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Flashcards in Biochem - all pathways Deck (113)
1

Pompe Disease

signs?

enzyme defect?

severe cardiomeagly, hepatomeagly, macroglossia, hypotonia, mental retardation, glycogen accumulation in lysosomes

∆ alpha-glucosidase/acid maltase - converts branched glycogen -> glucose in lysosomes

2

McArdle Disease

signs?

enzyme defect?

increased muscle glycogen
sx occurs w/ exercise
- weakness + fatigue, little to no rise in blood lactate
- myoglobinuria
- arrhythmias + electrolyte ∆s

∆ glycogen phosphorylase - converts branched glycogen -> limit dextrans

3

Cori Disease

signs?

enzyme defect?

accumulation of small chain dextrin-like material in cytosol
hypoglycemia
hyperTg
ketoacidosis
hepatomeagly
(basically a milder version of Von-Gierke but with normal lactate levels)

∆ debranching enzyme - converts limit dextrans -> glycogen

4

RA: ∆ alpha-glucosidase/acid maltase

Pompe Disease

converts branched glycogen -> glucose in lysosomes

5

RA = ∆ glycogen phosphorylase

McArdle Disease

converts branched glycogen -> limit dextrans

6

RA = ∆ debranching enzyme

Cori disease

converts limit dextrans -> glycogen

7

Mild Galactosemia

signs?

enzyme defect?

galactosuria
cataracts (due to galacticol accumulation) - failure to tract objets, ø social smile
no hepatomeagly

∆ galactokinase - converts galactose -> galactose-1-P

8

Severe Galactosemia

signs?

enzyme defect?

trmt?

failure to thrive
intellectual disability
cataracts
hepatomeagly (due to PO4 depletion, therefore no gluconeogenesis, no glycogenolysis)

∆ G1P uridyltransferase - converts galactose-1-P -> glucose-1-P

Trmt: exclude galactose + lactose

9

RA = ∆ galactokinase

Mild Galactosemia

converts galactose -> galactose-1-P

10

RA = ∆ G1P uridyltransferase

Severe Galactosemia

converts galactose-1-P -> glucose-1-P

11

RA = trmt: exclude galactose + lactose

Severe Galactosemia

12

Cataracts, retinopathy, and peripheral neuropathy in a patient w/ poorly controlled diabetes should make you think of....

sorbitol accumulation in schwann cells, retina, and kidneys due to ∆ sorbitol dehydrogenase (converts sorbitol -> fructose)

13

Von Gierke

signs?

enzyme defect?

trmt?

severe fasting hypoglycemia
hepatomeagly (due to increased glycogen in liver)
increased blood lactate (more gets funneled down)

∆ Glucose-6-phosphatase - converts glucose-6-P -> Glucose

trmt: frequent oral glucose + starch; avoid fructose and galactose

14

RA = ∆ sorbitol dehydrogenase

sorbitol accumulation sorbitol accumulation in schwann cells, retina, and kidneys

converts sorbitol -> fructose

15

RA = ∆ Glucose-6-phosphatase

Von Gierke

converts glucose-6-P -> Glucose

16

RA = trmt: frequent oral glucose + starch; avoid fructose and galactose

Von Gierke

17

Hemolytic Anemia in PPP

signs?

enzyme defect?

hemolytic anemia w/ exposures to oxidative stress (due to øNADPH)
- sulfa Rx
- antimalarials
- infection/free radicals
- fava beans
- anti-TB Rx

∆ G6P DH - converts glucose-6-P to 6-phosphogluconate

18

Essential Fructosuria

signs?

enzyme defect?

Fructosemia + fructosuria (reducing agent in urine)

∆ fructokinase - converts fructose -> fructose-1-P

19

Fructose Intolerance

signs?

enzyme defect?

