Answer 192

New technology that improves the resolution for detecting cytogenic abnormalities

Answer 193

Tubulin Microtubules are tubular polymers of alpha- and beta-tubulin and have a diameter of 25nm. Actin is a microfilament, 5nm in diameter Cytokeratin, desmin and vimentin are all intermediate filaments

Answer 194

Anaphase This is a description of anaphase, during which the chromosomes are pushed to either pole of the cell. The nuclear membrane forms around the nuclear material in telophase.

Answer 195

Vagina ``` The skin (keratinised), oral cavity, tongue, oesophagus and vagina (non-keratinised) are all lined by stratified squamous epithelium. The trachea is lined by a pseudostratified columnar epithelium (respiratory epithelium) The duodenum is lined by a simple columnar epithelium. The pleural cavity is lined by a simple squamous epithelium (mesothelium). The ureter is lined by a complex epithelial type known as urothelium. ```

Answer 196

Bronchus Cilia are microscopic motile projections on the luminal surface of some epithelial cells. They function to move material across the surface of the epithelium. Cilia are found on the epithelial cells lining the fallopian tubes and conducting airways. Do not confuse them with microvilli, which are present on cells lining the gut. Microvilli serve to increase surface area for absorption. Renal tubules are lined by non-ciliated cuboidal cells. The urethra is lined by non-ciliated urothelium.

Answer 197

Glycogen Simple molecules such as sugars, amino acids and nucleotides can join together to form large complex macromolecules. Examples of macromolecules include DNA, glycogen, haemoglobin, rhodopsin and collagen. Glyceraldehyde is a 3-carbon carbohydrate (that you will meet again in glycolysis) Lysine is a positively-charged amino acid Adenine is a nitrogenous base Adenosine triphosphate is a nucleotide

Answer 198

Beta pleated sheet In amyloidosis, proteins are deposited in tissues in a beta-pleated sheet conformation. This is an example of a secondary protein structure (the alpha helix is the other.) The linear chain is a protein’s primary structure. Beta-alpha-beta units, helix-turn-helix conformation and zinc fingers are all supersecondary protein structures.

Answer 199

Adenine: Thymine In DNA, Adenine always pairs with thymine and guanine always pairs with cytosine. Adenine does not pair with itself! The distractor was option E – adenine DOES pair with uracil, but in RNA, not DNA! (There is no uracil in DNA.)

Answer 200

Locus heterogenity An allele is one of a number of alternative forms of the same gene found at the same genetic locus. Hypertrophic cardiomyopathy is an example of a disease with locus heterogeneity – mutations in different genes give the same clinical condition. Allelic heterogeneity (also known as mutational heterogeneity) is when lots of different mutations in one gene cause a condition (such as cystic fibrosis). Allelic homogeneity is when all individuals with a disease have the same mutation (e.g. Huntingtons). Allelic polymorphism is when more than one allele can be found for a given gene within the normal population. Expansion of tri-nucleotide repeats is found in conditions such as Huntingtons, Myotonic dystrophy and Fragile X syndrome.

Answer 201

Autosomal dominant

Answer 202

Females with Turner syndrome The normal karyotype is 46, XX for females and 46, XY for males. The karyotype 45, X denotes a female lacking one of the two X chromosomes. This is Turner syndrome. A female with Down syndrome would have the karyotype 47, XX, +21 (as Down syndrome is due to trisomy 21) A female with Edwards syndrome would have the karyotype 47, XX, +18 (as this is due to trisomy 18).

Answer 203

X linked inheritance Recessive mutation Female carriers Males with one copy of the gene are affected

Answer 204

They affect males and females in equal proportions Autosomal recessive diseases occur with equal frequency in males and females. (Unlike X-linked which are more common in males) Homozygotes have the disease, while heterozygotes are asymptomatic carriers of the mutation. (Unlike dominant diseases, which occur in homozygotes and heterozygotes) Consanguinuity (reproductive union between related individuals) increases the risk that offspring will have an autosomal recessive disease. However, autosomal recessive diseases can manifest in any family (irrespective of race). Typically, when the pedigree is constructed, the disease has manifested in only one generation of the family.

Answer 205

By clinical observations: Family studies- In a multifactorial condition, risk of condition in relatives of an affected individual is dramatically higher than in the general population. Risk varies with degree of genetic relationship, risk varies with severity and number of relatives affected. Twin studies- compare Genetically identical and non identical twins. Higher risk in genetically identical twins Adoption studies- Adopted children of a parent with a multifactorial condition have high risk of developing the disease. Low risk of adoptees and normal biological parents. Higher in biological families

Answer 206

Maintenance of constant internal environment Property of a system in which variable are regulated so that internal conditions remain stable and relatively constant E.g. Temperature, Blood pressure, PH, glucose and oxygen concentration Cells must communicate with each other to achieve homeostasis, major communication systems include: endocrine (hormones), nervous (currents and neurotransmitters) and immune (antibodies, cytokines and interleukin_

Answer 207

Chemical is released from cell into the extracellular fluid and then acts upon the very cell that secreted it Cell talking to themselves

Answer 208

Chemical messengers involved in the communication between cells, released into extracellular fluid - travel short distances, local communication. E.g Acetylcholine at neuromuscular junction Cell talking to neighbouring cells a short distance away

Answer 209

Secretion into blood Produce and secrete hormones, communication between cells, travel much longer distance, systemic communication, can affect the whole body. E.G. acetylcholine at neuromuscular junctions

Answer 210

Secretion into ducts then into organ | Cells talking to other cells elsewhere in body

Answer 211

Hormones travel in blood in endocrine whereas in paracrine chemical messangers only travel in extracellular fluid. Endocrine affects more things and travel further than paracrine

Answer 212

Amplification of signal. E.g. clotting cascade & oxytocin release during childbirth

Answer 213

Centre of homeostasis, main way endocrine hormones are controlled. E.g. blood sugar regulation, temperature regulation, blood pressure regulation, thyroid regulation - thyroxin, as well as going to target cell, is also sensed by the pituitary, if there is too much thyroxine in the blood then the high thyroxine levels will stimulate the pituitary to stop producing thyroid stimulating hormone (TSH)

Answer 214

Can get primary hypothyroidism: that is the thyroid is producing too little thyroxine to induce negative feedback, meaning TSH levels in the blood keep increasing since pituitary doesn't think there is enough thyroxine in the blood. Can also get primary hyperthyroidism: whereby the thyroid produces too much thyroxine and keeps producing regardless of the presence of TSH produced by the pituitary, TSH levels fall but thyroxine levels rise. Primary - means the problems is with the endocrine gland e.g. the thyroid. Secondary - means the problem is with the pituitary or hypothalamus e.g secondary hypothyroidism - whereby both TSH and thyroxine levels are low (indicative of secondary hypothyroidism) since the pituitary is not producing enough TSH thus little thyroxine is produced meaning target cells are not being induced.

