1
Q
I-cell Disease (Mucolipidosis II)
A
- Defective UDP-N-acetylglucosamine-1-phosphotransferase
- Hydrolases secreted (because mannose is not phosphorylated in golgi)→ misshapen bones, clouded corneas, restricted joints, and hyperplastic gums, “gargoyle facies”
2
Q
Ornithine Transcarbamylase Deficiency
A
- Urea cycle disorder → hyperammonemia and increased orotic acid excretion in urine
- Treat by limiting protein intake so that excess ammonia is not produced, eat just enough to get essential amino acids
(Carbomoyl Phosphate Synthetase and N-acetyl glutamate are in the step before and will not produce excess orotic acid)
3
Q
N-Acetylglutamate
A
- Essential to activate carbamoyl phosphate synthase (CPS1) in Urea cycle
4
Q
Dihydrobiopterin Reductase Deficiency
A
-Low BH4 (which is needed for conversion of tyrosine –> DOPA by tyrosine hydroxylase)
- BH4 needed as cofactor for synthesis of Tyrosine, DOPA, serotonin, and NO
(in pathway for both Phenylalanine and Tryptophan)
5
Q
Menke’s Disease
A
Kinky hair disease, low copper
6
Q
Fructose 2,6 bisphosphate
A
- Fructose 2,6 bisphosphate activates glycolysis by inducing PFK1 and inhibiting fructose 1,6 bisphosphatase to stop gluconeogenesis
- Fed: PFK2 makes fructose 2,6 and also activates PFK1 to go towards glycolysis
- Starved: FBP makes fructose 2,6 go to fructose 6 towards gluconeogenesis
[Insulin increases Fructose 6P promoting PFK2 activity –> fructose 2,6, bisphosphate and glycosysis]
7
Q
Splice Sites
A
GT at 5’ (GU in RNA) and AG at 3’
8
Q
Supplementation for Children w/ Measles
A
Vitamin A
9
Q
Aldose Reductase
A
Contributes to buildup of product in eye → cataract
- Glucose to sorbitol
- Galactose to galactitol
10
Q
Fructokinase Deficiency vs Aldolase B Deficiency
A
Fructokinase deficiency: benign fructosuria
Aldose B: severe fructose intolerance w/ hypoglycemia
11
Q
Pyrimidine Dimer Removal by:
A
Nucleotide Excision Repair
12
Q
Reactions requiring Pyridoxine (B6)
A
Transamination reactions or Decarboxylation
13
Q
Hartnup Disease
A
- Defective amino acid transport → diarrhea, dementia, dermatitis (resembles pellagra/niacin deficiency)
- Malabsorption of tryptophan (aromatic neutral AA’s) → aminoaciduria
- Treat with Niacin (B3)
14
Q
Fanconi Syndrome
A
Generalized aminoaciduria (all amino acids)
15
Q
Calories
A
Proteins: 4
Carbs: 4
Fats: 9
16
Q
Blotting
A
SNoW DRoP
- Northern: RNA
- Southern: DNA
- Western: Protein
- Southwestern: DNA binding proteins (e.g. transcription factors, histones, nucleases)
17
Q
Maple Syrup Urine Disase
A
- Impaired degradation of isoleucine, leucine, and valine
- Burnt sugar smell in diaper
18
Q
Niemann-Pick Disease
A
- Sphingomyelinase deficiency
- Progressive neurologic deterioration
- Cherry Red Spot
19
Q
Lesch-Nyhan Syndrome
A
HGPRT deficient → defective pruine salvage → hyperuricemia/gout, self-mutilation, retardation, dystonia
- Because of failure of the purine salvage pathway → de novo purine synthesis must increase to replace the lost bases → PRPP amidotransferase activity will increase
20
Q
GLUT4 and GLUT2 Transporter
A
GLUT4 transporter: insulin dependent (increases translocation to cell membrane); skeletal muscle and adipose tissue
GLUT2: regulates insulin release; hepatocytes
21
Q
Niacin (B3)
A
- NAD+ constituent
- Tryptophan is a precursor
- Flushing
22
Q
