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Flashcards in Enzymes and Biochem principles Deck (142):
1

UDP-glucuronyl transferase

conjugates bilirubin by adding glucuronyl group
-mild decrease = Gilbert
-absent = Crigler-Najjar Type 1
-mutated = Crigler-Najjar Type 2

2

Rate limiting step in pyrimidine synthesis is catalyzed by which enzyme

Carbamoyl phosphate synthetase II
-converts glutamine + CO2 + ATP into carbamoyl phosphate

3

Autosomal recessive defect in UMP synthase

Orotic aciduria

FTT, developmental delay, megaloblastic anemia that doesn't respond to folate or B12
-no high ammonia
-orotic acid in urine
-tx with uridine monophosphate supplementation

4

Rxn catalyzed by UMP synthase

orotic acid --> UMP
-needed or pyrimidine synthesis

5

Disease resulting from absent HGPRT

Lesch-Nyhan
-X-linked
-excess uric acid production
-intellectual disability, hyperuricemia (orange "sand" in diaper), gout, dystonia, aggression, self-mutilation
-tx = allopurinol or febuxostat for gout

6

Rxns catalyzed by HGPRT

hypoxanthine --> IMP, guanine --> GMP
-purine salvage pathway

7

Rxn catalyzed by Adenosine deaminase

degradation of adenosine and deoxyadenosine in purine salvage pathway

8

Result of a deficiency in ADA

SCID - autosomal recessive
-due to increase in dATP which is toxic to lymphocytes

9

Rate limiting step in purine synthesis is catalyzed by which enzyme

Glutamine PRPP amidotransferase
PRPP --> IMP

10

Disease due to defect in mismatch repair

Lynch syndrome (HNPCC)

11

Disease due to defect in nonhomologous end joining

ataxia telangiectasia (also fanconi anemia)

12

Disease due to defect in nucleotide excision repair

Xeroderma pigmentosum (can't fix thymidine dimers - very sensitive to sun)

13

Function of DNA pol alpha

synthesize lagging strand and make RNA primers

14

Function of DNA pol delta

synthesize leading strand

15

Function of DNA pol gamma

synthesize mitochondrial DNA

16

Function of DNA pol beta

base excision repair

17

Hyperphagia, obesity, intellectual disability, hypogonadism, hypotonia

Prader-Willi syndrome

18

Defect in Prader-Willi syndrome

paternal gene on chromosome 15 is mutated/deleted; maternal gene is imprinted normally
POP - paternal, obesity/over eating, prader-willi

19

inappropriate laughter, seizures, ataxia, severe intellectual disability

Angelman syndrome

20

Defect in Angelman syndrome

maternal gene on chromosome 15 is mutated/deleted (paternal is imprinted)
-think "angel's miss their mom"
-MAMA = angelMan, ataxia, maternal gene, mood change (very happy/laughing)

21

Enzyme that converts glucose to G-6-P

glucokinase - liver, beta cells of pancreas
hexokinase - all other tissues

22

Rate limiting enzyme in glycolysis

phosphofructokinase-1 (PFK-1)

converts Fructose-6-phosphate to Fructose-1,6-bisphosphate

23

What substrates promote PFK-1?

AMP, Fructose-2,6-bisphosphate

24

What substrates inhibit PFK-1?

ATP, citrate

25

What are the two enzymes that control production of F-2,6-BP (either decrease or increase its production)?