Fructosuria
decreased glycogenolysis + gluconeogenesis (due to decr. P)
sx that occur after consuming fruit juice/honey:
- hypoglycemia
- jaundice
- cirrhosis
- vomiting

∆ Aldolase B - converts fructose-1-P to glyceraldehyde

20

Hemolytic Anemia in Glycolytic Pathway

signs?

enzyme defect?

hemolytic anemia (due to ø glycolysis and ø ATP to maintain RBC structure)

∆ pyruvate kinase - converts PEP -> Pyruvate

21

RA: ∆ G6P DH

Hemolytic anemia due to PPP

converts glucose-6-P to 6-phosphogluconate

22

RA: ∆ Fructokinase

Essential Fructosuria

converts fructose -> fructose-1-P

23

RA: ∆ Aldolase B

Fructose Intolerance

converts fructose-1-P to glyceraldehyde

24

RA: ∆ pyruvate kinase

hemolytic anemia in glycolytic pathway

converts PEP -> Pyruvate

25

∆ pyruvate carboxylase

downregulation of Citric acid cycle/energy producing capacity of the cell

converts Pyruvate -> oxaloacetate

26

∆ pyruvate dehydrogenase

signs?

trmt?

Lactic acidosis
increase serum alanine
neurological defects

trmt: increase fat, lysine, leucine

converts pyruvate -> Acetyl CoA

27

arsenic blocks these two enzymes

net ATP?

pyruvate DH
alpha-ketoglutarate DH

net: 0 ATP

28

Symptoms due to defects in carnitine shuttle

hypoketoic
hypoglycemia
hyptonia (weakness)

29

∆ Acyl-CoA DH

low fasting glucose

30

Maple Syrup Disease

signs?

enzyme defect?

trmt?

CNS defects (retardation)
urine that smells like burnt sugar/maple syrup

∆ alpha-keto acid dehydrogenase - converts branched chain a.a. to propionyl CoA

trmt: decrease isoleucine, leucine, valine, increase thiamine (B1)

31

Folic acid deficiency

Macrocytic anemia
hypersegmented PMN
Increased homocysteine

32

Cobalamin deficiency

Macrocytic anemia
hypersegmented PMN
DCML problems
Increased homocysteine + methylmalonyl CoA

33

Homocystinuria

signs?

enzyme defect?

trmt?

downward + inward lens displacement
kyphosis
osteoporosis
stroke, MI
intellectual disability

∆ homocysteine methyltransferase - 2 reactions:
homocystine -> methionine
methylmalonyl CoA -> succinyl CoA

trmt: pyridoxine

34

RA: ∆ alpha-keto acid dehydrogenase

Maple Syrup Disease

converts branched chain a.a. to propionyl CoA

35

RA: ∆ homocysteine methyltransferase

homocystinuria

homocystine -> methionine
methylmalonyl CoA -> succinyl CoA

36

Ornithine transcarbamylase deficiency

signs?

enzyme defect?

trmt?

increased orotic acid
hyperammonemia
ø megaloblastic anemia
decreased BUN

trmt: restrict proteins

∆ = Ornithine transcarbamylase (OTC) - converts urea cycle intermediates -> carbomoyl phosphate

37

Orotic Aciduria

signs?

enzyme defect?

trmt?

needle-shaped orotic acid crystals
ø hyperammonemia
megaloblastic anemia (hypochromic)
hypersegmented nuclei


∆ UMPS (orotidine phosphorribosyl Transferase and Orotidine-5-phosphate decarboxylase) - converts orotic acid -> UMP

trmt: uridine

38

Hyperammonemia + increased ornithine

∆ N-acetyl glutamate - cofactor of carbamoyl phosphate synthetase (CPSI), which converts NH3 + CO2 -> carbomoyl phosphate

39

RA: ∆ Ornithine transcarbamylase (OTC)

Ornithine transcarbamylase deficiency

converts urea cycle intermediates -> carbomoyl phosphate

40

RA: ∆ orotidine phosphorribosyl transferase

Orotic Aciduria - part of UMPS complex with orotidine-5-phosphate decarboxylase

converts orotic acid -> UMP

41

RA: ∆ orotidine-5-phosphate decarboxylase

Orotic Aciduria - part of UMPS complex with orotidine phosphorribosyl transferase

converts orotic acid -> UMP

42

difference between CPS I and CPS II?

how do you tell if one is deficient over the other?