Homocystinuria
A
- May resemble Marfan’s (long limbs, tall, subluxation of lenses) but also has mental retardation
- Buildup of methionine (homocysteine is remethylated by salvage pathway)
- Cystathionine synthase deficiency
23
Q
RNA Polymerases
A
I: rRNA
II: mRNA
III: tRNA
24
Q
Mitochondrial Myopathy
A
Ragged red fibers and Gomori trichrome
- Mitochondrial inheritance (maternal); heteroplasmy
25
Kreb's Cycle: NADH, FADH, GTP production
```
NADH made:
- Isocitrate to a-ketoglutarate
- a-ketoglutarate to succinyl coA
- Malate to oxaloacetate
FADH made:
- Succinate to fumarate
GTP made:
- Succinyl CoA to Succinate
```
26
Exclusively Ketogenic Amino Acids
Lysine and Leucine
27
Amino Acid binding site on tRNA
CCA at 3' end
28
Apolipoprotein: A1
LCAT activation (esterification of cholesterol)
29
Apolipoprotein: B48
Chylomicron assembly and secretion by intestine
| Produced by intestinal enterocytes (Truncated form of ApoB100)
30
Apolipoprotein: B100
LDL uptake by extrahepatic cells
| Produced by hepatocytes
31
Apolipoprotein: CII
LPL activation
32
Apolipoprotein: E3 & E4
VLDL and chylomicron remnant uptake by liver
33
mRNA Stop Codons
UGA, UAG, UAA
- Binds releasing factor
- Last amino acid will be the codon before
34
Thiamine (B1) required for:
- Pyruvate dehydrogenase
- Transketolase (part of PPP)
- a-ketoglutarate dehydrogenase
- Branched-chain
35
PPP (Pentose Phosphate Pathway)
- HMP Shunt
- Takes place in the cytosol (e.g. Ketolase)
- G6PD enzyme
- Produces NADPH
36
Mitochondrial Processes
- Beta oxidation of FAs
- Ketogenesis
- Krebs cycle
- Parts of urea cycles
- Pyruvate carboxylation
- Parts of heme synthesis
37
Phenylalanine Conversions
Phenylalanine (via tyrosine hydroxylase) → tyrosine:
- Tyrosine → DOPA → dopamine
- Tyrosine → homogentisate →→→ fumarate
38
Propionic Acidemia
Propionic acid buildup due to propionyl CoA carboxylase deficiency which converts it to methylmalonyl coA
- Val, Ile, Met, Thr
- Odd chain FA’s
- Cholesterol branches
39
LAC Operon: Lactose binds ____
- Lactose binds repressor preventing it from binding the operon
40
______ converts Pro-carcinogens into Carcinogens
CYP450s (microsomal monooxygenase)
41
LAC Operon: Repressor binds _____
- Repressor binds operon (not promoter)
42
LAC Operon: RNA pol binds _____
- RNA pol binds promoter
43
LAC Operon: cAMP-CAP binds _____
- cAMP-CAP binds upstream of promote
44
LAC Operon: Glucose Present
- If glucose is present, it decreases adenylate cyclase --> decreases cAMP --> decreased expression of lac operon proteins
45
P-Bodies
mRNA is processed in nucleus (introns removed, capped and tailed) and enters cytoplasm where P bodies regulate translation and degradation of mRNA
46
When pH > pKa:
H+ protons dissociate
| Eg. At 7.4 pH, pKa 2.2 (COOH would be COO-)
47
When pH
H+ protons bind
| Eg. At 7.4 pH, pKa 10.2 (NH2 would be NH3+)
48
Hyperchylomicronemia (I)
- Very high level of chylomicrons (milky)
| - May develop pancreatitis due to hypertriglyceridemia due to LPL deficiency
49
Familial Hypercholesterolemia (IIA)
Tendon xanthomas and xanthelasmas (eye-lids)
50
tRNA: D arm and T arm Function
- Close to 90 nucleotides in length of non-coding RNA
- D arm: has dihydrouracils, used to recognize the correct aminacyl tRNA synthetase
- T arm: has a sequence needed for tRNA to bind ribosome
51
