Biochem Flashcards
1
Q
Orotic aciduria
A
- AR Deficiency in UMP synthase needed for the conversion of orotic acid to UMP (for de novo pyrimidine synthesis)
- High orotic acid in urine, megaloblastic anemia, NO HYPERAMMONEMIA
- OTC deficiency (acc. of carbamoyl phosphate) XLR, MC urea cycle d/o
Similar symptoms w/ hyperammonemia, no megaloblastic anemia
Tx: Oral Uridine (converted to UMP and inhibits CPS 2, decr orotic acid)
2
Q
Adenosine Deaminase Deficiency
A
- AR Deficiency in adenosine deaminase, enzyme needed to met/convert adenosine into inosine.
- Acc. of ATP and dATP cause feedback inhibition of ribonucleotide reductase –> prevents DNA synthesis.
Affects labile cells (i.e. lymphocytes) AR SCID
3
Q
Lesch- Nyhan Syndrome
A
-XLR Deficiency in HGPRT- enzyme needed for purine salvage (hypoxanthine –> IMP and guanine –> GMP).
Results in excess uric acid prod and de novo purine synth.
Symptoms: self-mutilation (lip biting), retardation, aggression, hyperuricemia, gout), dystonia, writhing
Tx: allopurinol or febuxostat
4
Q
p53 and Cancer
A
-p53- a TF involved in activating DNA repair enzymes and apoptosis. -Regulates the cell cycle at G1 to S progression. -Regulated by mdm2 (ubiquitin ligase)/DNA dmaage
5
Q
Rb and Cancer
A
-Rb is a tumor suppressor protein involved in inhibiting cell cycle TFs (i.e. E2F) and chromatin remodeling. -Regulates the cell cycle at G1 to S progression.
6
Q
Xeroderma Pigmentosa
A
* Small child with multiple skin lesions (squamous cell carcinoma, melanoma, and basal cell carcinoma) and severe sensitivity to sunlight. AR inheritance * Mutation in nucleotide excision repair ; unable to repair UV-induced thymidine dimer formation.
7
Q
Hereditary nonpolyposis colorectal cancer (HNPCC)
A
* Predisposes to CRC w/o polyp hx (proximal/left colon) and endometrial hyperplasia * Defect in nucleotide mismatch repair. AD inheritance. * Microsatellite instability
8
Q
Ataxia Telangiectasia
A
* Triad: * Cerebellur defects (i.e. ataxia) * IgA deficiency (intestinal AB) Increased susceptibilty to leukemia and lymphoma due to chromosome instability Caused by a defect in the ATM gene that codes for double strand break repair enzyme (repairs via Non-homologus end-joining). AR inheritance
9
Q
Osteogenesis imperfect (Type 1 collagen)
A
-Deficiency in Type 1 procollagen formation (triple helix formation) - Bone, skin, tendon, and wound repair -Multiple bone fractures, blue sclerae (translucent CT layer over choroid), hearing loss (abnormal middle ear bones), dental imperfections (lack of dentin) -Type 2 collagen OI is embrylogically lethal
10
Q
Scurvy
A
-Deficiency in Vit C (absorbic acid); impaired hydroxylation of proline and lysine residues in collagen 1-4 needed for crosslinking and stabilization -malaise/lethargy,spongy/bloody gums, skin petichiae and brusing (thighs),
11
Q
Ehlers-Danlos syndrome (Type 3 collagen)
A
-Deficiency in type 3 collagen (reticulin) synthesis; impaired clevage -Skin, vasculature, uterus, etc. -Hyperextensible skin and joints, easy bruising, berry aneurysms
12
Q
Alport syndrome (Type 4 collagen)
A
-Deficiency in Type 4 collagen synthesis (XR) -Basement membrane in kidney, ears, and eyes. -Nephritis, deafness, and blindness
13
Q
Marfan’s syndrome
A
-Deficiency in fibrillin gene- the structural component of elastin -long/slender limbs, kyphosis/scoliosis, osteoarthritis, poor eyesight and hearing
14
Q
Chediak-Higashi syndrome?