PFK-2 makes Fructose-2,6-BP (induced by insulin to increase glycolysis)

Fructose bisphosphatase-2 converts F-2,6-BP back to F-6-P (induced by glucagon under fasted states in order to promote gluconeogenesis)

26

What is the most common glycolytic enzyme deficiency?

pyruvate kinase deficiency

27

What is the clinical consequence of a pyruvate kinase deficiency?

hemolytic anemia

28

What enzyme is missing in muscle cells to prevent them from doing gluconeogenesis?

glucose-6-phosphatase

gluconeogenesis occurs in liver mostly (some in kidney and intestinal epithelium)

29

What are the sources for gluconeogenesis?

odd chain fatty acids, TCA molecules, AA

30

What is the rate limiting step in gluconeogenesis?

fructose-1,6-bisphosphatase

converts fructose-1,6-bisphosphate to fructose-6-phosphate

31

What promotes and what inhibits fructose-1,6-bisphosphatase?

promotes = citrate (means high energy state)
inhibits = fructose-2,6-bisphosphate

32

What are the four irreversible enzymes of gluconeogenesis?

pyruvate carboxylase, PEP carboxykinase, fructose-1,6-bisphosphatase, glucose-6-phosphatase

33

How do epinephrine and glucagon raise blood sugar?

stimulate protein kinase A in the liver to activate glycogen phosphorylase kinase --> release glucose from glycogen

34

How does insulin increase glycogen formation?

activated glycogen synthase

35

What is the rate limiting step in glycogenesis?

Glycogen synthase - forms the alpha-1,4 glycosidic linkages

36

What enzyme is not found in muscles and is found in liver and acts to release glucose after glycogenolysis?

glucose-6-phosphatase

-reason glucose stored by muscles cell stays in that cell

37

Rate limiting enzyme in glycogenolysis

glycogen phosphorylase

38

Deficient enzyme in Von Gierke disease

Glucose-6-phosphatase

39

Deficient enzyme in Cori disease

debranching alpha-1,6-glucosidase

40

Deficient enzyme in Pompe disease

lysosomal alpha-1,4-glucosidase

41

Deficient enzyme in McArdle disease

skeletal muscle glycogen phosphorylase

42

Presents with lactic acidosis, hyperlipidemia, hyperuricemia (gout)

Von Gierke

43

Presents with cardiomegaly

Pompe disease (infantile type)

44

Presents with diaphragm weakness leading to resp. failure

Pompe disease

45

Presents with increased glycogen in liver, severe fasting hypoglycemia

Von Gierke

46

Presents with hepatosplenomegaly, hypoglycemia, hyperlipidemia (normal kidneys, lactate, uric acid)

Cori disease

47

Presents with painful muscle cramps, myoglobinuria with strenuous exercise which can lead to renal failure

McArdle disease

48

Severe hepatosplenomegaly, enlarged kidneys

Von Gierke disease

49

Tx for Von Gierke disease

frequent oral glucose and cornstarch

50

Which glycogen storage disease is most lethal?

Pompe disease, infantile type

51

Which glycogen storage disease can lead to seizures if untreated?

Von Gierke disease - due to high lactic acid

52

Possible products of pyruvate

oxaloacetate (gluconeogenesis), alanine (carries nitrogen), lactate (anaerobic glycolysis), acetyl-CoA (glycolysis)

53

Two main nitrogen transporters in the blood

alanine, glutamine

54

Major regulatory enzymes in TCA cycle

alpha-ketoglutarate dehydrogenase, citrate synthase, isocitrate dehydrogenase

55

Rate limiting step in TCA

isocitrate dehydrogenase

56

What are the mitochondrial uncouplers?

aspirin OD, 2,4-dinitrophenol, thermogenin in brown fat

57

What are the cofactors required by pyruvate dehydrogenase complex (links glycolysis to TCA cycle by converting pyruvate to acetyl-CoA)?

TLC for Nobody
-Thiamine pyrophosphate (Vit B1)
-Lipoic acid
-CoA (Vit B5, pantothenic acid)
-FAD (Vit B2, riboflavin)
-NAd (Vit B3, niacin)

58

What toxin causes GI distress + garlic breath and inhibits pyruvate dehydrogenase?

arsenic

59

What are the effects a deficiency in pyruvate dehydrogenase?

pyruvate gets shunted to lactate and alanine
-lactate acidosis, neuro defects, increase serum alanine
-tx = increase fat in diet, supplement with lycine and leucine to be used for energy instead of glucose
-can be X-linked, due to arsenic, or Vit B def.