Answer 215

Organs involved: Hypothalamus (hypothalamic hormones include dopamine) Pituitary (anterior pituitary hormones and posterior pituitary hormones include oxytocin and ADH/ vasopressin) Thyroid (front of neck), Parathyroid (directly behind neck) Adrenals (above kidneys) Pancreas Ovaries Testes

Answer 216

Gonadotrophin-releasing hormone (GnRH) Growth hormone-releasing hormone (GHRH) Somatostatin (SS) Thyrotropin-releasing hormone (TRH) Corticotropin-releasing hormone (CRH) Dopamine (DA)

Answer 217

* Folicle stimulating hormone (FSH) * Lutenising hormone (LH) (TWO ABOVE ARE GONADOTROPHIC HORMONES) * Growth hormone (GH) * Thyroid stimulating hormone (TSH) * Prolactin * Arendocorticotrophic hormone (ACTH)

Answer 218

``` Oxytocin- released during child birth Antidiuretic hormone (also known as Vasopressin, ADH)- (in brain, master endocrine organs), ```

Answer 219

Moleucle that act as a chemical messanger Classifies according to structure: Peptide, amino acid derivatives (from tyrosine/tryptophan), Steroid (from cholesterol)

Answer 220

Made from short chain amino acids, vary in size from few amino acids to small proteins, some have carbohydrate side chains (glycoproteins) They are large, hydrophilic charged molecules that cannot diffuse across a membrane. They bind to receptors on membranes. Peptide hormone is pre-made and stored in cell, then released and dissolved into blood when needed. Binds to receptor on membrane then chemical reaction produces a quick response from the cell and a 2nd messenger is released in the cell - VERY FAST (minutes) (signal transduction cascade). Examples; Insulin, growth hormone, thyroid stimulating hormone (TSH) and ADH/vasopressin

Answer 221

Synthesised from tyrosine, acts in same way to peptide. Examples; adrenaline, thyroid hormones (thyroxine (T4) and triiodothyronine (T3))

Answer 222

Synthesised from cholesterol,water insoluble & lipid soluble - can cross membranes BUT requires transport proteins in blood, targets an intracellular receptor. Steroid hormone is made by cell and diffuses out once made (not stored), transported in blood bound to transport proteins as it cannot dissolve in water. Binds to receptor inside cell. SLOW RESPONSE (hours/days) since it directly affects DNA. Examples; Testosterone, oestrogen and cortisol (long term stress hormone)

Answer 223

Total body water= 60%, 42L ICF= 40% of body weight, 28L ECF= 20% of body weight, 14L Intravascular= 3L Interstitial= 11L

Answer 224

Predominant electrolyte is potassium

Answer 225

Predominant electrolytes are sodium (main contributor to ECF osmolarity and volume), chloride and bicarbonate (anions) and Ca2+ (especially in heart and muscle), protein= colloid osmotic pressure, glucose and urea especially in heart and muscle

Answer 226

Surrounds the cells, but doesn't circulate

Answer 227

Circulates as the extracellular component of blood Change in plasma osmolality pulls or pushes water across cell membranes

Answer 228

Makes up the CSF, digestive juices and mucus

Answer 229

Osmotically active substances (solutes)= Potassium, sodium, chloride, glucose and urea If there is any change in the solute continent of a compartment- there is a shift in water Always equal= isotonic Any change in solute content of a compartment= Shift in water

Answer 230

Drink, diet, IV fluid

Answer 231

Kidneys | Insensible losses: sweat, breath, vomiting & faeces

Answer 232

It is hypo-osmolar/hypotonic vs cells Water enters blood cells causing them to expand and burst: haemolysis However, this only occurs in the vicinity of the intravenous cannula If you could achieve instantaneous mixing it wouldn’t occur

Answer 233

Tightly regulated Changes in ECF osmolality lead to a rapid response Water deprivation or loss will lead to a chain of events Water deprivation/increased in solutes= Increased ECF osmolality : * Change detected by osmoreceptors in hypothalamus= Release of ADH from posterior pituitary- Renal water retention * Stimulation of thirst centre in hypothalamus- Increased water intake * Movement of water from ICF to ECF

Answer 234

ADH, Aldosterone, atrial natriuretic peptide

Answer 235

net movement of solvent molecules through a semipermeable membrane to a higher solute concentration (i.e. lower water conc.)

Answer 236

measure of the number of dissolved particles per kg of fluid

Answer 237

measure of the number of dissolved particles per L of fluid

Answer 238

pressure applied to a solution, by a pure solvent, required to prevent inward osmosis, through a semipermeable membrane

Answer 239

form of osmotic pressure exerted by protein that tends to pull fluid into its solution - water moves from interstitial fluid into plasma

Answer 240

Pressure difference between capillary blood(plasma) and interstitial fluid - water and solutes move from plasma into interstitial fluid

Answer 241

Acts to increase water reabsorbtion in collecting ducts of the kideny in order to dilute the solute and return water in ECF to normal

Answer 242

Decrease in water in ECF= decrease in effective circulating volume= decrease in renal blood flow Results in release of renin from the juxtaglomerular kidney cells in the kidneys Renin converts angiotensinogen to angiotensin 1, Angiotensin converting enzyme (ACE) then converts angiotensin 1 into 2 which in turn triggers the release of aldosterone from the adrenal cortex above the kidneys Angiotensin 2 and aldosterone increase na + reabsorption in the kidenys in exchange for potassium or hydrogen secretion Also stimulate ADH release Sodium reabsorption brings water with it to return water in ECF to normal Osmolality (sodium) is controlled by changing water, Water is controlled by changing osmolality (sodium)

Answer 243

water deprivation, vomiting, diarrhoea, burns, heavy sweating, diabetes insipidus (literally pee bucket loads since too little ADH produced), diabetes mellitus & drugs

Answer 244

thirst, dry mouth, inelastic skin, sunken eyes, raised haematocrit (viscosity of blood), weight loss, confusion & hypotension

