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Flashcards in more metabolism Deck (111):
1

what form of AAs are found in proteins?

L-form

2

essential AAs

must come from diet.

Glucogenic: Val, Met, His, Arg.
Ketogenic: Lys, Leu.
Both: Ile, Phe, Thr, Trp, Tyr

3

acidic AAs

Asp and Glu - neg charge at body pH

4

basic AAs

His, Lys, Arg.

Arg is most basic.
His has no charge at body pH.

5

which AAs are required during periods of growth?

His, Arg

6

which AAs are increased in histones?

Arg, Lys - bind neg charged DNA

7

AA catabolism yields?

common metabolites (pyruvate, acetyl CoA) that are used as fuel.

excess nitrogen (NH4+) that must be excreted.

8

how is excess NH4+ from AA catabolism excreted?

converted to UREA,
excreted by kidneys

9

contributors to urea structure

1. NH4+
2. CO2
3. aspartate

10

urea cycle intermediates (in order)

Ornithine.
Carbamoyl phosphate.
Citrulline.
Aspartate.
Argininosuccinate.
Fumarate.
Arginine.
Urea.

"Ordinarily Careless Crappers Are Also Frivolous About Urination"

11

hyperammonemia

results in excess NH4+
which depletes alpha-KG
leading to inhib of TCA cycle.

12

causes of hyperammonemia

acquired: liver disease.

hereditary: urea cycle enz def.

13

ammonium intoxication

tremor.
slurred speech.
somnolence.
vomiting.
cerebral edema.
blurred vision.

14

TX of hyperammonemia

1. limit protein in diet.

2. benzoate or phenylbutyrate: bind AA for excretion (bypass urea cycle), thus decreasing ammonia levels.

3. lactulose: acidify GI lumen and trap NH4+ for excretion.

15

ornithine transcarbamoylase deficiency

most common urea cycle d/o.
only X-linked recessive one.

interfere w/ability to eliminate ammonia.

16

presentation of OTC def

often evident in first few days of life but may present with late onset.

severe neuro problems.
sx of hyperammonemia.
OROTIC ACID in bld and urine.
decreased BUN (urea).

17

what happens to excess carbamoyl phosphate in OTC def?

converted to OROTIC ACID of pyrimidine synth pathway

18

catecholamine cofactors

dopa to dopamine: B6.
dopamine to NE: vit C.
NE to epi: SAM.

19

catecholamine breakdown products

via MAO and COMT.

dopamine: HVA.
NE: VMA.
epi: metanephrine.

20

phenylketonuria (PKU)

due to decreased phenylalanine hydroxylase.

auto recessive. 1:10000.

21

malignant PKU

due to decreased tetrahydrobiopterin (THB) cofactor

22

what AA becomes essential in PKU?

tyrosine

23

findings in PKU

mental retardation.
growth retardation.
seizures.
fair skin.
eczema.
musty body odor.

increased phenylalanine = excess phenylketones in urine.

24

what creates musty body odor in PKU?

disorder of aromatic amino acid metabolism

25

phenylketones

phenylacetate.
phenyllactate.
phenylpyruvate.

26

PKU in newborns

screened for 2-3 days after birth
(normal at birth due to maternal enzyme during fetal life)

27

TX of PKU

dietary restrictions:
1. decrease phenylalanine (in aspartame).
2. increase tyrosine.

28

maternal PKU

lack of proper dietary therapy during pregnancy.

findings in infant:
microcephaly.
mental retardation.
growth retardation.
congenital heart defects.

29

alkaptonuria (ochronosis)

congenital deficiency of homogentisic acid oxidase - part of tyrosine degradation to fumarate.

auto recessive.
benign.

30

findings in alkaptonuria (ochronosis)

dark conn tissue.
brown pigmented sclera.
urine turns BLACK on prolonged exposure to air.

31

how does homogentisic acid affect cartilage?

toxic to it- cause debilitating arthralgias

32

albinism

congenital deficiency of:
1. tyrosinase: needed to synthesize melanin from tyrosine. auto recessive.

2. defective tyrosine transporters: decreased tyrosine = decreased melanin.

33

melanocytes in albinism

usually NORMAL in number and location, though possible cause of albinism is lack of migration of neural crest cells

34

variable inheritance of albinism due to?

locus heterogeneity
(vs. X-linked recessive ocular albinism)

35

features of albinism

white hair.
blue eyes.
pink/white skin.
increased risk of skin cancer.

36

homocystinuria

3 auto recessive forms.
result in EXCESS HOMOCYSTEINE.

37

what AA becomes essential in homocystinuria?

cysteine

38

findings in homocystinuria

increased homocysteine in urine.
mental retardation.
osteoporosis.
tall stature.
kyphosis.
lens subluxation (down and in).
atherosclerosis- stroke, MI**

39

homocystinuria causes

1. cystathionine synthase def.

