Notes

Tuesday, 27 January 2015 6:31 pm

1. HMG CoA reductase inhibitors cases rhabdomyolysis:

a. HMG CoA reductase inhibitors reduce synthesis of mevalonate >> farnesyl. Farnesyl = component
of CoQ. This reduction of farnesyl leads to ETC disruption and cessation of ATP synthesis.
b. Hence cellular swelling and myocyte rupture
c. Eg. Simvastatin, atorvastatin, rosuvastatin

2. HMG CoA synthase:

a. Two isozymes in liver parenchyma:
a. Cytosolic - responsible for Cholesterol synthesis
b. Mitochondiral - responsible for ketone body synthesis

3. Cholesterol synthesis:
a. Producing one molecule of IPP = 3ATP
b. Squalene synthesis = 2 molecules of Farnesyl pyrophosphate [3ATP x 3] + NADPH
c. HMG CoA reductase:
a. Upregulated by insulin and thyroxine
b. Downregulated by glucagon and corticosteroids

4. Cholesterol reuptake is by receptor mediated endocytosis

5. Smith Lemli Opitz syndrome:
a. AR
b. Partial deficiency in 7-dehydrocholesterol-7-reductase
c. Reduces 7-DHC to cholesterol
d. Associated with holoprosencephaly

6. Tangiers disease: Deficiency of ABCA1; no efflux of Cholesterol from peripheral tissues into HDL

7. Reverse Cholesterol transport:

a. Peripheral CH --> CE by LCAT
a. LCAT activated by Apo A1
b. HDL3 --> HDL2 (cholesterol ester rich)
b. CE given to VLDL in exchange for TG --> LDL --> Absorbed into liver
c. HDL2 binds to SRBB1 (liver) --> Uptake of whatever cholesterol esters are present; leaves behind
HDL3 in its place

8. Essential fatty acid deficiency:

a. Linoleic acid (or Arachidonic acid)
b. Linolenic acid
c. Dry scaly dermatitis

9. Pantothenic acid:
a. Component of CoA
b. Attached to Fatty acid synthase as 4 phosphopantetheine

10. Acetyl CoA carboxylase - catalyzes first step in fatty acid synthesis; naturally inhibited during fasting

11. Carnitine deficiency - you cant make ketone bodies

a. Acyl carnitine transporter is damaged, hence fatty acids cant be transported into the mitochondria
from the cytosol
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 from the cytosol
b. CPT-1 and CPT-2 deficiency (Carnitine palmitoyl transferase):
a. Presents with muscle weakness + myoglobinuria following exercise
b. Severe hypoglycemia, coma on fasting

12. Tryptophan --> Niacin

13. Biotin:
a. CO2 carrier hence cofactor for carboxylase enzymes
b. Eating too much egg white leads to deficiency:
a. Avidin (egg white protein) binds to biotin.
c. Deficiency:
a. Failure of gluconeogenesis (Pyruvate carboxylase)
i. Mitochondrial enzyme
ii. Pyruvate --> OAA failure
iii. Lactic acidosis
b. Build up of Propionyl CoA --> metabolised to odd chain fatty acids (Propionyl CoA
carboxylase)

14. Increase in Ketogenesis during Type-1 DM:

a. Decreased insulin promotes increased HSL
b. Increased FFA transported to Liver
a. Decreased insulin --> inactivates HMG CoA reductase
b. FFA metabolism diverted towards Ketogenesis

15. Congenital deficiency of Pyruvate Dehydrogenase:

a. Lactic acidosis
b. Neurodegeneration, death, muscle spasticity
c. X linked Dominant

16. Transformation:
a. Uptake of naked DNA from the environment --> expresses encoded proteins
b. Phenomenon not seen if experiment conducted in the presence of DNAse
c. Virulent form is capsulated
a. Strep pneumoniae
b. H influenzae
c. Neisseria
d. Bacillus
d. Differentiate with transduction (specialized vs general), conjugation, transposons

17. Transposons:
a. Mobile genetic elements
b. May end up close to a promoter/suppressor region; or into a plasmid

18. Citrate and ATP is a high energy signal, inhibits PFK1 (glycolysis) and stimulates acetyl CoA carboxylase
(fatty acid synthesis).

