metabolism Flashcards
(116 cards)
1
Q
what are the 3 pathways of ethanol metabolism?
A
1) cytosolic: alcohol DH and acetaldehyde DH
2) microsomal: CYP2E1
3) peroxisomal: catalase
2
Q
limiting reagent in ethanol metabolism?
A
NAD+
3
Q
what are the downstream effects of ETOH metab?
A
1ary: increased NADH/NAD+ ratio –>
lactic acidosis (pyruvate –> lactate)
fasting hypoglycemia (OAA –> malate - prevents gluconeo)
hepatosteatosis (DHAP –> G3P)
increased use of AcCoA for ketogenesis and lipogenesis
4
Q
what metabolic processes happen in the mitochondria?
A
FA oxidation AcCoA production TCA cycle OxPhos ketogenesis
5
Q
what metabolic processes happen in the cytoplasm?
A
glycolysis FA synthesis HMP shunt protein synthesis (RER) steroid synthesis (SER) cholesterol synthesis
6
Q
what metabolic processes happen in both mito and cytoplasm?
A
heme synthesis
urea cycle
gluconeogenesis
7
Q
rate determining enzyme of glycolysis?
A
PFK!
+: AMP, F26BP
-: ATP, citrate
8
Q
rate determining enzyme of gluconeo?
A
F16BPase
+: ATP, AcCoA
-: AMP, F26BP
9
Q
rate determining enzyme of TCA?
A
isocitrate DH
+: ADP
-: ATP, NADH
10
Q
rate determining enzyme of glycogenesis?
A
glycogen synthase
+: G6P, insulin, cortisol
-: epi, glucagon
11
Q
rate determining enzyme of glycogenolysis?
A
glycogen phosphorylase
+: epi, glucagon, AMP
-: G6P, insulin, ATP
12
Q
rate determining enzyme of HMP shunt?
A
G6PD
+: NADP
-: NADPH
13
Q
rate determining enzyme of pyrimidine synth?
A
carbamoyl P synthetase II
+ ATP
- UTP
14
Q
rate determining enzyme of purine synth?
A
glutamine-PRPP amidotransferase
- AMP, IMP, GMP
15
Q
rate determining enzyme of urea cycle?
A
carbamoyl P synthetase I
+ N-acetyl glutamate
16
Q
rate determining enzyme of FA synthesis?
A
AcCoA carboxylase
+ insulin, citrate
- glucagon, palmitoyl-CoA
17
Q
rate determining enzyme of FA oxidation?
A
carnitine acyltransferase I
- malonyl CoA
18
Q
rate determining enzyme of ketogenesis?
A
HMG CoA synthase
19
Q
rate determining enzyme of cholesterol synthesis?
A
HMG CoA reductase
+ insulin, thyroxine
- glucagon, cholesterol
20
Q
ATP prod in aerobic metabolism vs anaerobic?
A
aerobic (malate-asp shuttle, heart/liver) - 32
aerobic (G3P shuttle, muscle) - 30
anaerobic - 2
arsenic - 0
21
Q
what do CoA and lipoamide carry?
A
acyl groups
22
Q
what does biotin carry?
A
CO2 - carboxylation rxns
23
Q
what do THFs carry?
A
1-carbon units
24
Q
what does SAM carry?
A
methyl groups
25
what does TTP carry?
aldehydes
26
what types of processes is NAD+ used in?
catabolic processes - carrying reducing equivalents
27
what types of processes is NADPH used in?
anabolic
respiratory burst
CYP450
glutathione reductase
28
where is hexokinase found?
most tissues except liver and pancreatic beta cells
29
where is glucokinase found
liver, beta cells of pancreas
30
which of hexo/glucokinase is induced by insulin?
glucokinase
31
which of hexo/glucokinase is inhibited by G6P?
hexokinase
32
what cofactors are needed by pyruvate DH (and a-KG DH)?
1. TPP - thiamine/B1
2. FAD - riboflavin/B2
3. NAD - niacin/B3
4. CoA - pantothenic acid/B5
5. lipoic acid (inhibited by arsenic)
33
increased serum alanine in infancy, lactic acidosis, neurologic defects?
pyruvate DH deficiency - X-linked
pyruvate builds up --> lactate and alanine
tx: increase ketogenic intake (lysine, leucine)
34
what cofactor does alanine aminotransferase need?
B6 (pyridoxine)
35
what cofactor does lactic acid DH need?
B3 (niacin)
36
where is anaerobic metabolism the major pathway?
```
RBC
WBC
kidney medulla
lens
testes
cornea
```
37
what is the order of products of the TCA?
```
citrate
isocitrate
a-KG
succinyl CoA
succinate
fumarate
malate
OAA
```
38
which complex of the ETC does rotenone inhibit?
complex I
39
which complex of the ETC does antimycin A inhibit?
complex III
40
which complex of the ETC do cyanide and CO inhibit?
complex IV
41
which complex of the ETC does oligomycin inhibit?
complex V (ATP synthase)
42
which agents are ETC uncoupling agents?
2,4 Dinitrophenol
aspirin
thermogenin
43
which are the irreversible enzymes of gluconeogenesis?
pyruvate carboxylase (mitochondria)
PEP carboxykinase
F16BPase
G6Pase (ER)
44
which are the enzymes of the oxidative/irreversible portion of the HMP shunt?
G6PD!
