describe the general structures and functions of carbohydrates
general formula (CH2O)n
- may contain aldehyde (aldose) or keto groups
- aldehydes and ketones react with an alcohol to form cyclic groups
- monosaccharides are single sugar units with 3-9 carbons
- disaccharides are two sugar units
- oligosaccharies are 3-12 units of sugars
- polysaccharides are 10-1000s of sugar units
name some common sugars and what they are in humans
- glucose = single 6C monosaccharide. Energy source and broken down to pyruvate in glycolysis
- fructose = fruit sugar. monosaccharide
- sucrose = table sugar. Glucose-Fructose disaccharide.
- lactose = milk sugar. Glucose-Galactose disaccharide.
- maltose = glucose-glucose disaccharide. Often found in processed food
- starch = polymer of β glucose. Carbohydrate storage molecule in plants
- glycogen = polymer of glucose. Carbohydrate storage molecule in animals. Highly branched
therefore the 3 main dietary monosaccharides are glucose, fructose and galactose
name some common sugars and what they are in humans
- glucose = single 6C monosaccharide. Energy source and broken down to pyruvate in glycolysis
- fructose = fruit sugar. monosaccharide
- sucrose = table sugar. Glucose-Fructose disaccharide.
- lactose = milk sugar. Glucose-Galactose disaccharide.
- maltose = glucose-glucose disaccharide. Often found in processed food
- starch = polymer of β glucose. Carbohydrate storage molecule in plants
- glycogen = polymer of glucose. Carbohydrate storage molecule in animals. Highly branched
therefore the 3 main dietary monosaccharides are glucose, fructose and galactose
how are the main dietary carbohydrates digested
starts extracellularly in the GI tract by glycosidase enzymes:
- in the saliva, amylase breaks down starch and glycogen into dextrins
- pancreatic amylase then breaks down further into monosaccharides
- any remaining disaccharides are broken down by disaccharidases (attached to the brush border membrane of epithelial cells)
lactase (lactose)
sucrase (sucrose)
pancreatic amylase (α 1-4 bonds)
isomaltase (α 1-6 bonds)
dextrins = small ogliosaccharides
how are monosaccharides, such as glucose, absorbed in the body
- the Na+/K+ pump uses ATP to pump 3Na+ from intestinal epithelial cell into the capillary, at the same time as pumping 2K+ out of capillary into intestinal epithelial cell
- this maintains the Na+ gradient, creating a lower concentration of Na+ inside the intestinal epithelial cells
- this allows the SGLT1 to bring in 2Na+ from the ileum lumen (down CG), bringing with one monosaccharide (against CG) from ileum lumen into the intestinal epithelial cell
- glucose can then (facilitated) diffuse out of intestinal epithelial cell into the capillary via GLUT2 (passive transport down concentration gradient)
- transport, via blood supply, to target tissues
- glucose uptake into target cells via facilitated diffusion using transport proteins (GLUT1-5). Down CG (high→low concentration)
GLUT2 = glucose transporter 2
SGLT1 = sodium-glucose transporter 1
GLUTs have different tissue distribution and affinities, and can be hormonally regulated, ie by insulin
explain why cellulose is not digested in the human GI tract
cellulose has β glycosidic linkages, whereas starch and glycogen hae α glycosidic linkages
- the β bonds in cellulose make it very planar, which are important for its structural function
- the α bonds present in starch/glycogen are much more flexible
- the bonds have different shapes in 3D space, so are cleaved by different enzymes
- humans don’t possess enzyme capable of cleaving β-1,4 glycosidic bonds
what is lactose intolerance
what are the symptoms and mechansim behind symptoms?
difference between primary, secondary and congenital are on different card
where individuals have an inability to digest lactose
lactose is found in dairy products and many processed foods. Caused by different reasons (different card)
- as unable to digest lactose in small intestine, makes it’s way to large intestine
- in large intestine, bacteria start to digest it, and they produce H2 gas and methane etc
- basically a fermentation process
- environment where osmosis pulls water into the large intestine
- this causes dehydration and diarrhoea
other symptoms:
- bloating
- cramps
- flatulence
- vomiting
- rumbling stomach
needs to be treated carefully in infants, as untreated can lead to dangerous dehydration
what is lactose intolerance
what are the symptoms and mechansim behind symptoms?