60

Rate limiting enzyme in Pentose Phosphate Pathway

Glucose-6-phosphate dehydrogenase

converts G-6-P to Ribulose-5-P and NADPH
*important for forming NADPH

61

Purpose of PPP/HMP shunt

form NADPH for reductive reactions

62

How does G6PD deficiency presents?

hemolytic anemia - RBCs are unable to reduce oxidative species due to decrease in NADPH

-usually sets in after stressing factor = infection, fava beans, TB drugs, sulfonamides, nitrofurantoin

63

What are the two distinct cell types seen in hemolytic anemia with G6PD def?

bite cells, heinz bodies (denatured Hb precipitates within cells)

64

Presents with failure to thrive, jaundice, hepatomegaly, infantile cataracts, intellectual disability

Classic galactosemia

tx - exclude galactose, lactose from diet

65

Deficiency in classic galactosemia

galactose-1-phosphate uridyltransferase

66

Presents with galactosemia and galactosuria, infantile cataracts

Galactokinase deficiency

67

Presents with hypoglycemia, jaundice, cirrhosis, vomiting, urine dipstick is negative for sugar

Fructose intolerance - severe hypoglycemia because the Fructose-1-P accumulates and there is no phosphate for glycogenolysis or gluconeogenesis

Tx - decrease intake of fructose and sucrose
*dipstick cannot pick up fructose

68

What is the deficiency in fructose intolerance?

aldolase B

-aldolase B means this is the bad fructose dz

69

What is the deficiency in essential fructosuria?

fructokinase

-kinase is the kind disease

70

Benign dz that presents with fructose in blood and urine

Essential fructosuria

71

What disease results from protein malnutrition?

Kwashiokor

72

How does kwashiokor present?

FLAMES - fatty liver, anemia, malnutrition, edema, skin lesions (child in Africa with swollen belly)

73

What disease results from total calorie malnutrition and causes muscle wasting, loss of subcutaneous fat, and edema?

Marasmus

74

What is the rate-limiting enzyme in ketone body synthesis?

HMG CoA synthase

75

What occurs in refeeding syndrome?

cells reuptake lytes --> drop in serum mag, phosphate, potassium
-can lead to arrhythmias and neuro problems

76

What leads a fruity odor on the breath?

conversion of acetoacetate to acetate in someone who is producing ketone bodies

77

What ketone body is detected on urine test?

acetoacetate (not Beta-hydroxybutyrate)

78

What occurs in starvation and DKA to cause ketone synthesis?

depletion of oxaloacetate depleted for gluconeogenesis --> build up acetyl-CoA more than TCA cycle can handle

-results in glucose and FFA shunted to ketone synthesis

79

What occurs in alcoholism to cause ketone synthesis?

excess NADH (low NAD+) shunts oxaloacetate to malate --> build up acetyl-CoA more than TCA cycle can handle

-results in glucose and FFA shunted to ketone synthesis

80

What are the fuels used during fasting states?

glucose (glycogenolysis and gluconeogenesis), FA from fat

-glucose is used by all tissues

81

What are the fuels made/used after fasting for 24 hours?

glucose and FA produced

-brain uses glucose
-muscles/other tissues use mostly FA, some glucose

82

What are the fuels made/used after fasting for 48 hours?

glucose, FA, ketone bodies produced

-brain uses mostly glucose, some ketones
-muscles/other tissues use mostly FA, some ketones

83

What are the fuels made/used after fasting for 5 days?

glucose, FA, ketone bodies produced

-brain uses mainly ketone bodies
-muscles/other tissues mainly use FA, some ketones

after 3 days, 60% of energy comes from ketones

84

Apolipoprotein that activates LCAT

ApoA-I

85

Apolipoprotein that mediates chylomicron secretion

ApoB-48

86

Apolipoprotein that mediates VLDL secretion and allows particles to leave the liver