A
-Deficiency in LYST gene; impairs MT polymerization needed for trafficking phagolysosomes to the lysosome and axoplasmic neuronal transport -recurrent bacteiral infections, albinism, peripheral neuropathy
15
Q
Kartagener’s Syndrome
A
-Deficiency in the production of dynein- an ATPase that links peripheral MT doublets and allows for cilium sliding and cilia bending -Male and female infertility, recurrent sinusitis (failure of resp. tract outward movement) - Assoc. with situs inversus
16
Q
GLUT transporters (5)
A
1 RBCs, blood brain barrier 2 Liver, small intestine. pancreas. High capacity, high Km (low affinity). Liver eats last. - Insulin-mediated glucose uptake 3 Neurons, placenta, testes. Low Km (high affinity) 4 Muscle, fat and heart. -Insulin-mediated glucose uptake 5 Fructose transporter
17
Q
Insulin vs. Glucagon
A
**- Glucagon/Epi; kinase **
- (incr cAMP –> incr PKA)
- Glycogen phosphorylase (glycogenolysis)
- Adipose lipase (FFA release)
- Gluconeogenesis
- Insulin; phosphatase
- (Tyr kinase dimeriz. –>inc. protein phosphatase)
- Glycogen synthetase (glyconeogenesis
- Lipid/protein catabolism
- GLUT2 and 4 uptake
18
Q
Hexokinase vs Glucokinase
A
- Responsible for phosphorylating **glucose –> G6P **
- Glucokinase is only in the liver and pancreas
- Glucokinase has higher Km (MM constant) and high Vmax
- Glucokinase has lower affinity for glucose
- Glucokinase is not inhibited by G6P
19
Q
Pyruvate dehydrogenase deficiency
A
* Nuerological defects (less ATP prod.) and lactic acidosis ( increased pyruvate) * Congenital or in alcoholics (B1 deficiency) * Tx: 2 ketogenic amino acids (won’t inc. lactic acid): Leucine and lysine
20
Q
Pyruvate metabolsim
A
- Pyruvate –> alanine (ALT). For NH4+ transport following amino acid catabolism.
- Pyruvate –> oxaloacetate (pyruvate carboxylase). For gluconeogenesis or TCA replenishment.
- Pyruvate –> Lactate. For E in RBCs.
- Pyruvate –> Acetyl CoA (pyruvate dehydrogenase). For TCA cycle.
- Regulated by NADH:NAD+ ratio
21
Q
Ethanol metabolism
A
- Met. of ethanol in liver produces NADH
- High NADH:NAD+ ratio –> lactic acid production (NAD+ is the LR in ethanol met)
- High lactate
- Met. acidosis with resp. comp. (high anion gap)
- Low glycerol-3-phos
- Low pyruvate levels = no gluconeogenesis
- High FA synthesis (Fatty liver)
22
Q
Krebs cycle
A
* Citrate synthetase inhibited by ATP * Citrate: * Inhibts PFK1 (RLE of glycolysis) * Activates Acetyl CoA Carboxylase (RLE of FA synthesis)
23
Q
Metabolic disorders
A
- Glycolysis -Fructose met (Liver) - Galactose met (Liver) - Amino acid/Urea met - FA met - Glycogen storage disease - Lysosomal storage disease - Dyslipidemias
24
Q
Disorders of fructose metabolism (sucrose = glucose + fructose)
A
- **Essential fructosuria **
- Deficiency in fructokinase (AR)
- Asymptomatic; found in blood and urine
- Fructose intolerance
- Deficiency in Aldolase B (AR)
- Hypoglycemia, jaundice, liver cirrhosis
- Acc. of F1P–>dec. intracell Phos–> inhib.glycogenolysis/gluconeogenesis
25
Disorders of galactose metabolism (lactose = glucose +galactose)
- **Galactokinase deficiency** (AR)
- Galactose in blood and urine (from breast milk)
- Infant cataracts; no object tracking or smile
- Aldose reductase act.--\> Acc. of galactitol
- **Classic Galactosemia**
- Deficiency in galactose 1 phos uridyltrans. (AR)
- Failure to thrive, jaundice, infant cataracts
- Aldose reductase act.--\> Acc. of galactitol
- Acc. of F1P--\>dec. intracell Phos--\> inhib.glycogenolysis/gluconeogenesis
26
Aldose reductase
- Glucose --\> sorbitol--\> fructose
- Alt. method of trapping glucose ( hyperglycemia )
- Lens and neurons = no sorbitol dehydr. enzyme
- Sorbitol acc. --\> osmotic damage (i.e cataracts, retinopathy, and nueropathy)
- Galactose --\> galactitol
- Galactitol acc. --\> osmotic damage (i.e cataracts)
27
Essential amino acids (glucogenic aa vs. ketogenic aa)
**Glucogenic**: converted into pyruvate or TCA intermediates
- Methionine, Valine, Histidine+
- Arg and His only essential during devel
**Ketogenic**: converted into acetyl CoA --\> ketone bodies (acetoacetic acid and B-hydroxybutyric)
-Leucine and Lycine+
**Both**: Ile, Phe, Thr, Trp
28
Amino acid catabolism (fasting state; aspartate)
Allows muscle to use AAs as energy
1. **Muscle protein breakdown**.