Answer 245

High intake/ decreased loss of water, excess ADH

Answer 246

Hyponatraemia (low sodium levels), cerebral over- perfusion (due to high blood volume and thus pressure) - causes headaches, confusion & convulsions

Answer 247

Excess water in a body cavity

Answer 248

Excess water in the Intracellular tissue space or distruption of the filtration and osmotic forces of circulation fluids * Inflammatory (leakage)=proteins leak out due to increased vascular permeability - they bring in water, thereby diluting the toxins - fibrinogen polymerises to form a fibrin mesh and immunoglobulins collect * Venous (increased end pressure)- due to increased venous pressure or venous obstruction from a thrombus * Lymphatic (blocked)- Obstructions from a tumour/parasite * Hypolabuminaemic- Lower oncotic pressure

Answer 249

Fluid pushed through the capillary due to high pressure within the capillary Low protein content

Answer 250

Fluid that leaks around the cells of the capillaries caused by inflammation &↑permeability of pleural capillaries to proteins. High protein content

Answer 251

ECF volume expansion (Heart, Kidney failure, Cirrhosis with ascites) Loss of Intravascular fluid into interstitial space Low effective circulating volume stimulates RAAS and ADH Renal sodium retention, plus water retention Oedema

Answer 252

10ml of fluid- Normal pleural space Balance between hydrostatic and oncotic forces in the visceral and parietal pleural vessels and lymphatic drainage PLEURAL EFFUSIONS= result from disruption of this balance Diff. fluids can enter the pleural cavity. Transudate, exudate Pleural fluid protein is measured to differentiate between Transudate (Cirrhosis, Hypoalbimunaemia, Peritoneal dialysis) and Exudate (High protein levels compared to transudates, Malignancy, Pneumonia) May also contain cells, bacteria and enzymes)

Answer 253

High sodium. Causes: renal failure, mineralocorticoid excess (sodium excess), osmotic diuresis (increased urine rate due to high amount of water) and diabetes insipidus. Consequences: cerebral intracellular dehydration - high sodium = low H2O which then dehydrates the brain as there is a lower water concentration since H2O leaves intracellular to go extracellular as solute concentration increases - osmosis

Answer 254

Low sodium. Causes: diuresis (increase urine rate), Addison’s disease, excess IV fluids & oedema. Consequences: Intracellular over hydration - hypotension since H2O goes intracellular as solute concentration increases - osmosis

Answer 255

Excretion from kidneys is controlled by aldosterone as it controls the Na/K pump

Answer 256

High potassium. Causes: renal failure, diuretics/ACE inhibitors, Addison’s, Acidosis. Consequences: Risk of myocardial infarction since high potassium levels mess with resting potential generated in heart for heart contraction

Answer 257

Low potassium. Causes: diarrhoea, vomiting, alkalosis, hypomagnesaemia (low magnesium levels). Consequences: weakness & cardiac dysrhythmia (abnormal heart beat - again since K is necessary for resting potentials and thus action potential generation etc.)

Answer 258

High calcium. Causes: primary hyperparathyroidism (parathyroid gland producing too much parathyroid hormone meaning calcium is leached from bone to increase blood calcium levels), skeletal metastases, vitamin D toxicity and tuberculosis. Consequences: metastatic calcification (deposition of calcium salts in otherwise normal tissues - resulting in stones) and kidney stones (renal calculi)

Answer 259

Low calcium Causes: Vitamin D deficiency, magnesium deficiency, renal disease, parathyroidectomy (no parathyroid hormone released) & intestinal malabsorption. Consequences: tetany (spasms of the hands, feet & voice box)

Answer 260

Lipid, protein and carbohydrate that exist in a fluid state

Answer 261

Contains Glycolipids: communication, joins cells to form tissues and stability Glycoproteins: for cell to cell recognition and acts as receptors Cholesterol: maintains fluidity in membrane

Answer 262

Amphipathic- both hydrophilic and phobic

Answer 263

Acts as selective barrier to the outside environment and compartmentalise cells Cell membrane is semipermeable; absorbs nutrients and expels waste and maintains intracellular balance Helps cells respond to signals via receptors Has molecules on it for inter cellular adhesion Can act as an insulator i.e. myelin sheath

Answer 264

Occluding: tight junctions help seal cells together in an epithelial sheet to prevent leakage of molecules between them Anchoring: * ACTIN filaments; enable cell to cell adhesion through adherens junctions (ADHERENS JUNCTION JOINS ACTIN BUNDLE IN ONE CELL TO A SIMILAR BUNDLE IN ANOTHER CELL - HELPS KEEP CELLS TOGETHER) & cell to matrix (external to cell) adhesion through adherens junctions too. * INTERMEDIATE FILAMENTS; enable cell to cell adhesion through desmosomes (cell surface adhesion proteins + intracellular keratin cytoskeletal filaments - they resist shearing forces & JOIN THE INTERMEDIATE FILAMENTS IN ONE CELL TO THOSE IN A NEIGHBOUR) & cell to matrix adhesion through focal adheren junctions. HEMIDESMOSOMES; anchor intermediate filaments in a cell to the basal lamina Communicating: gap junctions- allows the passage of small water soluble ions and molecules

Answer 265

Energetic process to absorb/engulf molecules into a cell. Some extracellular fluid is usually engulfed too along with the molecule etc. - a portion of the membrane is invaginated to form a membrane bound vesicle called an endosome Receptor mediated - specific, found in depressed areas (coated pits) - allows the cell to get the molecules it needs. Ligands bind to receptor, this complex is engulfed - releasing the ligand into the cytosol (fluid portion of the cytoplasm outside the cell organelles) Pinocytosis (drinking) - bringing in dissolved solutes

Answer 266

Occurs in neutrophils & macrophages - they implement phagocytosis (eating) whereby they engulf entire cells/macromolecules to form a phagosome