19. Neuraminidase deficiency:

a. Accumulation of NANA-Gal-Glc-Ceramide (sialidosis) [GM3]

20. Neimann-Pick disease:

a. Accumulation of foamy histiocytes (accumulation of sphingomyelin)
a. Hepatosplenomegaly (vs Tay Sachs)
b. Cherry red spot on macula; sphingomyelin deposition - causes blindness
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 b. Cherry red spot on macula; sphingomyelin deposition - causes blindness
c. Neurological deterioration; loss of previously acquired motor skills after a period of normal
development

21. Hurler - alpha L iduronidase deficiency, build up of heparan sulfate / dermatan sulfate
22. Tay-Sachs disease: Hexosaminidase deficiency; leads to GM2 accumulation
23. Ceramidase deficiency:
a. FARBER disease
b. AR
c. Painful and progressive joint deformity
d. Subcutaneous nodules
e. Granulomas in skin

24. Metachromatic leukodystrophy:

a. Arylsulfatase A deficiency
b. Nerve cells stain yellow-brown with cresyl violet
c. Demyelination, peripheral neuropathy + motor skill deficits

25. Impaired pyruvate decarboxylation (Pyruvate dehydrogenase) by Alcoholism - Thiamine B1 deficiency

because PDH needs TPP
a. Lactic acidosis

26. Pyruvate dehydrogenase deficiency:

a. Lactic acidosis
a. Neonatal presentation - severe disease
b. Adult form - milder
b. Condition improves with a Ketogenic diet
a. Lysine and Leucine --> Ketogenic amino acids; provide acetyl CoA instead of glycogenic
precursors
b. Wont increase blood lactate levels

27. Asparagine --> Aspartate --> OAA

28. Exopeptidases:
a. Procarboxypeptidase A/B
b. Aminopeptidase

29. Carbamoyl phosphate synthetase I

a. Mitochondrial
b. Requires N-acetyl glutamate (allosteric activator); synthesized by N-acetyl glutamate synthase
c. Urea cycle
a. Rate limiting step
b. Defects of the urea cycle are treated with protein restriction to reduce serum ammonia
levels
c. Deficiency symptoms - vomiting, lethargy, seizures

30. Carbamoyl phosphate synthetase II

a. Cytosolic
b. Glutamine needed
c. Pyrimidine biosynthesis

31. Hartnup disease

a. Intestinal and renal absorption of neutral amino acids defective
a. Urine levels of proline / hydroxyproline / arginine = normal
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 a. Urine levels of proline / hydroxyproline / arginine = normal
b. If they were also raised - suspect Fanconi syndrome
b. PCT defect
c. Decreased uptake of Tryptophan:
a. Essential amino acid
b. Precursor for:
i. Nicotinic acid (NAD)
ii. Niacin (B3)
iii. Melatonin
iv. Serotonin
d. Symptoms:
a. Neruological - ataxia
b. Pellagra like skin rashes (episodic erythematous & pruritic skin lesions)
c. Loose stools
d. Dementia / Diarrhoea / Dermatitis
e. Rx:
a. Niacin

32. Riboflavin deficiency (Vit B2):

a. Cheliosis, glossitis, keratitis, conjunctivitis, photophobia, lacrimation, marked corneal
vascularization, seborrheic dermatitis
b. Deficiency of FAD and FMN
c. Diagnosis:
a. Erythrocyte glutathione reductase
b. Urinary riboflavin excretion
d. Succinate dehydrogenase wont work
e. Acyl CoA dehydrogenase wont work either

33. Vitamin E deficiency - Tocopherol

a. ROS scavenger
b. Rare; but when present leads to neurological dysfunction (myelopathy)
a. Dorsal column and spinocerebellar tract disease
c. Hemolytic anemia
d. Fat soluble ffs

34. Glycogen storage diseases - present later in life; not in the neonatal stage
35. Debranching enzyme - deficiency leads to Coris disease (Type III glycogen storage)
a. Accumulation of limit dextrins in hepatocytes
b. No fatty infiltration