2. **Muscle transamination**:
- Aspartate + a-KG--\>OAA+Glutamate (AST)
- Glutamate + Pyruvate--\> a-KG + Alanine (ALT)
Alanine transported in blood to liver
3. **Liver transamination**:
- Alanine + a-KG --\> Pyruvate + Glutamate (ALT)
- Pyruvate --\> Glucose (Gluconeogensis)
- Glutamate --\> NH4+ (Glutamate dehydrogenase)
29
Amino acid catabolism (fasting state; glutamate)
1. Muscle protein breakdown. 2. Peripheral issue transamination: -Glucogenic aa+a-KG--\>Oxaloacetate+ Glutamate (exits) -Glutamate + NH4+ --\> Glutamine (Glutamine syn) 3. Liver transamination: -Glutamine --\> Glutamate + NH4 (Glutaminase) - Glutamate --\> NH4+ (Glutamate dehydrogenase)
30
Hyperammonemia
\* Tremor, slurring of speech, blurred vision \* Deficiency in urea cycle enzyme. Results in excess NH4+ --\> depletes a-KG --\> inhibits TCA \* Acquired (liver disease) \* Hereditary Tx: Benzoate or phenylbutyrate (bind aa)
31
Ornithine transcarbamoylase deficiency (OTC)
XLR, MC urea cycle disorder. OTCase in mito, necessary for production of citrulline from ornithine and CP
- Results in acc. of cabamoyl phosphate --\> inc. orotic acid by UMP synthase (intermediate in pyrimidine syn)
- orotic acidemia (presence in blood and urine), decr. BUN, hyperammonemia (tremor, slurred speech), irritability, poor muscle tone, seizure
32
ETC
\* Recieves donated e- from oxidized carriers (NADH, FADH2) \* 4 complexes + CoQ + Cytochrome C \* Poisons: \* ETC inhibitors (CN-, CO) \* Uncoupling agents (Aspirin, brown fat)
33
CO poisoning
- Headache , cherry-red discoloration (masking cyanosis), seizures. Car exhaust, house fire, etc.
- CO outcompetes O2 for binding to Hb
- inhibition of cytochrome oxidase in ETC.
\*Decreased O2 saturation; normal PaO2, Left shift
34
CN- poisoning
- Headache , cherry red, weakness/lactic acidosis, cardiac arrest, coma/seizures. House fire.
- CN- binds and inhibits cytochrome oxidase in ETC, decreases ATP synth.
\* normal O2 sat, O2 content of venous and arterial blood are essentially same (no extraction of O2 in tis)
\* Tx: **Amyl nitrites** to oxidize Hb to metHb which combines with CN. **Thiosulfate** binds cyanide --\> thiocyanate, renally excreted
35
Salicylates and alcohol on MT
\* Hyperthermia \* Damages inner mt membrane causing uncoupling and heat generation \* Thermogenin/brown fat used to stabilize newborn body temp.