Methylmalonyl-CoA to Succinyl-CoA requires ______
```
B12 only (isomerization reaction)
- defects in this reaction lead to methylmalonic acidemia
```
52
7-a-hydroxylase
Converts cholesterol into bile acids (decreasing chance of gallstone formation)
53
B-glucoronidase
Released secondary to infection by injured hepatocytes and bacteria → hydrolysis of bilirubin glucoronides → increased unconjugated bilirubin in bile
- Increased risk of Brown pigment gallstones
54
PABA
Folic acid precursor in prokaryotes; Huamns cannot convert it to folic acid, so need dietary folic acid
55
Pyruvate Dehydrogenase & a-Ketoglutarate Dehydrogenase Require Co-factors:
B 1, 2, 3, 5 and lipoic acid
| - Lipoic acid inhibited by arsenic
56
Biotin (B7) required for:
- Pyruvate to OAA
- Acetyl CoA to Malonyl CoA
- Propionyl CoA to Methylmalonyl CoA
57
ETC Complex Inhibitors
Complex 1: Rotenone
Complex III: Antimycin A
Complex IV: CO, Cyanide
Complex V (ATP synthase): Oligomycin
58
Neonatal E. Coli Sepsis with ______
Classic Galactosemia
59
Urea Cycle: 3 Types
- Carbamoyl Phosphate synthetase 1
- N-acetylglutamate cofactor
- Ornithine Transcarbamylase
60
Homocystinuria: 3 Types
- Cystathionine synthase deficiency
- Decreased affinity for PLP (B6)
- Homocysteine methyltransferase deficiency
61
Cystinuria
- Hereditary defect in amino acid transporter
- Cysteine, Ornithine, Lysine, Arginine (COLA)
- Cysteine stones (hexagonal)
62
Niacin (NAD+) can be synthesized endogenously from _______
Tryptophan
63
Vit A Overdose
- Intracranial edema
- Skin changes
- Hepatosplenomegaly - It is also a teratogen
64
Cells that cannot use Ketone Bodies
RBC’s: lack mitochondria
| Hepatocytes: lack succinyl Coa acetoacetate CoA transferase (thiopherase)
65
Refsum Disease
Defect in peroxisomal alpha oxidation → neurologic disturbances due to phytanic acid accumulation
- Treat by avoiding chlorophyll in diet
66
Peroxisomes break down ________
Very long chain fatty acids & fatty acids w/ branch points at odd number carbons that cannot undergo beta oxidation in mitochondria
67
Glycerol Kinase
- Liver specific enzyme
- Glycerol is phosphorylated by G3P
- Only the liver can use glycerol produced by triglyceride degradation via hormone sensitive lipase
68
Detect a Reducing Sugar w/ _______
Copper reduction test (eg. for fructose)
69
Homeobox genes
Code for transcription regulators (role in morphogenesis)
70
Hyperammonemia depletes:
- A-ketoglutarate: causing inhibition of Krebs cycle
| - Glutamate: causing glutamine accumulation → astrocyte swelling/dysfunction
71
DNA laddering
Due to apoptosis: DNA fragments appearing in multiples of 180 bp due to cleavage by endonucleases
72
Palmitoylation
Increases protein hydrophobicity by anchoring receptor carboxyl tails to the plasma membrane
73
Beta oxidation
First step is done by acetyl coa dehydrogenase
- Done in states of starvation
- Impaired if hypoglycemia is seen with low ketones
74
Allelic Heterogeneity
Different mutations in the same locus cause similar phenotypes
75
Prader Willi
Father deleted, mother silenced
76
Angelman
Mother deleted, father silenced
77
Cellular differentiation is determined by _________
Transcription factors
78
Gaucher
Glucocerebrosidase deficiency, wrinkled tissue paper cells
| - Bone pain, thrombocytopenia, anemia, hepatosplenomegaly, etc.