difference between primary, secondary and congenital are on different card
where individuals have an inability to digest lactose
lactose is found in dairy products and many processed foods. Caused by different reasons (different card)
- as unable to digest lactose in small intestine, makes it’s way to large intestine
- in large intestine, bacteria start to digest it, and they produce H2 gas and methane etc
- basically a fermentation process
- environment where osmosis pulls water into the large intestine
- this causes dehydration and diarrhoea
other symptoms:
- bloating
- cramps
- flatulence
- vomiting
- rumbling stomach
needs to be treated carefully in infants, as untreated can lead to dangerous dehydration
what are the different types of lactose intolerance
primary lactase deficiency
- in most populations, we only express high levels of lactase during infancy
- by age 5-7, lose 90% of our ability to digest lactose
- however, in some populations, particularly NW Europe and USA, where milk is a major dietary component, the ability to digest lactose carries on (LACTOSE PERSISTENT PHENOTYPE)
- in those populations, primary lactose deficiency only refers to individuals who lack this ‘normal’ lactose persistent phenotype
- only occurs in adults
secondary lactase deficiency
- caused by injury to small intestine (gastroenteritis, coeliac, crohn’s, ulcerative colitis etc)
- occurs in both infants and adults
- generally reversible, once epithelial cells recover
congenital lactase deficiency
- extremely rare, autosomal recessive defect in lactase gene
- cannot digest breast milk
- evolution (where babies needed to be able to digest milk) means that this is rare
- give the babies formula instead
describe the glucose-dependency of some tissues
all tissues can remove glucose, galactose and fructise from the blood
- all tissues metabolise glucose
- liver is the major site of fructise and galactose metabolism
- glucose is major sugar in blood, and concentration is relatively constant
- some tissues have an absolute requirement for glucose, and the rate of glucose uptake into these tissues is dependent on its concentration in the blood
- healthy adult on normal diet requires around 180g of glucose per day
- some tissues, such as RBCs, kidney medulla and lens of eye can only use glucose, requiring around 40g
- brain and CNS usually prefer glucose, requiring around 140g per day
- variable amounts are required by tissues for specialised functions (ie synthesis of triacylglycerols in adipose tissue requires glucose metabolism to provide glycerol phosphate)
describe the key features of glycolysis
- central pathway of all carbohydrate (CHO) metabolism
- occurs in all tissues (cytosolic)
- exergonic (energy producing)
- oxidative
- irreversible pathway
- 6C molecules → 2 x 3C molecules (no loss of CO2)
- with one additional enzyme (LDH), it’s the only pathway that can operate anaerobically
what is the purpose of phsophorylation in glycolysis
and enzyme that carries this out
phosphorylation of glucose to glucose-6-phosphate by hexokinase (glucokinase in liver)
- makes glucose negatively charged (anionic)
- prevents passage back across the plasma membrane
- increases the reactivity of glucose to permit subsequent steps
- this idea (initial priming) to get the pathway going is a principle seen in many catabolic pathways
glucose is transported passively into cell by glucose transporters. Glucose could also leave cell pathway. Once its phosphorylated by hexokinase, then glucose is charged and it can no loner go through the glucose transporter ⇢ committed to the cell
what are the main functions of glycolysis
- oxidation of glucose
- NADH production (2 per glucose)
- synthesis of ATP from ADP (net gain is 2 ATP per glucose)
- provides biosynthetic precursors for fatty acids, amino acids and nucleotides
why are there so many steps + enzymes involved in glycolysis?
- chemistry is easier in small stages
- efficient energy conservation
- allows for fine control
- gives versatility:
- allows interconnections with other pathways
- allows production of useful intermediates
- allows part to be used in reverse
describe how some important intermediates are derived from glycolysis
2,3-Bisphosphoglycerate
* produced in red blood cells from 1,3-bisphosphoglycerate (product of phase 2 glycolysis)
* via the bisphosphoglycerate mutase enzyme
* important regulator haemoglobin O2 affinity (promotes release)
glycerol phosphate
- produced in adipose tissues and liver from dihydroxyacetone-P (product of phase 2 glycolysis)
- via the glycerol 3-phosphate dehydrogenase enzyme
- important to triglyceride and phospholipid biosynthesis
- lipid synthesis in adipose tissue requires glycolysis
- however, liver can also phosphorylate glycerol directly
explain how fructose is metabolised
- dietary sucrose is hyrdolysed by the digestive enzyme sucrase → glucose + fructose
- these are absorbed into the bloodstream
- fructose is metabolised largely in the liver
- fructose is phosphorylated by fructokinase so that it is retained in the cell → fructose -1P
- Adolase enzyme catalyses fructose-1P to form glyceraldehyde 3-phosphate which is an intermediate of glycolysis
essential fructosuria + fructose intolerance
what are the clinical links to issues with fructose metabolism
and what enzymes are missing
essential fructosuria
- fructokinase (enzyme that phosphorylates fructose → fructose- 1P)
- fructokinase is missing
- therefore unable to carry out first step of fructose metabolism
- fructose is accumulated and excreted
- fructose in urine, no other clinical signs
- benign condition, just means that there is an energy source that cannot be utilised
fructose intolerance aka hereditary fructose intolerance, HFI
- adolase (enzyme that converts fructose-1P → glyceraldehyde, which is an intermediate of glycolysis)
- adolase missing
- accumulation of fructose-1P substrate in liver
- fructose-1P uses up inorganic phosphates, and therefore inability to have normal ATP control
- leads to liver damage and possible death
- managed by removing fructose and sucrose from diet
explain how galactose is metabolised
dietary lactose is hydrolysed by the digestive enzyme lactase to release galactose and glucose