36
HMP shunt
- Requires G6PD and Transketolase
- Provides source of PRPP for nucleotide synthesis (purine and pyrimidine) and
- NADPH for: \* Neutralizing ROI: Glutathione reductase
\* Creating ROI (phagolysosome): NADPH oxidase, Superoxide dismutase, Myeloperoxidase
37
\* Free Radical Injury
-Ionizing radiation -Hydroxyl FRs -Mt damage -Superoxide FRs -High O2 conc. (repurfusion) -Hydroxyl. superoxide, and peroxide FRs (H2O2) -Drugs -Acetominophen FR (fulminant hepatitis) -CCl4 (liver necrosis)
38
Chronic granulomatous disease
-Defiency in NADPH oxidase (X-linked) which is specifically found in PMNs and monocytes. -Test: Serum Nitroblue tetrazolium test (NBT) -Reduced prod. of superoxide (O2) results in absent respiratory burst. Most organisms produce H2O2 which can be used by host to generate HOCl (bleach). -Cat+ organisms (staph) degrade self- produced H2O2. CGD PMNs cannot kill and M0's infiltrate. M0 wall off infection and form multi-nucleate giant cells
39
Myeloperoxidase deficiency
-Deficiency in myeloperoxidase (AR) which is specifically found in PMNs and M0. - Normal respiratory burst (NBT test), but inability to produce HOCl (bleach)-- most potent killer
40
G6PD deficiency
-Hemolytic anemia (H2O2 induced oxidative damage to RBCs). Heinz bodies (aka. bite cells). -Oxidzed, PPT, Hb --\> removed by splenic culling Deficiency in G6PD (X-linked recessive) --\> dec. NADPH --\> dec. reduced Glutathione. - Glutathione necessary for the met. of H2O2 \* Inflammatory H2O2 \* Drug induced H2O2
41
Phenylketonuria (PKU)
AR deficiency of Phenylalanine hydroxylase Conversion of phenylalanine into tyrosine, BH4 cofactor - Mental/growth retardation, seizures, albinism, eczema, musty body odor -TX: Screen at birth. Low phenyalanine diet w/ tyrosine supplements
42
Alkaptonuria
Deficiency in homogenistic acid oxidase (AR, benign) Necessary for degradation of tyrosine to fumarate -Dark CT, brown pigmented sclera, black urine on exp to air, arthralgias
43
Albinism
- Causes: 1. Deficiency in tyrosinase (AR). Enz necessary for the conversion of DOPA --\> melanin. 2. Defective melanocyte tyrosine transporters
44
Homocystinuria
-Defect in Met --\> cytsteine. Caused by: -Deficiency of cystathionine synthase (homocysteine + serine--\>cystathionine...--\>cysteine) -Impaired binding/deficiency of B6 (cofactor)-tx is B6 tx: decr methionine, incr cysteine, b12, folate -Deficiency of homocysteine methyltransferase (methionine synthase-from homocysteine) - B12 cofactor tx: increase methionine in diet - All AR. Excess homocysteine in urine, tall stature,kyphosis, mental retardation, osteoporosis, lens subluxation, thombosis, AS, stroke
45
Cystinuria
AR, defect in PCT and intest AA transporter --\> acc. of cysteine in renal tubules. COLA: cysteine, ornithine, lysine, arginine - all are soluble in urine except cysteine can precip - cystine hexagonal kidney stones, precip at low pH, staghorn -Tx: Acetazolamide (alkalizes the urine in the renal tubules and decreases cysteine ppt) Cyanide-nitroprusside urine test dx
46
Maple syrup urine disease
Deficiency in a-ketoacid dehydrogenase (TLCFN) Isoleucine, Leucine, and Valine -Mental retardation, Maple syrup urine (smell) Leu: us. degraded to acetoacetate and acetyl CoA (ketogenic) Val, Ile: us degraded propionic acid--\>MMA--\>succinyl CoA
47
Hartnup disease
- Hereditary defect in transport of neutral aa across renal tubule/epithelial cells. --\> Increased urinary excretion of Tryptophan. --\> Decreased GI absoroption of Tryptophan. -Dec. Tryptophan --\> dec. Niacin --\> pellagra -Dermatitis, Dementia, Death
48
Von Gierke disease (Type 1 GSD)
- Deficiency in **Glucose-6-phosphatase**- needed for cellular release of glucose
- Infant w/ severe hypoglycemia and lactic acidosis, hypertriglyceridemia, hepatomegaly (high glycogen content)
- impaired gluconeogenesis- no release of glucose from liver!! (Enzyme bypasses glucokinase)
Tx: freq oral glucose, avoid fructose & galactose
49
Pompe Disease (Type 2 GSD)
- Deficiency in **acid maltase** aka **a-1,4 glucosidase**
- a lysosomal enzyme responsible for breakdown. of some glycogen.