79
Transformation
Naked DNA from environment
80
Transduction (specialized or general):
Via a bacteriophage
81
Mutations in HOXA-13
Hand, foot, genital (HFG) syndrome
82
Amanita
(in mushrooms) inhibits RNA pol II (which stops production of mRNA)
83
CFTR Mutation
3 bp deletion, degraded post-translationally
84
BH4 (tetrahydrobiopterin) cofactor needed for:
Synthesis of phenylalanine into tyrosine, DOPA, serotonin, and NO
85
Amino acid that makes NO
Arginine
86
Amino acid that makes NH3/Urea
Aspartate
87
Recombination vs Phenotype Mixing vs Reassortment
- Recombination: exchange of genes between 2 chromosomes, progeny will have traits from both parent viruses
- Phenotypic mixing: coinfection, nucleocapsid proteins from one strain on another (w/ original genetic material), not passed to progeny
- Reassortment: Viruses mixing segmented genomes
88
TNF-a and Insulin
Cytokine that induces insulin resistance through phosphorylation of tyrosine kinases
89
Deficiency of Arginase
Buildup of Arginine may be due to deficiency of arginase which is needed to make urea
90
Arginine
- Used alone to make NO
| - Also in cycle for Urea
91
NADH and Glucose in setting of Alcohol
NADH High
| Glucose Low
92
Fabry Disease
- a-galactosidase A deficiency
- Peripheral neuropathy, angiokeratomas on lower abdomen, and cardio/renal disease
- ceramide trihexoside buildup
- X-linked recessive
93
Lead Poisoning
Colicky abdominal pain, Bluish line on gums (lead line), wrist or foot drop, microcytic anemia w/ basophilic stippling
94
Repressor binds _______
the operator
95
Kozak sequence mutation
- Aw/ thalassemia intermedia (beta globin gene mutation)
- Plays a role in initiation of translation
- mutation that is upstream of the AUG start codon will interfere with mRNA binding to ribosomes
96
_____ required to keep glycolysis (anaerobic metabolism) going
NAD+
| replenished by conversion of pyruvate to lactate
97
Segments of alpha helices with many hydrophobic amino acids
Usually transmembrane (membrane spanning) protein
98
Orotic Acid in Urine
Either:
- Urea Cycle problem: Ornithine Transcarbamylase (the carbamoyl phosphate gets converted to orotic acid)
- Pyrimidine Pathway problem: megaloblastic anemia
99
Kernicterus
Unconjudated (water insoluble) bilirubin cannot be excreted so it deposits in the brain
- aw/ crigler-najjar
100
Organophosphates
Irreversible Cholinesterase Inhibitors
| Tx: pralidoxime which reactivates cholinesterase and atropine
101
16S rRNA in Prokaryotes
Part of the 30s ribosomal subunit
- contains a sequence complementary to the Shine Delgarno Sequence on the mRNA
- binding is necessary of initiation of protein translation
102
PNMT
Induced by cortisol to convert NE to E
103
Steps of Base Excision Repair
Glycosylase (recognizes abnormal base), Endonuclease (cleaves), Lyase (extracts), Polymerase (fills), Ligase (seals)
104
Squamous metaplasia of specialiszed epithelia to a keratinizing epithelium
Vitamin A deficiency
| eg. in someone w/ cystic fibrosis, may see squamous metaplasia of pancreatic exocrine ducts
105
Primers to make complementary DNA
DNA pol only synthesizes in 5-3' direction
| and complementary DNA runs antiparallel
106
McArdle Disease
Muscle pain and weakness w/ decreased exercise tolerance
Myophosphorylase deficiency (needed for glycogenolysis)
No hepatomegaly
107
CAAT and TATA boxes
Promoters of transcription in eukaryotic cells (located upstream form transcription start size)
108
Step in Cycle where Urea is Made
Arginine to Ornithine (releases Urea)
109
7 alpha-helical transmembrane proteins
typically G protein coupled receptors (GPCR)
| composed of hydrophobic amino acids
110
Non-polar/Hydrophobic amino acids
Glycine, Alanine, Valine, Leucine, Isoleucine, Phenylalanine, Tryptophan, Methionine, and Proline
111
Bloom Syndrome
Photosensitivity, short stature, erythema, and telangectasias
- defect in DNA helicase gene RecQL3