- these products are absorbed in the bloodstream
- galactose is metabolised largely in the liver
- galactose is phosphorylated by galactokinase → galactose-1P
- galactose-1P is catalysed by uridyl transferase → glucose-1P which goes on to form glucose-6P which is then used in glycolysis
- galactose-1P can also be catalysed by UDP-galactose epimerase → UDP-galactose, which can the form UDP-glucose and then form glycogen
UDP Galactose is used in many metabolic pathways for sythesis of glycoproteins and glycolipids. Production of this is really important for biosynthesis
explain why lactate production is important in anaerobic glycolysis
- total NAD+ and NADH is constant in cell
- therefore glycolysis would stop if all NAD+ is → NADH
- normally, NAD+ is regenerated from NADH in a later stage of metabolism
- in some cells/conditions (ie cells with no stage 3+4 of metabolism or lack of O2), insufficient NAD+ is regenerated
- therefore need to regenerate NAD+ via a different route
- pyruvate → lactate (reduction) by lactate dehydrogenase (LDH)
- reversible enzyme and reaction
- uses NADH and H+ to reduce pyruvate
- regenerates NAD+ for glycolysis to continue
this is important for anaerobic respiration, as glycolysis is the only source of ATP, and therefore the only chance to generate energy for the body
explain how the blood concentration of lactate is controlled
- lactate is transported from anaerobic tissues (with high lactate concentration) to heart, liver and kidney via the bloodstream
in the heart
- due to the high O2 blood supply coming from lungs
- LDH can work in both directions
- lactate can be used to produce pyruvate (oxidation) which can be used to generate energy (+ CO2)
in liver and kidney
- lactate can also be oxidised to form pyruvate by LDH
- pyruvate may be converted to form glucose (gluconeogenesis), which can be taken up by other tissues
- pyruvate can also be used directly by liver and kidney cells to produce energy and CO2
elevations of plasma lactate concentration
clinical link
plasma concentration determined by relative rates of
- production
- utilisation (liver, heart and muscle)
- disposal (kidney)
high levels of lactate can cause problems as it is acidic in the blood
hyperlactaemia
- 2-5mM ie more production than disposal
- below renal threshold
- no change in blood pH due to buffering capacity
lactic acidosis
- above 5mM
- aboe renal threshold
- blood pH lowered
- alter protein function, loss of cardiac contractility and loss of circulatory control
⇢ critical marker in the acutely unwell patient
explain the biochemical basis of the clinical conditions of galactosaemia
mechanism for cataracts on different card
a person cannot break down the sugar present in milk into glucose and is due to a lack of one of: galactokinase, uridyl transferase, or UDP galactose epimerase
- lack of uridyl transferase (most common) causes the most severe symptoms as it is due to accumulation of galactose and galactose-1P
- galactose build-up causes it to enter alternative pathway and get reduced → galactitol (by aldose reductase). This reaction depletes some tissues of NADPH.
- accumulation of galactose-1P affects liver, kidney + brain (could be due to sequestration of Pi, making it unavailable for ATP synthesis)
- causes cataracts and glaucoma in some patients (mechansim on next card)
treatment is the removal of lactose from the diet
evidence is galactose and galactitol present in the urine
why do galactosaemic patients develop eye problems?
- galactose builds up
- enters alternative pathway, gets reduced to form galactitol by aldose reductase
- involves NADPH → NADP+
- this depletes some cells of NADPH
- cross linking of lens proteins by disulfide bond formation causes cataracts
- in addition, accumulation of galactose and galactitol in the eye lead to increased intro-ocular pressure which causes glaucoma
- if goes untreated, glaucoma can cause blindness
explain why the pentose phosphate pathway is an important metabolic pathway in some tissues
important pathways in tissues such as the liver, RBCs and adipose tissue
the major functions of the pathway are to…
produce NADPH
- in cytoplasms
- provision of reducing power for anabolic processes such as lipid synthesis (liver and adipose).
- in RBCs, maintains free -SH groups on cysteine residues in certain proteins
- involved in various detoxification mechanisms that protect cells against toxic chemicals
produce the 5C sugar ribose
- for synthesis of nucleotides (for DNA and RNA)
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1 - Nutrition, Diet + Bodyweight25
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2 - Carbohydrates30
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3 - Carbohydrates + Energy Production23
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6.1 - Haematology 141
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6.2 - Blood Count and Films30
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7.1 - Anaemia40
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7.2 - Anaemia II29
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8.1 - Haemoglobinopathies18
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8.2 - Haemolytic Anaemias11
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8.3 - Myeloproliferative + Other Blood Disorders23
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10.1 - Endocrine Pancreas28
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10.2 - Diabetes Mellitus19
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11.1 - Hypothalmic Pituitary Axis + Growth Hormone30
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14.1 - Thyroid Gland35
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14.2 - Metabolic + Endocrine Control During Special Circumstances36
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12.1 - Adrenal Glands + RAAS System27
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4.2 - Protein + AA Metabolism30
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13.1 - Thyroid Gland Dysfunction23
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9.2 - Endocrinology + Endocrine Control Of Appetite29