36. Galactose metabolism disorders

a. Galactokinase deficiency:
a. AR
b. Benign condition without hepatic involvement
c. Galactitol accumulates --> cataracts
i. Galactitol synthesized by action of aldose reductase

b. Classic galactosemia
a. AR; more common
b. Galactose-1-phosphate uridyl transferase
c. Failure to thrive soon after birth; galactitol accumulation:
i. Hepatomegaly [can cause cirrhosis]
ii. Metabolic acidosis - normal anion gap
iii. Aminoaciduria
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 iii. Aminoaciduria
d. Accumulation of galactitol --> cataracts; galactonic acid --> metabolised by HMP shunt

37. Beta galactosidase deficiency:

a. Accumulation of keratin sulfate
b. Lysosomal enzyme:
a. Breakdown of Lactose --> Galactose
c. Check if this has something to do with GM1 ganglioside accumulation [yes it does]
d. Short stature, normal intelligence, atlantoaxial instability, valvular heart disease

38. Vitamin A deficiency:

a. Note - Give Vitamin A for kids with measles
b. Maintains ocular conjunctiva, respiratory, urinary, pancreatic + other exocrine ducts
c. Symptoms:
a. Night blindness
b. Dry skin
c. Xerophthalmia
i. Keratoconjunctivitis
ii. Bitot spots (abnormal squamous cell proliferation)
d. Humoral and CMI impairment --> Damage to T cells and phagocytes
d. Causes:
a. Fat malabsorption (CF, Cholestatic liver disease)

39. Fructose metabolism disorders:

a. Essential Fructosuria
a. Fructokinase deficiency
b. AR
c. Benign, asymptomatic
d. Urine excretion + shunting of Fructose via Hexokinase (Fructose - 6 Phosphate)
i. Into glycolysis
e. Copper reduction + (benedicts test; reducing sugar)
f. Glucose oxidase deficiency - (only tests for glucose)

b. Hereditary fructose intolerance

a. Life threatening; Aldolase B deficiency
i. Intracellular accumulation of Fructose-1-Phosphate
ii. Depletion of phosphates; inhibit glycogenolysis + gluconeogenesis
b. Early age of presentation
c. Hypoglycemia and vomiting after fructose (sucrose) ingestion
d. Failure to thrive, hepatomegaly + jaundice, renal failure
e. Rx: Eliminate fructose from the diet

40. Glycogen stores are depleted in 12-18 hours of fasting; thereafter gluconeogenesis maintains blood
glucose levels
a. Pyruvate --> OAA --> Malate --> OAA --> PEP

41. HMP shunt:

a. Oxidative pathway:
a. G6PD
b. 6 phosphogluconate dehydrogenase
c. Generates NADPH
i. Active in the liver, adrenal cortex, gonads, adipose tissue, erythrocytes
ii. Needed for Cholesterol synthesis and Oxidative burst
iii. Fatty acid synthesis
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 iii. Fatty acid synthesis
b. Transketolase (TPP cofactor) - Shifts 2C groups between substrates --> glycolysis
c. Transaldolase: Shifts 3C groups --> glycolysis
d. Non oxidative reactions (Transketolase / Transaldolase)
a. Reversible
b. Can be used to synthesize Ribose from Fructose-6-P and Glyceraldehyde-P

42. Fluoride inhibits enolase (decreases lactate production by bacteria, reduces dental caries)
43. Pb inhibits aconitase

44. Intermediate junctions - just below tight junctions; help in adhesion

45. Gap junctions - connexin proteins

46. Vitamin C deficiency - Scurvy:

a. Required for prolyl hydroxylase, and lysyl hydroxylase (RER enzymes); impaired hydroxylation of
pro-collagen
b. Symptoms
a. Perifollicular hemorrhages too
b. Corkscrew hair
c. Subperiosteal hematomas (pain in legs etc) [children]
d. Hemearthroses, bleeding gums, loose teeth, peridontal infection
e. Impaired wound healing
c. People at risk:
a. Elderly
b. Malnourished
c. Alcoholics