- predisposed to lymphoproliferative and GI malignancies
112
RFLP Procedure
Identifies presence of disease causing mutations or identifies people based on normal variation in genome by restriction site cleaving
- SNPs are the more common cause of a RFLP
113
Defective Proline Hydroxylation during Collagen Synthesis
Leads to failure of Triple Helix formation and stabilization by pro-alpha chains during collagen synthesis
114
MCAD defciency
AR, inability to degrade medium length fatty acids by beta oxidation
- hypoketotic hypoglycemia and neurologic and hepatic dysfunction after fasting or increased metabolic stress
- Heterozygotes have decreased MCAD activity but phenotypically normal
115
Short 30 amino acid alpha helical protein fragment w/ leucin residues at every 7th position
Most likely part of a leucine zipper dimerization
| Allows for binding to DNA
116
CPSII (Carbamoyl Phosphate synthase II)
Catalyzes initial step in pyrimidine synthesis
| - located in cytosol
117
MODY (Maturity Onset Diabetes of the Young)
- Mutation in glucokinase that decreases its affinity for glucose
- glucokinase is a glucose sensing device in pancreatic beta cells (needs a high concentration of glucose to be activated)
118
Von Gierke Disease
- Deficiency of Glucose 6 phosphatase (glycogen storage disease) --> impaired release of free glucose generated from glycogenolysis and gluconeogenesis
Hepatomegaly and steatosis
Fasting hypoglycemia and lactic acidosis
Hyperuricemia and hyperlipidemia
119
Cori Disease
Defciency of debranching enzyme (glycogen storage disease)
- hypoglycemia, hepatomegaly, muscle weakness
- lots of limit dextrins
120
Pompe Disease
- deficiency of lysosomal enzyme alpha 1,4 glucosidase (acid maltase) [glycogen storage disease]
- Severe cardiomegaly
- Glycogen accumulation in lysosomes
121
Alkaptonuria
AR defect in homogentisic acid oxidase
- can't break down phenylalanine or tyrosine and build up homogentisic acid
- urine turns black with standing, HGA deposits in cartilage, sclera, and dermia (black blue color)
- longstanding disease --> develop ochronosis (darkening of tendons) and arthropathy; brown sclera
122
Malonyl CoA Buildup
Malonyl-CoA inhibits the rate-limiting step in the beta oxidation of fatty acid
- resting muscle requires less energy (and thus less need for fatty acid breakdown) than active muscle
123
Congenital Intolerance to Breast Milk
- galactosemia, in which the body cannot convert galactose to glucose
(resulting in an accumulation of Galactose 1-phosphate)
Lactose (the disaccharide in milk) is composed of glucose + galactose
124
Niacin (B3) Made From:
Tryptophan and requires B2 and B6
125
Galactosyl B-1,4-glucose
Lactose
| its breakdown to glucose and galactose by Lactase in low in lactase deficiency
126
Conversion of Pyruvate to Lactate
Serves to re-oxidize NADH into NAD in the absence of oxygen in order to keep doing Glycolysis (since it cannot do Krebs without O2)
127
Rb Hyperphosphorylation
Rb is inactivated so cell can transition from G1 to S phase and start proliferating
128
Arsenic Inhibits:
Lipoid Acid which is needed as a cofactors for Pyruvate dehydrogenase (to enter TCA) and also alpha ketoglutarate dehydrogenase
- garlic breath, rice water stool, And vomiting
129
Pyruvate shunted to alanine and lactate in:
Pyruvate dehydrogenase deficiency
- can't do TCA, Neuro defects, lactic acidosis, and high serum alanine
- need to have a ketogenic diet (lysine, leucine)
130
Euglycemia during fasting maintained by: 3 organs
Primarily liver, but also kidney and intestinal epithelium
131
VLDL
TGs to periphery
132
IDL
TGs to Liver
133
LDL
Cholesterol to periphery
134
HDL
Cholesterol to liver
135
Type I hyperchylomicronemia Defect
ApoCII mutation or LPL deficiency
136
Type IIA familial hypercholesterolemia
LDLR deficiency
137
Type IV Hypertriglyceridemia
VLDL overproduction
Quick Notes for Step 1
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