ApoB-100

87

Apolipoprotein that mediates remnant particle uptake

ApoE

88

Apolipoprotein that acts as a cofactor for lipoprotein lipase

ApoC-II

89

Autosomal recessive mutation in MTP gene, presents with decrease ApoB-48 and ApoB-100, steatorrhea, night blindness and ataxia (due to decrease uptake of fat soluble vitamins)

Abetalipoproteinemia

90

Key cells seen on a peripheral smear of a pt with abetalipoproteinemia

acanthocytosis of RBCs (defect in cell membrane)

91

Functions to deliver dietary TGs to peripheral tissues and delivers cholesterol back to liver

chylomicron

92

Functions to deliver hepatic TGs to peripheral tissues

VLDL

93

Degradation product of VLDL, delivers TGs and cholesterol to liver

IDL

94

Delivers hepatic cholesterol to peripheral tissues, take up via receptor-mediated endocytosis

LDL

95

Deficiency in familial hypercholesterolemia

LDL receptor deficiency

96

Mediates reverse cholesterol transport from periphery to liver, repository for ApoC and ApoE

HDL

97

Presents with pancreatitis, hepatosplenomegaly, pruritic xanthomas, but no increased risk for arthersclerosis

high TGs, chylomicrons, cholesterol

Type I Hyperchylomicronemia

98

Defect in Type I hyperchylomicronemia

lipoprotein lipase or apolipoprotein C-II deficiency

99

Defect in Type IIa Familial hypercholesterolemia

absent or defective LDL receptors

100

Presents with high LDL cholesterol, can present with an MI in a very young person (before 20), tendon xanthomas (achilles typically), increased risk or atherosclerosis

Familial hypercholesterolemia

101

Presents with high TGs (>1000), acute pancreatitis

Hypertrigyceridemia - hepatic overproduction of VLDL

102

Rate limiting enzyme for fatty acid synthesis

Acetyl-CoA carboxylase (occurs in cytoplasm)

103

Rate limiting enzyme for Beta-oxidation of fatty acids

carnitine acetyltransferase I (occurs in mitochondria)

104

Rate limiting enzyme for cholesterol synthesis

HMG CoA reductase

105

What compounds can be made from phenylalanine?

tyrosine, dopa, dopamine, NE, Epi

106

What is the precursor to melanin?

dopa

107

What enzyme converts dopamine to NE and what cofactor does it need?

dopa beta-hydroxylase

cofactor = Vit C

108

What cofactor helps convert NE to Epi?

SAM (also uses cortisol)

109

What compounds can be made from arginine?

creatine, urea, nitric oxide

110

What compounds can be made from glutamate?

GABA (requires B6), Glutathione

111

What compounds can be made from glycine?

porphyrin (need B6) --> heme

112

What compounds can be made from histadine?

histamine (need B6)

113

What compounds can be made from tryptophan?

niacin (requires B6, B2) --> NAD/NADP
serotonin (requires BH4, B6) --> melatonin

114

Essential Amino Acids

PVT TIM HaLL - phenylalanine, valine, tryptophan, threonine, isoleucine, methionine, histadine, lysine, leucine

115

Acidic Amino Acids

Aspartate, Glutamate (negative charge at body pH)

116

Basic Amino Acids

Arginine, Lysine, Histadine

117

Amino acids that are present in histones

lysine, arginine

118

Amino acids needed during growth

arginine, histadine

119

Rate limiting enzyme in urea cycle

carbamoyl phosphate synthetase I

-converts CO2 + NH3 (ammonia) to carbmoyl phosphate
-found in mitochondria

120

Presents with increased orotic acid in urine and blood, decreased BUN, symptoms of hyperammonemia, presents in first few days of life

Ornithine transcarbamylase deficiency

-normally converts ornithine --> citrulline for elimination of ammonia
-tx = limit protein in diet

