more metabolism Flashcards
1
Q
what form of AAs are found in proteins?
A
L-form
2
Q
essential AAs
A
must come from diet.
Glucogenic: Val, Met, His, Arg.
Ketogenic: Lys, Leu.
Both: Ile, Phe, Thr, Trp, Tyr
3
Q
acidic AAs
A
Asp and Glu - neg charge at body pH
4
Q
basic AAs
A
His, Lys, Arg.
Arg is most basic.
His has no charge at body pH.
5
Q
which AAs are required during periods of growth?
A
His, Arg
6
Q
which AAs are increased in histones?
A
Arg, Lys - bind neg charged DNA
7
Q
AA catabolism yields?
A
common metabolites (pyruvate, acetyl CoA) that are used as fuel.
excess nitrogen (NH4+) that must be excreted.
8
Q
how is excess NH4+ from AA catabolism excreted?
A
converted to UREA,
excreted by kidneys
9
Q
contributors to urea structure
A
- NH4+
- CO2
- aspartate
10
Q
urea cycle intermediates (in order)
A
Ornithine. Carbamoyl phosphate. Citrulline. Aspartate. Argininosuccinate. Fumarate. Arginine. Urea.
“Ordinarily Careless Crappers Are Also Frivolous About Urination”
11
Q
hyperammonemia
A
results in excess NH4+
which depletes alpha-KG
leading to inhib of TCA cycle.
12
Q
causes of hyperammonemia
A
acquired: liver disease.
hereditary: urea cycle enz def.
13
Q
ammonium intoxication
A
tremor. slurred speech. somnolence. vomiting. cerebral edema. blurred vision.
14
Q
TX of hyperammonemia
A
- limit protein in diet.
- benzoate or phenylbutyrate: bind AA for excretion (bypass urea cycle), thus decreasing ammonia levels.
- lactulose: acidify GI lumen and trap NH4+ for excretion.
15
Q
ornithine transcarbamoylase deficiency
A
most common urea cycle d/o.
only X-linked recessive one.
interfere w/ability to eliminate ammonia.
16
Q
presentation of OTC def
A
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
Q
what happens to excess carbamoyl phosphate in OTC def?
A
converted to OROTIC ACID of pyrimidine synth pathway
18
Q
catecholamine cofactors
A
dopa to dopamine: B6.
dopamine to NE: vit C.
NE to epi: SAM.
19
Q
catecholamine breakdown products
A
via MAO and COMT.
dopamine: HVA.
NE: VMA.
epi: metanephrine.
20
Q
phenylketonuria (PKU)
A
due to decreased phenylalanine hydroxylase.
auto recessive. 1:10000.
21
Q
malignant PKU
A
due to decreased tetrahydrobiopterin (THB) cofactor
22
Q
what AA becomes essential in PKU?
A
tyrosine
23
Q
findings in PKU
A
mental retardation. growth retardation. seizures. fair skin. eczema. musty body odor.
increased phenylalanine = excess phenylketones in urine.
24
Q
what creates musty body odor in PKU?
A
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