2. decreased affinity of cystathionine synthase for pyridoxal phosphate.

3. homocysteine methyltransferase def.

40

TX of cystathionine synthase def

decrease methionine.
increase cysteine, B12, folate in diet.

41

TX of decreased affinity of cystathionine synthase for pyridoxal phosphate

greatly increase vit B6 in diet

42

TX of homocysteine methyltransferase def

B12 supp (enz requires B12)

43

cystinuria

hereditary defect of renal tubular AA transporter for cysteine, ornithine, lysine, and arginine in PCT of kidneys.

auto recessive.

44

cystine

2 cysteines connected by disulfide bond

45

excess cystine in urine leads to?

cystine kidney stones (hexagonal crystals)- form staghorn calculi

46

cystinuria TX

acetazolamide: alkalinize urine

47

maple syrup urine disease

blocked degrad of branched amino acids (Ile, Leu, Val) due to decreased alpha-ketoacid dehydrogenase

"I Love Vermont MAPLE SYRUP from maple tree BRANCHES"

48

what is increased in blood in maple syrup urine disease?

alpha-ketoacids, esp Leu

49

findings in maple syrup urine disease

urine smells like MAPLE SYRUP.
severe CNS defects.
MR.
dystonia.
poor feeding.
death.

50

Hartnup disease

auto recessive defect of neutral amino acid transporters on renal and intestinal epith cells

51

findings in Hartnup disease

tryptophan excreted in urine.
decreased absorp from gut.

PELLAGRA:
Diarrhea,
Dermatitis,
Dementia.

52

glycogen branches

alpha 1,6 bonds

53

glycogen linkages

alpha 1, 4 bonds

54

glycogen in skel muscle

glycogenolysis: glycogen to G1P to G6P (cannot make glucose).

G6P rapidly metabolized during exercise.

55

glycogen in hepatocytes

stored in liver.
undergoes glycogenolysis to maintain blood sugar at appropriate levels.

56

enzymes in glycogen synth

1. UDP-gluc pyrophosphorylase.
2. glycogen synthase.
3. branching enzyme.

57

enzymes in glycogenolysis

1. glycogen phosphorylase.
2. debranching enzyme.

58

alpha-1,4-glucosidase

degrades a small amount of glycogen in lysosomes

59

glycogen storage diseases

12 types total.
abn glycogen metabolism.
accum of glycogen in cells.

"Very Poor Carbohydrate Metabolism"
Von Gierke's.
Pompe's.
Cori's.
McArdle's.

60

Von Gierke's disease (type I)

glycogen storage disease.
deficient GLUCOSE-6-PHOSPHATASE.

61

findings in Von Gierke's

severe fasting hypoglycemia.
great increase in liver glycogen.
increase blood lactate.
hepatomegaly.

62

Pompe's disease (type II)

glycogen storage disease.
deficient LYSOSOMAL ALPHA-1,4-GLUCOSIDASE (ACID MALTASE).

63

findings in Pompe's

cardiomegaly.
systemic findings- liver, muscle.
early death.

"Pompe's trashes the pump (heart)"

64

Cori's disease (type III)

glycogen storage disease.
milder form of type I with NORMAL blood lactate levels.

deficient DEBRANCHING ENZ (ALPHA-1,6-GLUCOSIDASE).

65

McArdle's disease (type V)

glycogen storage disease.
defecient SKELETAL MUSCLE GLYCOGEN PHOSPHORYLASE.

66

findings in McArdle's

increased glycogen in muscle but cannot break it down....

painful muscle cramps, myoglobinuria with strenuous exercise.

67

Fabry's disease

LSD: sphingolipidosis.
XR inheritance.
deficient alpha-galactosidase A.

accumulate: ceramide trihexoside.

68

findings in Fabry's

peripheral neuropathy of hands, feet.
angiokeratomas.
cardiovascular.
renal.

69

Gaucher's disease

LSD: sphingolipidosis.
AR inheritance.
deficient glucocerebrosidase.
most common LSD.

accumulate: glucocerebroside.

70

findings in Gaucher's

hepatosplenomegaly.
aseptic necrosis of femur.
bone crises.
pancytopenia.

GAUCHER'S CELLS: macrophages that look like crumpled tissue paper.

71

Niemann-Pick disease

LSD: sphingolipidosis.
AR inheritance.
deficient sphingomyelinase.

accumulate: sphingomyelin.

72

findings in Niemann-Pick

progressive neurodegeneration.
hepatosplenomegaly.
cherry-red spot on macula.
FOAM CELLS.