121

Tremor, slurring speech, somnolence/lethargy, vomiting, cerebral edema, blurring vision

hyperammonia - due to defect in urea cycle or liver disease

122

Presents with dermatitis, dementia, and diarrhea but not due to deficient Vit B3

Hartnup disease

123

Deficiency in Hartnup disease

deficiency in neutral amino acid transporters in the proximal tubule and on enterocytes --> decrease tryptophan for conversion to niacin --> pellegra results

124

Presents with vomiting, poor feeding, urine smells sweet; can lead to CNS defects, intellectual disability, death

Maple syrup urine disease

125

Deficiency in maple syrup urine disease

decreased branched-chain alpha-ketoacid dehydrogenase --> blocked degradation of branched amino acids (leucine, isoleucine, valine)

-tx = restrict branched chain amino acids

126

Presents with intellectual disability, growth retardation, seizures, fair skin, eczema, and musty body odor if untreated

Phenylketonuria (PKU)

127

Deficiency in PKU

decrease in phenylalanine hydroxylase or decrease in BH4 (tetrahydrobiopterin) --> can't make tyrosine from phenylalanine

-tx with decrease phenylalanine (aspartate, meat, dairy), increase tyrosine
-causes build up phenylketones --> in urine

128

Presents with recurrent cystine hexagonal kidney stones

Cystinuria

129

Defect in cystinuria

defect in renal PCT and interstitial AA transporter that prevents reabsorption of COLA - cysteine, ornithine, lysine, arginine

tx = acetazolamide to alkalinize the urine

130

Presents with increased homocysteine in the urine, intellectual disability, osteoporosis, marfanoid habitus, kyphosis, lens subluxation (downward and inward), thrombosis, atherosclerosis

Homocystinuria

131

Defect in homocystinuria

Cystathionine synthase deficiency, or
decreased affinity of cystathionine synthase for pyridoxal phosphate (B6), or methionine synthase

Tx = pyridoxine (Vit B6) supplements or decrease methionine intake

132

Presents with bluish-black connective tissue (skin) and sclera (onchronosis), urine turns black on prolonged exposure to air, arthalgias

Alkaptonuria

133

Defect in alkaptonuria

deficiency in homogentisate oxidase --> can't break down tyrosine --> homogentistic acid builds up in tissues

benign

134

Defect in albinism

decreased tyrosinase activity or defected tyrosine transport --> can't make melanin

135

Cherry red spot on macula, lysosomes with onion skin, progressive neurodegeneration

Tay-Sachs disease

deficiency in hexosaminidase A - accumulate GM2 ganglioside

136

Peripheral neuropathy, developmental delay, optic atrophy, globoid cells

Krabbe disease

deficiency of galactocerebrosidase - build up galactocerebrosidase

137

Central and peripheral demyelination, with ataxia and dementia, vision loss

Metachromatic leukodystrophy

deficiency of arylsulfatase A - cerebroside sulfate

138

Progressive neurodegeneration (dysphagia, dysarthria, ataxia), hepatosplenomegaly, foam cells, cherry spot on macula

Niemann-Pick disaese

deficiency of sphingomyelinase- build up sphingomyelin

139

Hepatosplenomegaly, pancytopenia, osteoporosis, lipid-laden macrophages that resemble crumpled tissue paper

Gaucher disease

deficiency in glucocerebrosidase - build up glucocerebroside

140

Triad of episodic peripheral neuropathy, angiokeratomas (little papules around buttock/groin), hypohidrosis

-later leads to renal failure and CV dz

Fabry disease (X-linked)

alpha-galactosidase A - build up ceramide trihexoside

141

Developmental delay, gargoylism (course facial features and short statures), corneal clouding, hepatosplenomegaly

Hurler syndrome

alpha-L-iduronidase deficiency

142

Mild Hurler syndrome + aggressive behavior, without corneal clouding

Hunter syndrome (X-linked)

iduronate sulfatase