Answer 267

Vesicle from the golgi apparatus, fuse with the plasma cell membrane, resulting in the expulsion of waste or the secretion of enzyme/hormones

Answer 268

Facilitated diffusion Passive diffusion Active transport

Answer 269

the movement of solutes from a region of their high concentration to a region of their low concentration through protein channels (WITHOUT CARRIER PROTEINS). This continues until dynamic equilibrium is reached. e.g. Glucose - protein assisted which is regulated by insulin. Voltage gate channels activated by action potentials

Answer 270

Passive diffusion e.g. gaseous exchange along chemical gradient

Answer 271

The movement of solutes from a region of low concentration to a region of high concentration against the concentration gradient. Both transmembrane carrier protein and ATP is required. e.g Na/K ATPase pump - going against chemical and electrical gradients

Answer 272

Gateway to intracellular signals: Examples; open a channel, activate a intracellular enzyme, induce second messenger (peptide hormone binds to receptor) & migrate nucleus to receptor-ligand complex Examples: enzyme linked receptor e.g. tyrosine kinase - transfers a phosphate group from ATP to a protein in a cell thus acts like an on/off switch, ion channel linked receptor - participate in rapid signalling events found in electrically active cells like neurons, also referred to as ligand gated ion channels, G-protein coupled receptors - sense molecules outside the cell and activate inside signal transduction pathways to ultimately illicit a cellular response

Answer 273

Carbohydrates (4kcal/g) Protein (4kcal/g) Alcohol (7kcal/g) Lipid (9kcal/g - gives the most energy per gram)

Answer 274

Amino acids in chains, contain carbon, hydrogen, oxygen & nitrogen (maintains nitrogen balance- when starving/dieting, there is a decrease in proteins thus decrease in nitrogen and that affects cell functions

Answer 275

3 fatty acids esterified to one glycerol mostly - most efficient energy source

Answer 276

typically ethanol, highly energetic

Answer 277

chemical reactions that occur in a living organism

Answer 278

amount of energy needed to keep the body alive in the rest state. It is the energy needed to keep the heart pumping, the brain working and the liver and kidneys functioning - BMR = 1kcal/kg body mass/hr (24kcal/kg/day), an adult requires approximately 0.8g/kg ideal body weight protein per day

Answer 279

High BMI Hyperthyroidism Low ambient temperature Fever/infection Pregnancy (due to increase in weight and thyroid hormone) Exercise

Answer 280

Age (as you get older, BMR decreases) Gender (female have lower BMR since they have less metabolically active tissues) Starvation Hypothyroidism (less thyroid hormone = lower BMR)

Answer 281

Energy to support our BMR and our physical | activity + energy required to process food we eat (diet induced thermogenesis)

Answer 282

Stored as triglycerides (excess lipid) (approx 15kg) Stored as glycogen (excess glucose) (approx 200g in liver & 150g in muscle) Stored as protein (approx 6kg) Carbohydrates account for 30% of ATP production at rest Lipids account for 70% of ATP production at rest Proteins are often used in longer periods of starvation

Answer 283

Energy utilisation | biosynthesis or macromolecules, muscle contraction, active ion transport and thermogenesis

Answer 284

Respiration (energy production from carbs, lipids and proteins, 02 in C02 out= ATP

Answer 285

Three main parts; Adenine- Base found in nucleotides in DNA/RNA also a component part in NAD/ FAD. adenine forms adenosine when attached to ribose Ribose- Simple 5C sugar (monosaccharide) also found in RNA, forms adenosine (nuceloSide) with adenine Phosphate- Three phosphate groups (hence triphosphate)

Answer 286

Two phosphoanhydride bonds, when first hydrolysed it produced ADP and when the second is hydrolysed it produces AMP High energy bonds

Answer 287

When the phosphate bonds are broken energy is released BUT to ‘break’ bonds an input of energy is required. As bonds reform in the products of the reaction of the hydrolysis of ATP energy is released. The energy released making the new bonds is greater than the energy required to hydrolyse the bonds (since they are relatively weak) thus meaning the hydrolysis of ATP gives out energy

Answer 288

Glycolysis Kreb’s cycle Oxidative phosphorylation Substrate level phosphorylation Electron transport chain Beta oxidation

Answer 289

In the Cytosol

Answer 290

1 glucose + 2ADP + 2 NAD+ > 2 x pyruvate + 4 x ATP + 2NADH + 2H+ + 2H20 SIMPLIFIED: Glucose + 2ADP + 2Pi + 2NAD+ > 2 Pyruvate + 2ATP + 2NADH + 2H+ + 2H20

Answer 291

enzyme that adds/removes phosphate group to things from an ATP

Answer 292

enzyme that rearranges structure of substrate without changing the molecular formula. (Similar to a mutase)

Answer 293

enzyme that creates or breaks carbon-carbon bonds

Answer 294

enzyme that moves hydride ion (H-) to an electron acceptor e.g. (NAD+ of FAD+)

Answer 295

enzyme that produces a carbon=carbon double bond by removing a hydroxyl group (OH)

Answer 296

From the diagram above; the NAD+ and H+ released in step 6 of glycolysis, is used in the conversion of pyruvate to lactate which releases NAD+ which can once again be used in step 6. Pyruvate > Lactate: In anaerobic conditions, the pyruvate produced cannot enter the Kreb’s cycle or undergo Oxidative Phosphorylation since these processes require oxygen, instead, the pyruvate can be converted to lactate: Glucose + 2 ADP + 2 Pi > 2 Lactate + 2 ATP + 2 H2O Fate of lactate: some of the lactate that is formed is released into the blood and taken up by the heart & brain where it is converted back to pyruvate and used as an energy source. Another portion is taken up by the liver where it is used as a precursor for the formation of glucose, which is then released into the blood where it becomes available as an energy source for cells.