47. Zinc deficiency:

a. Acrodermatitis enteropathica - vesicular/pustular lesions without central clearing
b. Infertility
c. Hair loss
d. Impaired taste, night blindness, impaired wound healing

48. Phenylketonuria:
a. Tyrosine becomes essential amino acid

49. BH4 - cofactor for many hydroxylase enzymes

a. Tyrosine, Dopa (hence melanin and catecholamines indirectly)
b. Serotonin synthesis
c. NO synthesis from arginine
d. Deficiency of dihydrobiopterin reductase:
a. Lead to malignant phenylketonuria (PKU) due to reduced BH4.
b. Tyrosine cant be converted to DOPA either; despite tyrosine supplementation
i. Neurological abnormalities (low catecholamines)
ii. Increase in prolactin secretion (no inhibition by dopamine)
c. PKU (classical) has deficiency of phenylalanine hydroxylase
i. Frank mental retardation by 1 year
ii. Excess accumulation of Phenylalanine inhibits tyrosinase (hence reduced melanin
synthesis)

50. Tyrosine hydroxylase - rate limiting step in catecholamine synthesis

51. Glutamate --> GABA (Glutamate decarboxylase)
52. B12 + Folate deficiency - homocysteine levels are raised
53. B12 deficiency - methylmalonyl Coa is raised
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 53. B12 deficiency - methylmalonyl Coa is raised

54. Liver doesn’t have the enzyme thiophorase:

a. Conversion of acetoacetate --> Acetoacetyl CoA
b. Linked to conversion of Succinyl CoA to Succinate of the TCA cycle
c. Used to convert ketone bodies to energy (acetyl CoA)
d. The net result is that the liver produces ketone bodies, but cant use them

55. Phenylketonuria may show features of albinism too

56. Lactic acidosis:
a. Increased metabolic rate (exercise and seizures)
b. Reduced perfusion:
a. Tissues - Reduced oxidative phosphorylation (anaerobic glycolysis)
b. Liver - Reduced metabolism of lactate
c. Decreased oxygen utilisation (CN poisoning)
d. Enzymatic defects (gluconeogenesis, glycogenolysis)

57. Gluconeogenesis normally provides glucose from metabolic intermediates - glycerol, lactate, alpha
Ketoacids - from protein and TG breakdown.
58. Medium-chain fatty acyl CoA dehydrogenase deficiency:
a. AR
b. Severe hypoglycemia in kids
c. Hypoketonemia
d. Symptoms manifest as glycogen reserves are depleted after 18 hours of fasting
a. Nausea
b. Confusion and lethargy
c. Vomiting
e. You don’t need CPT shuttle for short and long chain fatty acyl CoA
f. Rx: Don’t fast

59. Maple syrup urine disease

a. AR
b. Branched chain ketoacid dehydrogenase deficiency (BCKAD)
a. Like other dehydrogenases: Need TPP (Thiamine), Lipoate, CoA, FAD, NAD
i. Leucine --> neurotoxic
ii. Valine
iii. Isoleucine --> burnt caramel smell
b. 3 catalytic subunits; 4 genes
c. Amino acids are transaminated to their keto acids
d. Ketoacids accumulate because of BCKAD deficiency; this is neurotoxic
e. Symptoms:
a. Dystonia, poor feeding
b. Vomiting lethargy
c. Burnt caramel smell in urine
f. Leucine --> HMG CoA --> Acetoacetate + Acetyl CoA [Ketogenic]
g. Valine --> Propionyl CoA --> Succinyl CoA [Glucogenic]
h. Isoleucine --> Acetyl CoA + Propionyl CoA [Glucogenic + Ketogenic]