CPS I - converts NH3 + CO2 to carbomyl phosphate; requires N-acetylglutamate

CPS II - converts glutamine + CO2 to carbomyl phosphate

w/ CPSI deficiency, you get increased ornithine

43

Lesch-Nyhan

signs?

enzyme defect?

trmt?

self-mutilating behavior
excess uric acid

trmt: allopurinol, febuxostat

∆ HGPRT - converts guanine/hypoxanthine -> GMP, IMP

44

SCID

signs?

enzyme defect?

excess ATP
decreased lymphocytes
decreased DNA synthesis

∆ ADA - converts AMP -> guanine/hypoxanthine

45

RA: ∆ HGPRT

Lesch-Nyhan

converts guanine/hypoxanthine -> GMP, IMP

46

RA: ∆ ADA

SCID

converts AMP -> guanine/hypoxanthine

47

RA: trmt: allopurinol, febuxostat

Lesch-Nyhan

48

PKU

signs?

enzyme defect?

trmt?

ø melanin, pale fair skinned
musty body odor
eczema
seizures, intellectual disability
growth retardation
increased phenylketones in urine (phenyl-acetate, -lactate, -pyruvate)
tyrosine becomes an essential a.a.

∆ phenylalanine hydroxylase - converts phenylalanine -> tyrosine

trmt: decrease phenyalanine, increase tyrosine, avoid aspartame

49

Albinism

ø melanin, pale fair skinned

∆ tyrosinase - converts DOPA -> melanin

50

Alkaptonuria

signs?

enzyme defect?

urine turns dark @ room air
brown connective tissue + sclera
arthralgia

∆ Homogenistic acid oxidase - converts Homogenistic acid -> maleyacetoacetic acid

51

RA: ∆ phenylalanine hydroxylase

PKU

52

RA: ∆ tyrosinase

Albinism

53

RA: ∆ Homogenistic acid oxidase

Alkaptonuria

54

Sideroblastic anemia

∆ ALAS or B6 (losses inducible by isoniazid)

(no B6 -> peripheral neuropathy, convulsions, irritability)

55

lead inhibits these two enzymes

ALAD, Ferrochetolase

56

Acute intermittent porphyria

signs?

enzyme defect?

trmt?

painful abdomen
port-wine colored urine
polyneuropathy (muscle weakness)
psychological ∆s

trmt: glucose + heme (feeds-back to inhibit ALAS)

∆ Porphobilinogen deaminase - converts porphobilinogen -> Hydroxymethylbilane

57

Porphyria cutanea tarda

signs?

enzyme defect?

blistering cutaneous photosensitivity

∆ Uroporphyrinogen decarboxylase - converts Uroporphyrinogen III -> Coproporphyrinogen III

58

RA: ∆ porphobilinogen deaminase

converts porphobilinogen -> Hydroxymethylbilane

59

RA: ∆ Uroporphyrinogen decarboxylase

converts Uroporphyrinogen III -> Coproporphyrinogen III

60

RA: trmt: glucose + heme

Acute intermittent porphyria

61

Crigler-Najjar Syndrome

signs?

enzyme defect?

trmt?

jaundice
kernicterus (bilirubin deposition in brain)
increased unconj. bilirubin.

trmt: plasmapheresis and phototherapy

∆ UDP-glucuronosyltransferase - converts bilirubin -> bilirubin diglucuronide, water soluble

62

Gilbert syndrome

signs?

enzyme defect?

symptomatic or mild jaundice
elevated unconj. bilirubin w/o overt hemolysis
bilirubin increases w/ fasting and stress.

low UDP-glucuronosyltransferase - converts bilirubin -> bilirubin diglucuronide, water soluble

63

Dubin- Johnson syndrome

signs?

enzyme defect?

Conjugated hyperbilirubinemia
black liver

defective liver excretion-> obstructive jaundice

64

Rotor syndrome

signs?

enzyme defect?

mild conjugated hyperbilirubinemia
ø black liver

decreased liver excretion-> obstructive jaundice, milder version of DJ syndrome

65

RA: ∆ UDP-glucuronosyltransferase

Crigler-Najjar

converts bilirubin -> bilirubin diglucuronide, water soluble

66

RA: low UDP-glucuronosyltransferase

Gilbert syndrome

converts bilirubin -> bilirubin diglucuronide, water soluble

67

RA: defective liver excretion-> obstructive jaundice

Dubin Johnson syndrome

68

RA: decreased liver excretion-> obstructive jaundice

Rotor syndrome

69

derivative of NO

argnine

70

derivatives of urea

arginine + aspartate

71

derivatives of heme

glycine + succinyl CoA

72

derivatives of creatinine

glycine + arginine + SAM

73

derivatives of GABA

glutamate

74

derivatives of glutathione

glutamate

75

derivatives of pyrimidines

glutamate + aspartate

76

derivatives of purines

glutamate + aspartate + glycine

77

derivatives of histamine

histidine

78

derivatives of dopamine

phenylalanine

79

derivatives of melatonin

tryptophan

80

derivatives of niacin

tryptophan

81

derivatives of thyroxine, melanin

tyrosine

82

Net ATP from aerobic respiration in the heart + liver
Net ATP from aerobic respiration in the muscle