Answer 297

Yes For example, in erythrocytes (e.g. red blood cells), they contain the enzymes for glycolysis but do not have mitochondria (thus cannot use the Kreb’s cycle or oxidative phosphorylation). All their ATP production therefore occurs by anaerobic glycolysis. Also in some skeletal muscles there are considerable amounts of glycolytic enzymes but few mitochondria - thus a lot of ATP production is done by glycolysis. Despite this the majority of cells do not have sufficient amounts of glycolytic enzymes or enough glucose to provide for glycolysis to meet the energy requirement of the cell using glycolysis alone

Answer 298

PHOSPHOFRUCTOKINASE-1 (PFK-1) IS PH DEPENDENT AND IS | INHIBITED BY ACIDIC CONDITIONS

Answer 299

AMP (adenosine monophosphate)- allosteric activator (modifies the AS of the enzyme so that the affinity for the substrate increases) of Phosphofruktokinase-1 (PFK-1). AMP binds to PFK-1 resulting in a conformational change increasing affinity for fructose-6- phosphate ``` Adenosine triphosphate (ATP) is an allosteric inhibitor (modifies the active site of the enzyme so that the affinity for the substrate decreases) for PFK-1 ``` Thus at low ATP levels = fast reaction speed of PFK-1 > fructose 1,6 bisphosphate, and at high ATP levels = slow reaction speed of PFK-1 > fructose 1,6 bisphosphate AMP opposes the allosteric inhibition of ATP

Answer 300

Mitochondrial matrix

Answer 301

Acetyl CoA + 3NAD+ + FAD + GDP + ADP + Pi + 2H2O > 2CO2 + CoA + 3 NADH + 3H+ + FADH2 + GTP + ATP

Answer 302

Acetyl coenzyme A. it is derived from the B vitamin pantothenic acid and functions primarily to transfer acetyl groups (2C) from one molecule to another

Answer 303

From pyruvate or beta oxidation of fatty acids or from amino acid breakdown

Answer 304

Since oxidative phosphorylation is required to covert NADH & FADH2 back to NAD+ and FAD to be used in the conversion of Isocitrate to a-Ketoglutarate and a-Ketoglutarate to Succinyl coenzyme A & Succinate to Fumarate & Malate to Oxaloacetate.

Answer 305

Can I Keep Selling Socks For Money, Officer? Citrate, Isocitrate, a-Ketoglutarate, Succinyl CoA, Succinate, Fumarate, Malate, Oxoloacetate

Answer 306

Fatty acid is oxidised Aerobic only Dependent on oxygen Good blood supply Adequate numbers of mitochondria

Answer 307

FA is just a carboxylic acid group with lots of carbons attached FA must be activated in the cytoplasm before being oxidised in the mitochondria Process: FA + ATP + CoA= Acycl CoA + PPI (pyrophosphate) + AMP. Adenosine is taken from ATP and used to make Acyl Coenzyme A Occurs in the mitochondria (but most FA (>12C long)cant get through outer mitochondrial membrane on their own

Answer 308

Acyl CoA --> Enzyme Carnitine acyltransferase 1 (resides in the outer mitochondrial membrane) --> Acyl Carnitine Coenzyme is is remove for Acyl CoA and recycled. the molecule Carnitine is added, so can be transported into the mitochondria through the outer mitochondrial membrane. Once inside the mitochondria another enzyme Carnitine acyltransferase 2 converts Acyl Carnitine back to Acyl CoA Coenzyme A is re-added and the carnitine is ripped off to regenerate Acyl CoA. the carnitine can then diffuse through the outer mitochondrial membrane to be used again to covery Acyl CoA to Acyl Carnitine

Answer 309

Fatty Acid oxidation yields more energy per carbon than the oxidation of carbohydrate. The net result of the oxidation of one mole of oleic acid (an 18C FA) will be 146 moles of ATP compared to 38 moles of ATP produced from 1 mole of glucose

Answer 310

They can't get through the blood-brain barrier

Answer 311

1 MOL: NADH FADH2 Acetyl CoA

Answer 312

Oxidative phosphorylation

Answer 313

When hormones signal fasting or increased deman

Answer 314

Linoleic acid (18C), Oleic acid (18C), Palmitic acid (16C) Arachidonic acid (20C)

Answer 315

Inner mitochondria membrane

Answer 316

Cytochromes (contain iron and copper co-factors, structure resembles the red iron- containing haemoglobin) Associated proteins embedded in the inner mitochondrial membrane surface

Answer 317

2 electrons from 1 Hydrogen atom are initially transferred either from NADH + H+ or FADH2 to one of the protein in the ETC These electrons are then successively transferred to other compounds in the chain redox reactions, until the electrons are finally transferred to molecular oxygen, which then combines with hydrogen ions (protons) to form water

Answer 318

free hydrogen ions and the hydrogen-bearing coenzymes (NADH and FADH2), that had been released earlier in the electron transport chain when the electrons from the hydrogen atoms were transferred to the cytochromes.

Answer 319

Coenzyme hydrogens transferred to water

Answer 320

Pump cytochromes to pump hydrogen ions from the matrix into the intermembranal space Creates another source of potential energy in the form of Hydrogen/ion conc. grad. across the membrane Embedded in the inner mitochondrial membrane are enzymes called ATP synthase. This enzyme forms a channel in the membrane allowing H ions to flow back into the matric via chemiosmosis- moving from an area of high conc. of H ions to an area of low conc. During this process, the energy of the concentration gradient is converted into chemical bond energy by ATP synthase, which then catalyses the formation of ATP from ADP and Pi. The transfer of electrons to oxygen produces on average around 2.5 and 1.5 molecules of ATP for each molecule of NADH + H+ & FADH2 respectively.

Answer 321

C6H12O6 + 6O2 + 38 ADP + 38 Pi --> 6CO2 + 6H20 + 34-38 ATP (There is debate to how much ATP is produced from glycolysis, Kreb's cycle and Oxidative phosphorylation but its roughly between 34-38 ATP molecules (38 is theoretical and assumes all NADH produced in glycolysis and Kreb's enter oxidative phosphorylation and all the free H ions are used in the chemiosmosis for ATP)

Answer 322