60. VLCFA (Very long chain fatty acids) (>22c)

a. Metabolism doesn’t take place by mitochondrial Beta oxidation
b. Activated by VLCF Acyl synthetase on peroxisomes
a. Initial dehydrogenation: FAD linked Acyl CoA Oxidase; No ATP produced here
b. Shortens the FA so it can be beta oxidised in the mitochondria
c. Branched chain phytanic acid metabolism
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 c. Branched chain phytanic acid metabolism
a. Product of chlorophyll metabolism
b. Alpha oxidation; peroxisomes
i. One carbon is removed; 19C FA is sent out for beta oxidation

d. Refsum disease:
a. Strict avoidance of chlorophyll in diet
b. AR
c. Deficiency of PhyH; leads to neurological damage, cerebellar injury, periphral neuropathies

e. Zelllweger syndrome:
a. Genetic defects in targeting matrix proteins to peroxisomes
b. Infants cant properly make myelin
c. Hypotonia, siezures
d. Hepatomegaly, mental retardation, death

f. X Linked adrenoleukodystrophy:
a. Impaired transport of VLCFA across peroxisome membrane

61. Pantothenic acid deficiency:

a. Rare, but observed in severely malnourished people
b. Undergoes ATP dependent phosphorylation --> CoA
a. Synthesis of FA / Cholesterol
b. Synthesis of Vit A / Vit D (sterols)
c. Synthesis of Heme

c. Deficiency of Acetyl CoA

a. Reduced TCA activity
b. Impaired OAA --> Citrate conversion
c. Symptoms:
i. GI distress, chronic diarrhoea
ii. Parasthesias and dysestheisas (burning feet syndrome)

62. Thiamine is a cofactor for:

a. Thiamine mediates the transfer of Co2 in these reactions, doesn’t occur in all other
dehydrogenases:
a. Pyruvate dehydrogenase
b. Alpha ketoglutarate dehydrogenase
c. Transketolase
d. Branched chain keto acid dehydrogenase (BCKAD)
e. Ethanol producing enzymes in bacteria

63. GLUT receptors:

GLUT-1 RBC, BBB (choroid plexus) Basal glucose transport
GLUT-2 Hepatocytes Regulation of insulin release
Renal tubules
Small intestine
Pancreatic beta cells
a. GLUT-3 Placenta and neurons

GLUT-4 Adipocytes It is the only insulin dependent glucose uptake transporter

Skeletal muscles
GLUT-5 Spermatocytes Fructose transport
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 GLUT-5 Spermatocytes Fructose transport
GIT
64. Orotic aciduria:
a. Disorder of pyrimidine metabolism
b. Clinical findings:
a. Hypochromic megaloblastic anemia
b. Neurological defects
c. Growth retardation (Severe)
c. Defective enzymes:
a. Oorate phosphoribosyl transferase
b. OMP decarboxylase
d. [Both are active domains of a single polypeptide: UMP synthase]
a. Catalyses the final conversion of orotic acid to UMP
e. Rx:
a. Uridine supplementation
i. Converted to UMP by nucleoside kinases [basically increases salvage of pyrimidines]
ii. UMP inhibitis CPS-II; hence reduces orotic aciduria
65. Differentiate orotic aciduria causes:
a. UMP synthase --> Normal Urea and NH3
a. Cytosolic enzyme
b. Ornithine transcarbamylase --> Low Urea and High NH3
a. Mitochondrial enzyme

66. Pyridoxal phosphate:

a. Transamination - AST / ALT
b. Deamination - Serine dehydratase
c. Decarboxylation - Histidine decarboxylase --> histamine + Co2
d. ALA dehydratase
e. Cystathione beta synthase
f. DOPA decarboxylase

67. Glycerol kinase:

a. Liver specific enzyme
a. Glycerol (released from TG breakdown; Hormone sensitive lipase)
b. Glycerol is converted to Glycerol-3-Phosphate
i. Pushed towards glycolysis or gluconeogenesis

68. Carrier proteins - undergo conformational change as substance is being transporter

a. Stereoselective transporters
69. Channels - just let that shit through

70. Proteins:
a. Secondary structure - H bonds
b. Tertiary structure:
a. Ionic bonds
b. Hydrophobic bonds
c. Hydrogen bonds
d. Disulfide bonds
i. Between two cysteine residues
ii. Enhances ability to withstand denaturation