Net ATP from anaerobic respiration

Net ATP from arsenic poisioning

32 = heart + liver
30 = muscle

anaerobic = 2

arsenic = 0

83

glucokinase is present in what tissues? hexokinase?

glucokinase = liver, ß cells of pancreas
hexokinase = all other tissues

84

Which gene is associated with maturity-onset diabetes of the young?

Glucokinase

85

How do these affect oxidative phosphorylation?

Rotenone, cyanide, antimycin A, CO

all inhibit electron transport, resulting in a DECREASED proton gradient and no ATP synthesis

"DRACCO"

86

How does oligomycin affect oxidative phosphorylation?

inhibits ATP synthase, resulting in INCREASED proton gradient and no ATP synthesis

87

How does 2,4-DNP, aspirin, and thermogenin affect oxidative phosphorylation?

increases permeability of the membrane, resulting in decreased proton gradient and increased O2 consumption

ATP synthesis stops, but e-transport continues, resulting in heat production

88

essential a.a

isoleucine, phenylalanine, threonine, tryptophan
lysine, leucine
methionine, histidine, valine

"PITT LYed to LUCy about going to the MET w. HIS ex VALerie

89

a.a. in histones

arginine and lysine

90

acidic a.a.

glutamic acid
aspartic acid

"GLUe is esp (ASP) acidic"

91

basic a.a.

Histidine
Lysine
Arginine

"HIS LYes ARe basic"

92

purpose of Cori cycle?

What drug can inhibit this cycle and what happens?

transports lactate to the liver for gluconeogenesis to prevent lactic acidosis in muscles

pathway can be inhibited by METFORMIN, resulting in lactic acidosis in patients with renal failure since the kidneys can't handle excess lactic acid

93

purpose of alanine cycle?

shuttles alanine to the liver to make more glucose and to prevent NH3 buildup in muscles

94

pathophysiology of hepatic encephalopathy?

sx?

trmt?

liver dz (cirrhosis) or urea cycle enzyme deficiencies can result in an excess of NH4, which depletes a-KG, leading to an inhibition of TCA

sx: tremor (asterixis), slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision

Trmt: limit protein, Benzoate or phenylbutryate (bind a.a. and lead to its excretion) or Lactulose (acidifies GI to trap NH4 for excretion)

95

∆ N-acetylglutamate

required cofactor for CPS I (carbamoyl phosphate synthetase I)

leads to HYPERAMMONEMIA

increased ornithine (compare to a pure CPSI deficiency)

96

serotonin is derived from which a.a.?

tryptophan

97

niacin is derived from which a.a.?

tryptophan

98

melatonin is derived from which a.a.?

tryptophan

99

histamine is derived from which a.a.?

histidine

100

heme is derived from which a.a.?

glycine

101

porphyrin is derived from which a.a.?

glycine

102

GABA is derived from which a.a.?

glutamate

103

glutathione is derived from which a.a.?

glutamate

104

creatinine is derived from which a.a.?

argninine

105

urea is derived from which a.a.?

argninine

106

NO is derived from which a.a.?

argninine

107

DOPA and dopamine is derived from which a.a.?

phenyalanine (-->tyrosine)

108

melanin is derived from which a.a.?

phenyalanine (-->tyrosine)

109

NE is derived from which a.a.?

phenyalanine (-->tyrosine)

110

Epi is derived from which a.a.?

phenyalanine (-->tyrosine)

111

RA: trmt for PKU

decrease phenyalanine
increase tyrosine
avoid aspartame

112

Cystinuria

enzyme defect?

signs?

diagnostic test

trmt?

∆ PCT + intestinal a.a. transporter for cysteine, ornithine, lysine, and arginine - COLA

hexagonal cystine stones

urinary cyanide-nitroprusside test

trmt: alkalinization (K-citrate or acetazolamide) and chelating agents

113

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