During high rates of fatty acids oxidation, primarily in the liver (hepatocytes), large amounts of acetyl-CoA are generated. These exceed the capacity of the Kreb’s/TCA cycle, and one result is the synthesis of ketone bodies.

Answer 323

Ketone bodies (acetone, acetoacetate & B-hydroxybutyrate) are synthesised in the mitochondrial matrix from Acetyl CoA generated from b-oxidation

Answer 324

When carbohydrate utilisation is low or deficient, the level of oxaloacetate will also be low resulting in a reduced flux through the Kreb’s cycle - leading to an increased release of ketone bodies from the liver to be used as fuel by other tissues

Answer 325

When the glycogen in the liver is high the production of b-hydroxybutyrate increases. Another fate of the acetoacetate is that it can spontaneously be converted to acetone. Since acetone is volatile it is rapidly expired by the lungs

Answer 326

Cells transport the acetoacetate and b-hydroxybutyrate from the blood into the cytosol then into the mitochondrial matrix. Here b-hydroxybutyrate is oxidised back to acetoacetate. Acetoacetate can then be activated to Acetoacetyl CoA which can then be cleaved into two molecules of Acetyl CoA by the thiolase enzyme (same enzyme involved in b-oxidation). Then the Acetyl CoA can be used in the Kreb’s cycle to produce ATP

Answer 327

THUS CANNOT UTILISE KETONE BODIES AS FUEL since they cannot be converted to Acetyl CoA in the liver - this ensure that extrahepatic tissues have access to ketone bodies as a fuel source during prolonged starvation

Answer 328

The last remnants of fat are oxidised, the heart and skeletal muscle will consume primarily ketone bodies in order to PRESERVE GLUCOSE FOR USE BY THE BRAIN - when glucose in the brain decreases then the brain CAN use ketone bodies for energy

Answer 329

Level of ketogenesis in the liver

Answer 330

Production of ketone bodies occurs at a relatively slow rate during normal feeding and under normal physiological status Normal physiological responses to carbohydrate shortages cause the liver to increase production of ketone bodies from the acetyl-CoA generated from fatty acid oxidation. This allows the heart and skeletal muscles primarily to use ketone bodies for energy, thereby preserving the limited glucose for use by the brain. The most significant disruption in the level of ketosis occurs in untreated insulin- dependent diabetes mellitus

Answer 331

Results from reduced supply of glucose (since there will be a significant decline in circulating insulin) and an increase in fatty acid oxidation (due to an increase in circulating glucagon). The increased production of Acetyl-CoA leads to ketone body production that exceeds the ability of peripheral tissues to oxidise them. Ketone bodies are relatively strong acids (pH 3.5), and their increase lowers the pH of blood. This acidification of the blood can have many consequences but most critical is the fact that it IMPAIRS THE ABILITY OF HAEMOGLOBIN TO BIND TO OXYGEN - note if a patient is in diabetic ketoacidosis, the excess ketones in the blood will result in their BREATH SMELLING OF PEAR DROPS (KETONES).

Answer 332

Oxygen: favours reduction in single electron steps, two unpaired electrons, parallel spin, permits combustion, cellular respiration (electron transport chain), formation of free radicals & is highly reactive

Answer 333

highly reactive oxygen containing compounds that are free radicals (have a single unpaired electron in their orbital) or compounds that are readily converted to oxygen free radicals in the cell - these compounds contribute to ageing, homeostasis and some cancers.

Answer 334

highly reactive oxygen containing compounds that are free radicals (have a single unpaired electron in their orbital) or compounds that are readily converted to oxygen free radicals in the cell - these compounds contribute to ageing, homeostasis and some cancers. Reactive free radical extract electrons (usually as hydrogen atoms) from other compounds to complete their own orbitals, thereby initiating free radical chain reactions. - The hydroxyl radical is probably the most potent of the ROS

Answer 335

UV radiation, tobacco and drugs

Answer 336

NADPH & the electron transport chain

Answer 337

Formation occurs through the reduction of oxygen in 4 steps: - Firstly oxygen is reduced by a single electron to form superoxide (O2•–) [free radical] Then the superoxide is reduced further to form hydrogen peroxide (H2O2) [not a free radical] H2O2 is reduced further to produce hydroxyl radical (OH•) [free radical] Then lastly its further reduced to water (H2O)

Answer 338

Not a radical, but it is a ROS since it is readily converted to the hydroxyl radical (OH•) in cells. Its also lipid soluble so can cause damage away from site of formation. Transition metals such as Fe2+ or Cu2+, catalyse the formation of the hydroxyl radical from hydrogen peroxide in the nonenzymatic Fenton reaction (the iron dependent generation of a hydroxyl radical from hydrogen peroxide) by donating a single electron

Answer 339

H2O2 + Fe2+ > Fe3+ + OH- + OH•

Answer 340

O2•– + H2O2 + H+ > O2 + H2O + OH• - The hydroxyl radical can also be formed by the Haber-Weiss reaction involving superoxide (O2•–) Combines with the Fenton reaction to form the Haber- Weiss cycle (4 Reactions to produce an OH• and consume H202

Answer 341

Fe2+ + H2O2 > Fe3+ + OH- + OH• [Fenton reaction] OH• + H2O2 > H2O + O2•– + H+ O2•– + H+ + H2O2 > O2 + OH• + H2O [Haber-weiss reaction] Fe2+ + OH• + H+ > Fe3+ + H2O

Answer 342

Most potent of ROS Radical characteristics- lipid soluble (thus can cause superoxide damage away from site of hydrogen O2·- Produced by electron transport chain. Generates other radicals locally formation as well as damaging peroxide H2O2 Generates radicals with transition metals. Lipid soluble lipid bilayers) Hydroxyl OH· Most reactive radical Initiator of chain reactions that form lipid peroxides and organic radicals

Answer 343