- Infant w/ progressive muscle weakness, hepatomegaly, **cardiomegaly **--\> HF, death
50
Cori Disease (Type 3 GSD)
- Deficiency in **debranching enzyme** aka **a-1,6 glucosidase**
- Infant w/ milder hypoglycemia and hepatomegaly, (high glycogen content).
- Normal blood lactate due to intact gluconeogenesis; some glycogen met. by glycogen phosphorylase and released by liver.
Tx: high protein diet to feed gluconeogenesis
51
McArdle disease (Type 4 GSD)
- Deficiency in **myophosphorylase** (skel mm. glycogen phosphorylase)
- Severe, painful, muscle cramps upon exercise, myoglobinuria w/ exertion, arrhythmia from electrolyte abnorm, No increase in lactate after exercise!
- symptoms due to acc. of glycogen in muscle
52
Fabry's disease
- LSD, Deficiency in **α-galactosidase A**
--\> accumulate **ceramide trihexoside** (XLR)
- Periph neuropathy (hands/feet), angiokeratomas, CVD and renal failure
53
I cell disease
- Deficiency in a phosphotranferase results in impaired ability to add mannose-6-phosphate (in golgi) to target lysosomal proteins
- Coarse facial features, clouded corneas, restricted joint movement, and high plasma levels of lysosomal enzymes- FATAL
54
Gaucher's Disease
-LSD, Deficiency in **glucocerebrosidase** aka **ß-glucosidase**
--\> acc. of **glucocerebroside**
- Most common lysosomal storage disease
- Hepatosplenomegaly, pancytopenia, aseptic necrosis of femur/bone, "Gaucher cells" crumpled tissue paper.
55
Niemann-Pick disease
-LSD, Deficiency in **Spingomyelinase**
--\> acc of **spingomyelin**
-Progressive neurodegeneration and death, hepatosplenomegaly, cherry-red macula, foam cells (lipid laden macrophages)
56
Tay-Sachs disease
LSD, Deficiency in **Hexosaminidase A**
--\> acc of **GM2 ganglioside**
-Progressive neurodegeneration and death, developmental delay, cherry-red macula, onion skin lysosomes (lipid laden lysosomes of neurons)
NO hepatosplenomeg
Ashkenazi
57
Krabbe disease
-LSD, Deficiency of **B-galactocerebrosidase**
--\> acc. of **galactocerebroside**
-Peripheral neuropathy, developmental delay, optic atrophy, _globoid cells_
58
Metachromatic leukodystrophy
-LSD, Deficiency in **Arylsulfate A**
--\> acc. of **cerebroside sulfate**, in white matter/periph nn
-Central and preipherial demyelination --\> dementia and ataxia
59
Hurler's Syndrome
- Deficiency of **α-L-iduronidase **
--\> acc. of GAGs (heparan, dermatan & keratan sufates)
-developmental delay, gargoylism (coarse facial features, macroglossia), airway obstruc, corneal clouding, neurologic dysfunction (hearing loss),
Death in 1st decade (Mucopolysaccharidoses)
60
Hunter's Syndrome
- Deiciency of **Iduronate sulfatase**
--\> acc. of GAGs (XLR)
- Mild hurler, Aggressive behavior - NO corneal clouding, slower progress
61
Carnitine deficiency
- Needed to transfer LCFA into the mitochondria for b-oxidation --\> toxic accumulation
- Weakness/hypotonia, hypoglycemic, hypoketotic
62
Acyl-CoA dehydrogenase deficiency (medium chain)
- Deficiency in medium chain acyl-CoA dehydrogenase - mitochondrial enzyme needed for the B-oxidation of FA. (AR)
- hypoglycemia, hypoketotic upon fasting.