71. Hyperammonemia
a. NH3 + Glutamate --> Glutamine [Glutamine synthase]
a. Hyperosmolarity and mitochondrial dysfuncton
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 a. Hyperosmolarity and mitochondrial dysfuncton
i. Damages the astrocytes
b. Depletes glutamate stores:
i. Reduced excitatory neurotransmitters
ii. Reduced neuronal energy production
c. Depletes alpha ketoglutarate:
i. NH3 is converted to glutamate using alpha ketoglutarate [glutamate dehydrogenase]

72. Glutamate dehydrogenase:

a. Converts Glutamate to NH3 to be used in the urea cycle
73. FIGLU test:
a. Test for folate deficiency
b. Histidine --> Formyliminoglutamate --> Glutamate
a. FIGlu to Glutamate conversion needs THF to function
b. Folate deficiency = Increased urinary excretion of FIGlu

74. Ketone bodies can't be used by:

a. Erythrocytes - no mitochondria
b. Liver - No thiophorase (succinyl CoA-acetoacetate CoA transferase)
a. Acetoacetate --> Acetoacetyl CoA

75. Clathrin (cytosolic protein) - mediates endocytosis

76. ALT - Catabolism of proteins in muscles leads to formation of alanine; nitrogen is pushed into urea cycle
(NH3) via multiple steps, and pyruvate is released

77. Substrate level phosphorylation

a. Generation of ATP/GTP in metabolic reactions
b. Succinyl CoA to Succinate; produces GTP
a. GTP used by PEP carboxykinase; OAA converted to PEP [gluconeogenesis]
c. ATP generated
a. ATP used by Pyruvate carboxylase; Pyruvate converted to OAA [only when Acetyl CoA
concentrations are high to prevent energy depletion]
1) Acetyl CoA inhibits the action of Pyruvate dehydrogenase
2) Acetyl CoA is an allosteric activator of Pyruvate carboxylase
i. Anapleurotic (maintains OAA for TCA)
ii. Gluconeogenesis

78. Sorbitol dehydrogenase

a. High concentrations of this enzyme in seminiferous tubules, since sperm use fructose as metabolic
fuel.
b. Low vmax in the sorbitol --> Fructose reaction direction
c. Hence at high glucose concentrations, excess sorbitol produced cannot be cleared out
a. Osmotic injury
d. Aldose reductase consumes NADPH
a. Very low affinity for glucose (high Km), hence activity increased significantly only in
diabetes.
b. Oxidative stress related damage in susceptible tissues
e. Tissues affected
a. Retina
b. Renal papilla
c. Schwann cells

79. Xyluose - end product of glucuronic acid metabolism, PPP intermediate

80. HMG CoA lyase - mitochondrial enzyme; HMG CoA --> Acetoacetate
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 80. HMG CoA lyase - mitochondrial enzyme; HMG CoA --> Acetoacetate

81. Ketonemia - occurs during sleep

82. G - protein
a. Transmembrane domain - Repeating alpha helix (Hydrophobic; Val Ala Ile Met Phe) interiorly
located, within the lipid bilayer

83. Homocystinuria:
a. Classic: Defect in cystathione beta synthetase (PLP + Serine)
b. B12 deficiency
a. Defect in methionine regeneration

84. Glycogen phosphorylase also needs PLP

85. PLP deficiency (B6)
a. Seborrheic dermatitis
b. Glossitis
c. Peripheral neuropathy

86. Gaucher's disease - intrasplenic lipid accumulation (splenomegaly)

a. Most common lysosomal storage disease
b. Glucocerebrosidase deficiency (Chr 1)
c. Symptoms
a. Osteopenia, bone pain
b. Anemia
c. Hepatosplenomegaly
d. Thrombocytopenia and bleeding
d. Gaucher cells (macrophages filled with lipid glucocerebroside); looks like wrinkled tissue paper

87. Lipoic acid: required as a cofactor in the pyruvate dehydrogenase family enzymes
a. Causes lactic acidosis or maple syrup urine disease when deficient (if you don’t know why by now
then you're stupid)