Proteins, lipids, carbohydrates and nucleic acid Damage membranes of: cells, nucleus, mitochondria and endoplasmic reticulum Cell membrane damage results in the increased permeability of the membrane resulting in an influx of calcium, water and sodium Diseases: Emphysema, Parkinson's, Acute renal failure and Diabetes DNA can also be damaged by hydroxyl radial- results in strand breaks and base alterations- Mutations

Answer 344

Immune system defence against bacteria Sudden release of ROS by immune cells (Neutrophils, macrophages and monocytes) during phagocytosis Immune cells utilise NADPH oxidase to reduce oxygen to superoxide Superoxide is released (which is then reduced to hydrogen peroxide, which in turn can be reduced to hydroxyl radical etc.), which then generates other reactive oxygen species Neutrophils & monocytes use myeloperoxidase to further combine H2O2 with Cl- to produce hypochlorite (which plays a role in destroying bacteria by damaging bacterial cell membranes) (ClO-) [H2O2 + Cl- > H2O + NADP+ O2- Cl-]

Answer 345

Prevents the formation of ROS Causes chronic granulomatous disease (X-linked) (build up of pathogens in phagocytes since they can engulf but NOT kill them - leads to severe skin infections with bacteria or fungi)

Answer 346

Antioxidant enzymes: Antioxidant vitamins: Vitamin E - found in liver, free radical scavenger, protects against lipid peroxidation and terminates free radical propagation in membranes, Vitamin C - e.g ascorbic acid, reacts with superoxide & hydroxyl radical and regenerates reduced vitamin E Cellular compartmentalisation: Respiratory burst taking place in phagosomes so harmful chemicals don't get out and damage healthy tissue

Answer 347

Superoxide dismutase - converts superoxide to hydrogen peroxide (non toxic unless converted to another ROS) & oxygen Catalase - catalyses conversion of hydrogen peroxide to water & oxygen and protects white blood cells against own respiratory burst Glutathione Peroxidase - catalyses the reduction of hydrogen peroxide to water and a disulphide (GSSG)

Answer 348

Proton/H+ donor | HA (acid) H+ + A- (conjugate base)

Answer 349

Proton/H+ acceptor: | B (base) + H+ BH+ (conjugate acid)

Answer 350

A compound that ionises completely in solution to form hydrogen ions and a base

Answer 351

Compounds that are only partially ionised in solution

Answer 352

ALL ARE WEAK ACIDS OR BASES WITH THE CONJUGATE BASE OR ACID RESPECTIVELY. Solution which resists changes in pH when small quantities of strong acids or base are added. It limits the change in hydrogen ion concentration (and thus pH) when hydrogen ions are added or removed from the solution. When hydrogens are in excess the extra ions are taken up and when hydrogens are in short supply more hydrogen ions are released.

Answer 353

pH = pKa + log([HCO3 -] / [CO2])

Answer 354

The process of metabolism generates hydrogen ions. Small amounts are from the oxidation of amino acids and the anaerobic metabolism of glucose to lactic and pyretic acid Far more hydrogen ions and thus acid are produced as a result of carbon dioxide (CO2) release from oxidative (aerobic) metabolism. Although CO2 doesn't contain hydrogen ions it rapidly reacts with water to form carbonic acid (H2CO3), which further dissociates into hydrogen & bicarbonate ions (HCO3 -): This reaction occurs throughout the body and in certain circumstances is speeded up by the enzyme carbonic anhydrase. Carbonic acid is a weak acid and with bicarbonate (its conjugate base) forms the MOST IMPORTANT BUFFERING SYSTEM IN THE BODY

Answer 355

* Blood & tissue buffering * Excretion of CO2 by the lungs * Renal excretion of H+ and regeneration of HCO3 - Buffers are able to limit changes in hydrogen ion concentrations - this prevents the large quantities of hydrogen ions produced by metabolism resulting in dangerous changes in blood or tissue pH

Answer 356

Bicarbonate Proteins Haemoglobin

Answer 357

this is the most important buffer system in the whole body (equation above). Despite the fact that bicarbonate is not an efficient buffer, its efficiency is improved because CO2 is removed at the lungs & bicarbonate is regenerated by the kidneys.

Answer 358

Many proteins, notably albumin, contain weak acidic and basic groups within their structure. Thus, plasma and other proteins form important buffering systems. Intracellular proteins limit pH changes within cells, whilst the protein matrix of bone can buffer large amounts of H+ ion in patients with chronic acidosis

Answer 359

Its not only important in the carriage of oxygen to the tissues but also in the transport of CO2 and in buffering hydrogen ions. Haemoglobin binds both CO2 & H+ and is thus a powerful buffer. Deoxygenated haemoglobin has the strongest affinity for both CO2 & H+; thus its buffering effect is strongest in the tissues.

Answer 360

Little CO2 is produced in red cells thus CO2 produced by tissues passes easily into the cell down a concentration gradient. CO2 then either combines directly with haemoglobin or combines with water to form carbonic acid. The CO2 that binds directly with haemoglobin combines reversibly with terminal amine groups on the haemoglobin molecule to form carbaminoheamoglobin . In the lungs the CO2 is released and passes down the concentration gradient in to the alveoli - THIS IS THE BUFFERING OF CO2

Answer 361

In tissues, dissolved CO2 passes into the red blood cells down the concentration gradient where it combines with water to form carbonic acid. This reaction is catalysed by the enzyme carbonic anhydrase. Carbonic acid then dissociates into bicarbonate and H+ ions. The H+ ions bind to reduced haemoglobin to form HHb. BICARBONATE IONS (HCO3 -) GENERATED BY THIS PROCESS PASS BACK INTO THE PLASMA IN EXCHANGE FOR CHLORIDE IONS (CL-) - this ensures that there is no net loss or gain of negative ion in the red blood cell. In the lungs this process is reversed and H+ ions bound to haemoglobin recombine with bicarbonate to form CO2 which passes into the alveoli. In addition, reduced Hb (haemoglobin) is reformed to return to the tissues.

Answer 362