- Sudden infant death syndrome.
- Tx: Feedings with slow-release carbs- Cornstarch
63
Cholesterol biosynthesis
-3-hydroxy-3-methylglutaryl (HMG Co-A reductase) converts HMG-CoA --\> mevalonic acid -HMG CoA synthesized from 3 acetyl CoA molec. -Statins (anti-cholesterol drugs) are HMG CoA reductase inhibitors; block skeletal muscle ubiquinone syn. a coenzyme needed for muscle cell metabolism.
64
Lipoproteins and apolipoproteins
- Lipoproteins- Lipid/proteins complexes that are essential for the trans. of cholesterol, TAGs, and fat-soluble vitamins- ADEK) -(chylomicrosn, VLDL, LDL, IDL, HDL) - Apolipoproteins- increase lipoprotein solubility, activate metabolic enzymes, and mediate the binding of lipoproteins to cell-surface receptors - C (LPL cofactor), A (binds liver remnant receptor)
65
Lipid transport -Syn. in liver from mt Acetyl-CoA (released as VLDLs) -Syn. in intestines from dietary TG (released as chylomicrons w/ apolipoprotein B)
• Pancreatic lipase → deg/emulsification of dietary TG in small intestine for packaging. • Lipoprotein lipase (LPL) → deg. of circulating chylomicrons and VLDLs into FFAs or IDLs. 2 paths +Apolipoprotien C (LPL cofactor) • Hepatic TG Lipase (HL) → deg. of chylomicron remnants and IDLs into FFA for liver storage. +Apolipoprotein E (Remnant uptake) • Hormone-sensitive lipase → deg. of TAG stored in adipocytes into FFA (HDL transport).
66
Hyperchylomicronemia (Type 1a/b- Familial dislipidemia)
-A- Deficiency in LPL -B- Deficiency in ApoC (LPL cofactor) -Needed for the breakdown of chylomicrons/VLDLs -Resides in capillary walls of adipose and muscle and cleaves TAGs into FFA and glycerol. -High chylomicron/TAG --\> creamy serum. pancreatitis, hepatosplenomegaly, puritic xanthomas - Normal LDL and HDL
67
Hypercholesterolemia/hyperbetalipoproteinemia (Type 2a/b familial dislipidemia)
-Deficiency in LDL receptor- periph. tissue uptake -Deficiency in ApoB- ligand for LDL receptor binding -High cholesterol (LDL), early atheroscl. disease--\> MI, Achilles tendon xanthomas -TAG levels remain normal (clear serum) -Tx: Fibrates- increase prod. of ApoA --\> inc. activation of cholesterol acetyltransferase (LCAT) which prod. HDLs
68
Hypertriglyceridemia (Type 4 familial dislipidemia)
-Deficiency in VLDL negative feedback mechanism --\> Hepatic overproduction of VLDL- (from excess dietary fats) -High cholesterol (VLDL) and TAG (turbid/foamy plasma), pancreatitis -Tx: Fibrates- increase prod. of ApoA --\> inc. activation of cholesterol acetyltransferase (LCAT) which prod. HDLs
69
Abetalipoproteinemia
-Deficiency in ApoB-- a cofactor needed for chylomicron secretion---\> TAG acc. in enterocytes. (AR) -Failure to thrive, steatorrhea, ataxia, and acanthocytosis -Tx: Vitamin E- helps restore lipoprotien prod.
70
Dysbetalipoproteinemia (Type 3 familial dislipidemia)
- Deficiency in ApoE- ligand for cholesterol remnant hepatic uptake -elevated VLDL levels -Palmer xanthomas (turbid serum); seen with diabetes
71
Hypercholesterolemia and MI
-Subendothelial space accumulates lipoproteins. Lipoproteins get chemically modified (i.e. oxidized) which initiates an inflammatory response and phagocytosis by M0 --\> foam cells. Release of PDGF, TNF, and IL-1 results in recruitment of platelets and production of ECM in the vesseles --\> formation of fibrotic plaque -\> actue MI
72
Unonjugated vs. conjugated hyperbilirubinemia
- Bilirubin is the breakdown product of heme. It is conjugated with a glucoronic acid in the liver to increase its solubility in water
- Unconjugated hyperbilirubinemia - high RBC breakdown or decreased liver function (Gilberts)
- Conjugated hyperbilirubinemia - hepatic obstruction preventing excretion into bile (urine urobilinogen (product of gut flora bilirubin breakdown)
73
Fat soluble vitamins (can accumulate in fat --\> toxic)
- ADEK -A (retinol)- visual pig. and normal diff. of epithelial cells into specialized cell types
- D (D3)- intestinal absorption of Ca2+ and phos.