88. Saturable kinetics:

a. First order kinetics till Vmax
a. Constant fraction of drug metabolized with increase in dose
i. 50% of 10mg / 50% of 100mg
b. After Vmax, kinetics = zero order
a. Constant amount metabolized regardless of rise in dose of drug
i. 50% of 10mg / 5% of 100mg

89. Protein electrophoresis

a. Note the protein band at t = 0
b. Note the band size, + any new bands at t = 1
c. Note the band size of the previous bands

90. G-protein
a. Anchoring of the Carboxyl tail after the 7 transmembrane domains to the cell membrane -
covalently anchored fatty chain
a. Palmitoylation (on cysteine residues)
b. Prenylation
c. Myristoylation

91. Methylation steps in catecholamine metabolism

a. Norepinephrine --> Epinephrine; SAM using phenylethanolamine-N-methyl transferase
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 a. Norepinephrine --> Epinephrine; SAM using phenylethanolamine-N-methyl transferase
b. Epinephrine --> 3MT (metanephrine) ; Using COMT (catechol-o-methyltransferase)
a. Further metabolized to VMA (monoamine oxidase)

92. Type VI glycogen storage disease - liver glycogen phosphorylase deficiency

a. Hers disease
b. Hyperketosis is seen (since glycogen doesn’t ever get broken down)

93. Lesch-Nyhan syndrome

a. XR
b. Decreased activity of HGPRT; hence impaired salvage of purines:
a. Hypoxanthine --> IMP
b. Guanine --> GMP
c. Increased demand for denovo synthesis of purines; upregulation of glutamine:phosphoribosyl
amidotransferase [rate limiting]

d. Hyperuricemia + Hyperuricosuria (frost on skin under the childs diaper)

e. Allopurinol helps with renal symptoms; does nothing for neurological symptoms
f. Symptoms:
a. Mild mental retardation, involuntary movements
b. Self mutilation (lips, fingertips)

94. ADA deficiency - SCID; PNP deficiency - isolated T cell defect

95. Citrate:
a. Allosteric activator of acetyl CoA carboxylase: Fatty acid synthesis
b. Allosteric activator of Fructose-1,6-bisphosphate: Gluconeogenesis

96. Phosphoglucomutase: Links glycolysis, gluconeogenesis, galactose metabolism, glucuronate synthesis

97. Enzymes don’t reduce Gibbs free energy, they just reduce the energy required to make the transition
state. Speeds up reaction in the direction governed by sign of Gibbs free energy.

98. Pompe's disease

a. Cardiomyopathy and hypotonia

99. Increasing the concentration of the enzyme in the reaction mixture increases the Vmax proportionately.
100. Carbohydrate (disaccharides):
a. Trehalase - alpha(1 --> 1)
b. Isomaltase - alpha(1 --> 6)
c. Maltase- alpha (1 --> 4)
d. Sucrase - alpha (1 --> 2)

101. Maltase-glucoamylase (cleaves maltase, and cleaves alpha(1-->4) in dextrins

102. Arsenic poisoning [Note]:

a. Inhibits Pyruvate dehydrogenase (Lipoate)
b. Inhibits Glyceraldehyde 3 phosphate dehydrogenase
c. Inhibits F1 component of ATP synthase (vs Oligomycin on Fo)

103. Isocitrate dehydrogenase - activated by Ca+2

104. Malonyl CoA - inactivates Carnitine palmitoyl transferase - 1 (prevents newly synthesized fats from
undergoing beta oxidation)

105. Creatine - produced after methylation (SAM); from glycine and arginine
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 105. Creatine - produced after methylation (SAM); from glycine and arginine
106. Methylmalonic acidemia
a. Deficiency of methylmalonyl CoA mutase
a. Accumulation of methylmalonic acid
b. Reduced conversion to succinyl CoA
b. Clinical features:
a. Lethargy, vomiting, tachypnea
b. Anion gap metabolic acidosis, ketosis + hypoglycemia

107. FFA - causes serine phosphorylation --> insulin resistance (similar method to glucagon, TNFalpha)

108. Phosphorylase kinase - activates Glycogen phosphorylase in muscle

a. Activated by Ca+2 from muscle contraction

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