CO2 is responsible of the majority of H+ ions produced by metabolism. Thus, the RESPIRATORY SYSTEM forms the single most important organ involved in the control of hydrogen ions. In the lungs, the arterial partial pressure of CO2 (PaCO2) is INVERSELY PROPORTIONAL to alveolar ventilation - i.e. if alveolar ventilation falls the PaCO2 rises. Thus, relatively small changes in ventilation can have a profound effect on hydrogen ion concentration and thus pH. Ideal pH = 7.4: • pH > 7.45 - ALKALOSIS • pH < 7.35 - ACIDOSIS Alkalosis and acidosis can be respiratory or metabolic

Answer 363

Disturbances of the body’s acid base balance results in the plasma contains either too many hydrogen ion (acidaemia - condition related to this is acidosis) or too few hydrogen ions (alkalaemia - condition related to this is alkalosis). The the pH is too low in acidaemia (less than 7.35) whilst in alkalaemia the pH is too high (greater that 7.45) - these disturbances may be due to respiratory causes (i.e. changes in PaCO2) or non-respiratory (METABOLIC) causes.

Answer 364

Results when the PaCO2 is above the upper limit of normal (>6kPa). Respiratory acidosis is most commonly due to decreased alveolar ventilation causing decreased excretion of CO2. Less commonly, it is due to excessive production of CO2 by aerobic metabolism - this may occur in syndromes such as malignant hyperpyrexia (fever with an extreme elevation of body temperature)

Answer 365

Results from the excessive excretion of CO2, and occurs when the PaCO2 is less than 4.5kPa - this is commonly seen in hyperventilation due to anxiety In more serious diseases, such as severe asthma or moderate pulmonary embolism, respiratory alkalosis may occur In both respiratory acidosis & alkalosis the compensation time is VERY QUICK, MEANING THERE CAN BE A RAPID RESPONSE TO COUNTER THE ACIDOSIS/ ALKALOSIS THUS IT HAS A LIMITED EFFECT

Answer 366

May result from either an excess of acid due to increased production of organic acids or reduced buffering capacity due to low concentration of bicarbonate Excess H+ production is the most commonest cause of metabolic acidosis and results form the the excessive production of organic acids (usually lactic or pyretic acid) as a result of anaerobic metabolism. This may result from local or global tissue hypoxia (deficiency in the amount of oxygen reaching the tissues).

Answer 367

Reduced arterial oxygen content: for example because of anaemia or reduced PaCO2 Hypoperfusion (low perfusion) - for example, any cause of reduced cardiac output may result in metabolic acidosis (e.g hypovolaemia (low blood volume), cardiogenic shock etc.). Also local hypoperfusion in conditions like ischaemic bower or ischaemic limb may cause acidosis Reduced ability to use oxygen as a substrate - e.g. in conditions like severe sepsis and cyanide poisoning anaerobic metabolism occurs as a result of mitochondrial dysfunction

Answer 368

Cells are unable to use glucose to produce energy due to the lack of insulin. Fats form a major energy source and result in the production of ketone bodes (acetoacetate and 3- hydroxybutyrate) from acetyl coenzyme A. Hydrogen ions are released during the production of ketones resulting in metabolic acidosis

Answer 369

This results from renal tubular dysfunction and usually occurs in conjunction with inadequate reabsorption of bicarbonate. Any form of renal failure may result in metabolic acidosis.

Answer 370

Aldosterone regulates sodium reabsorption in the distal renal tubule. As sodium reabsorption and H+ excretion are linked, a lack of aldosterone (e.g in Addison’s disease) tends to result in reduced sodium reabsorption and thus a reduced ability to excrete H+ into the tubule resulting in reduced H+ loss.

Answer 371

Intestinal secretions are high in sodium bicarbonate. The loss of small bowel contents or excessive diarrhoea results in the loss of large amounts of bicarbonate resulting in metabolic acidosis - this can occur in Cholera or Crohn’s disease.

Answer 372

May result from the excessive loss of H+ ions, the excessive reabsorption of bicarbonate or the ingestion of alkalis Excess H+ loss - since gastric secretions contain large quantities of hydrogen ions, the loss of gastric secretions will result in metabolic alkalosis - this occurs in prolonged vomiting or pyloric stenosis Excessive reabsorption of bicarbonates - since bicarbonate and chloride concentrations are linked, if chloride concentration falls or chloride losses are excessive the bicarbonate will be reabsorbed to maintain electrical neutrality. Chloride can be lost from the gastro-intestinal tract, thus in prolonged vomiting it is not only the loss of hydrogen ions that results in alkalosis but also the chloride losses which in turn results in bicarbonate reabsorption. Chloride losses may also occur in the kidneys as a result of diuretic drugs - the thiazide and loop diuretic are a common cause of metabolic alkalosis. These drugs cause increased loss of chloride in the urine resulting in excessive bicarbonate reabsorption In both metabolic acidosis & alkalosis COMPENSATION CAN TAKE TIME TO COME INTO AFFECT RESULTING IN A DELAYED RESPONSE MEANING THAT THE ACIDOSIS OR ALKALOSIS HAS A GREATER EFFECT THAN IF IT WAS RESPIRATORY

Answer 373

The difference in serum concentration of cations (positive) and anions (negative) e.g. Cl-, HCO3 -, Na+, K+ - Equation: (Na+ + K+) - (HCO3- + Cl-) Not all ions are included e.g. K+, PO4 -, SO4 - Normal value is between 3-11mEq/mol Can be used to help diagnose cause of metabolic acidosis - if there is a high anion gap or normal anion gap - can be used to see if cause is excessive loss of bicarbonate or excess H+ production etc.

Answer 374

Lungs/respiratory: Alkalosis: hyperventilate and blow off CO2 Acidosis: slow down, retain CO2 Rapid response, limited effect Kidneys/metabolic: Alkalosis: excrete H+, retain HCO3- Acidosis: retain H+, Excrete HC03- Delayed response, greater effect

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