- E- antioxidant that protects RBCs from FR dam.
- K- catalyzes the carboxylation/act. of clotting factors 2,7,9, and 10.
74
Water soluble vitamins
- B,C, Biotin, and Folate
- B (Thiamine, riboflavin, niacin, pantothenate, pyridoxine, cobalamin)
- C (absorbic acid)- proline hydroxyation in collagen synthesis, dopa --\> NE conversion, Iron absorption
- Biotin (B7) - cofactor for carboxylation enzymes
- Folate (B9) - synthesis of nucleic acids
75
Vitamin B1 (thiamine)
- Cofactor for **dehydrogenase enzymes** (pyruvate dehydrogenase, a-ketoglutarate dehydrogenase, transketolase (HMP shunt), Branched AA dehydrogenase)
- Deficiency impairs glucose met--\> ATP depletion, worsened by glucose infusion, Alcoholics- Primarily affects brain and heart.
- Wernicke-Korsakoff synd - confusion, opthalmoplegia, ataxia, and personality change.
- Beriberi - cardiac failure, DCM, sym. muscle wasting, edema
76
Vitamin B2 (riboflavin)
- FAD, FMN, Cofactor in **redox reactions** (succinate DH in TCA) and prod of FADH2
- Deficiency impairs ATP prod.
- Cheilosis (inflam/scaling of lips)
- Corneal vascularization
77
Vitamin B3 (niacin)
- Derived from tryptophan, synthesis requires B2 and B6
- Constituent of NAD+
- Deficiency results from impaired absorption of tryp. (Hatnup synd), deficiency in B6 (INH), malignant carcinoid syndrome (increased Trp metab)
- Glossitis (tongue inflammation)
- Pellagra (dermatitis, dementia, diarrhea)
- Lowers VLDL, raises HDL, facial flushing (due to PGs), hyperglycemia, hyperuricemia
78
Vitamin B5 (pantothenate)
- Cofactor for acyl transfers (CoA) and FA synthase
- Deficiency is rare
- Alopecia
- Dermatitis
- Adrenal insufficiency
CoA used in synth of vit. A, D, steroids, heme A, fatty acids, amino acids, proteins
79
Vitamin B6 (pyridoxine)
- Cofactor needed for transamination rxns (ALT and AST), decarboxylation rxns, glycogen phosphorylase, and synth of cystathionine, heme, niacin, histamine, and NTs: GABA, 5-HT, Epi, Ne, DA
- Deficiency results in impaired protein metabolism, glucose level maintenance, RBC syn,
- Convulsions/hyperirritability
- Peripheral neuropathy (Induced by INH and OCPs)
- Sideroblastic anemia (impaired Hb synth and iron excess, microcytic hypochromic)
80
Vitamin B12 (cobalamin)
- Cofactor for synthesis of methionine (from homocysteine+folate) and the regeneration of reduced folate
- Deficiency impairs DNA synthesis (though stored in large reserve quantities) and results in neuronal acc. of methymalonic acid
- Macrocytic/megaloblastic anemia
- Peripheral neuropathy/ataxia
81
Vitamin B9 (Folic acid)
-Converted to THF; used as coenzyme for methylation reactions -Deficiency impairs DNA/RNA synthesis (small reserve store; depleted in alcoholics & pregnancy) -Macrocytic, megaloblastic anemia -Neural tube defects
82
Biotin
-Cofactor for carboxylation enz. (pyruvate carb., Acetyl CoA carbox., Propionyl CoA carboxylase - Deficiency in rare (caused by excessive egg consumption) impairs gluconeogenesis, FA synthase regulation and DNA syn. -Dermatitis/enteritis -alopecia