73

Tay-Sach's disease

LSD: sphingolipidosis.
AR inheritance.
deficient hexosaminidase A.

accumulate: GM2 ganglioside.

74

findings in Tay-Sach's

progressive neurodegeneration.
developmental delay (normal in first few months).
cherry-red spot on macula.
lysosomes with ONION SKIN.
**NO hepatosplenomegaly (vs. Niemann-Pick)

75

Krabbe's disease

LSD: sphingolipidosis.
AR inheritance.
deficient galactocerebrosidase.

accumulate: galactocerebroside and galactosyl sphingosine.

76

findings in Krabbe's

peripheral neuropathy.
developmental delay.
optic atrophy.
GLOBOID cells.

77

metachromatic leukodystrophy

LSD: sphingolipidosis.
AR inheritance.
deficient arylsulfatase A.

accumulate cerebroside sulfate.

78

findings in metachromatic leukodystrophy

central and peripheral demyelination with ataxia, dementia, muscle wasting

79

Hurler's syndrome

LSD: mucopolysaccharidosis.
AR inheritance.
deficient alpha-L-iduronidase.

accumulate: heparan sulfate, dermatan sulfate.

80

findings in Hurler's syndrome

developmental delay.
GARGOYLISM.
airway obstruction.
corneal clouding.
hepatosplenomegaly.

81

Hunter's syndrome

LSD: mucopolysaccharidosis.
XR inheritance.
deficient iduronate sulfatase.

accumulate: heparan sulfate, dermatan sulfate.

82

findings in Hunter's

mild Hurler's syndrome PLUS aggressive behavior with No corneal clouding

83

carnitine deficiency

inability to transport LCFA into mito.
toxic accumulation results.

84

features of carnitine deficiency

weakness.
hypotonia.
hypoketotic hypoglycemia.

85

acyl CoA dehydrogenase deficiency

increase dicarboxylic acids.
decrease glucose, ketones.

86

apo B-100

binds LDL receptor.
present in VLDL, IDL, LDL.

87

apo B-48

mediates chylomicron secretion by intestine.
present in chylomicron and remnant.

88

apo C-II

lipoprotein lipase cofactor.
present in chylo, VLDL, HDL.

89

apo A-I

activates LCAT for chol esterification.
present in chylo and HDL.

90

apo E 3, 4

mediate remnant uptake by liver.
present in all but LDL.

91

which lipoproteins carry most chol?

LDL and HDL

92

LDL transports chol from?

liver to tissues

93

HDL transports chol from?

periphery to liver

94

chylomicron

delivers dietary TGs to peripheral tissue.
also chol to liver via remnants, which are depleted of most TGs.

95

what cells secrete chylomicrons?

intestinal epith cells

96

VLDL

delivers hepatic TGs to peripheral tissues.

97

what secretes VLDL?

liver

98

IDL

formed as part of VLDL degrad.
delivers TGs and chol to liver where they are degraded to LDL.

99

LDL

delivers hepatic chol to peripheral tissue.

100

how is LDL formed?

lipoprotein lipase modification of VLDL in periphery

101

how is LDL taken up by peripheral target cells?

receptor-mediated endocytosis

102

HDL

mediates REVERSE chol transport from periphery to liver.

acts as repository for apoC and aloe whch are needed for chylomicron and VLDL metabolism.

103

what secretes HDL?

liver and intestine

104

familial dyslipidemia type I

hyper-CHYLOMICRONS.
elevated blood levels of TG and chol.
due to LPL deficiency or altered apoC-II.

105

findings in familial dyslipidemia type I

hyper-CHYLOMICRONS.

pancreatitis.
hepatosplenomegaly.
eruptive/pruritic xanthomas but NO INCREASED RISK for atherosclerosis.

106

familial dyslipidemia type IIa

familial hypercholesterolemia.
HIGH LDL.
elevated bld levels of chol.

auto dom.
absent or decreased LDL receptors in hepatocytes.

107

findings in familial dyslipidemia type IIa

familial hypercholesterolemia.

accelerated atherosclerosis.
early CAD.
tendon (achilles) xanthomas.
corneal arcus.

108

familial dyslipidemia type IV

hypertriglyceridemia.
HIGH VLDL.
increased bld levels of TG.
due to hepatic overproduction of VLDL.

causes PANCREATITIS.

109

abetalipoproteinemia

hereditary inability to make lipoproteins due to deficiencies in apoB-100 and B-48.

auto rec MTP mutation.
enterocytes unable to export lipoproteins and FFA.

110

findings in abetalipoproteinemia

appear in first few months of life.
failure to thrive.
steatorrhea.
acanthocytosis (spur cells).
ataxia.
night blindness.

111

abetalipoproteinemia intestinal BX

accumulation w/in enterocytes due to inability to export absorbed lipid as chylomicrons