45
which are the enzymes of the nonoxidative/reversible portion of the HMP shunt? what cofactor do they need?
transketolases
phosphopentose isomerase
require THIAMINE!
46
fructose in blood and urine, asx/mild?
essential fructosuria - AR
| defect in fructokinase
47
hypoglycemia, jaundice, cirrhosis, vomiting; sx after fruit/juice/honey, negative urine dipstick but reducing substance in urine?
fructose intolerance - AR
defect in aldolase B
F1P accumulates in cells, available P decreases --> no glycogenolysis or gluconeogenesis
tx: no fructose or sucrose in diet
48
infantile cataracts, no other sx?
galactokinase deficiency - AR
| mild, accumulation of galactitol with ingestion of galactose
49
infantile cataracts, intellectual disability, FTT, jaundice, hepatomegaly, E. coli sepsis?
classic galactosemia - AR
absence of gal-1-P uridyltransferase
tx: no galactose or lactose in diet
50
which tissues do not have sorbitol DH?
schwann cells, retina, kidneys, lens
51
cause of primary lactase deficiency?
absence of lactase persistent allele
age-dependent decline following childhood
Asians, Africans, Native Americans
52
causes of 2ary lactase deficiency?
loss of brush border: gastroenteritis, autoimmune
53
which are the essential AAs?
LEUcy and LYSa MET VAL on HIS TRiP THRough the IsLE of PHoEnix
54
which are the ketogenic AAs?
leu
| lys
55
which are the glucogenic AAs?
met
val
his
56
which are the acidic AAs?
asp
| glu
57
which are the basic AAs?
HAL is a basic guy
his
arg
lys
58
which AAs are required during growth?
Arg
| His
59
which AAs are in histones?
Arg
| Lys
60
what is the order of products/substrates in the urea cycle?
Ordinarily Careless Crappers Are Also Frivolous About Urination
```
ornithine
+ carbamoyl phosphate
citrulline
+ aspartate
argininosuccinate
- fumarate
arginine
- urea
```
61
what is the cofactor for transamination to a-KG/glutamate?
B6 (pyridoxine)
62
what is the Cahill cycle?
transfer of ammonia via alanine
- transamination from glu --> ala in mm
- ala travels to liver
- transamination from ala --> glu --> urea cycle
63
what is the Cori cycle?
- glucose --> pyruvate --> lactate in mm
- reverse in liver
related to Cahill cycle - ammonia transfer from mm to liver
64
neonate with poorly regulated respiration and body temp, poor feeding, developmental delay, intellectual disability?
N-acetylglutamate synthase deficiency (or carbamoyl phosphate synthetase I deficiency)
65
hyperammonemia symptoms, increased orotic acid in blood and urine, decreased BUN, no megaloblastic anemia?
OTC deficiency - XLR
excess carbamoyl P converted to orotic acid
* * orotic aciduria: megaloblastic anemia
* * other urea cycle deficits: AR
66
derivatives of trp, and cofactors needed?
niacin - needs B6
| serotonin/melatonin - needs B6 and BH4
67
derivatives of his, and cofactors needed?
histamine - needs B6
68
derivatives of gly, and cofactors needed?
porphyrin --> heme, needs B6
69
derivatives of glu, and cofactors needed?
GABA - needs B6
| glutathione
70
derivatives of arginine, and cofactors needed?
creatine
urea
NO - B6 needed
71
intellectual disability, growth retardation, seizures, fair skin, eczema, MUSTY body odor?
PKU - AR
defect in phe hydroxylase or decreased BH4 cofactor
avoid aspartame, decrease phenylalanine, increase tyrosine
BH4 supplementation
72
sweet urine, severe CNS defects, intellectual disability?
MSUD - AR
branched chain AA degradation blocked - defective a-ketoacid DH (needs thiamine as cofactor)
tx: restrict BCAAs, thiamine supplementation
73
which are the branched chain AAs?
ILE
LEU
VAL
74
black pee, dark connective tissue, brown sclerae, arthralgia?
alkaptonuria - AR
deficiency of homogentisate oxidase (tyr degradation pathway)
usually benign
75
Marfanoid habitus, osteoporosis, kyphosis, downward lens subluxation, thrombosis, atherosclerosis?
homocystinuria - AR
- cystathionine synthase deficiency (tx: dec MET, inc CYS, B12, folate)
- decreased cyst synth affinity for PLP (tx: inc B6 and CYS)
- homocysteine methyltransferase deficiency (tx: inc MET)
76
hexagonal urinary stones, + urinary cyanide nitroprusside test?
cystinuria - AR
defect of AA transport - increased excretion of COLA
tx: alkalinize urine (K citrate, acetazolamide)
chelate with penicillamine
hydrate
77
glycogen regulation by glu/epi
1) glu --> glucagon rcptr (liver), epi--> alpha (liver) and beta (liver and mm) rcptr
2) cAMP increase and Ca increase (from epi at alpha)
3) PKA activated from cAMP
4) PKA and Ca activate glycogen phosphorylase kinase
5) glycogen phosphorylase activated
6) PKA --> glycogen synthase inactivated
78
glycogen regulation by insulin
1) insulin binds tyr-kinase dimer rcptr (liver and mm)
2) downstream activation of protein phosphatase and glycogen synthase
3) protein phosphatase activates glycogen synthase and deactivates glycogen phosphorylase
79
what types of bonds are in the branches of glycogen?
alpha 1,6
80
what types of bonds are in the linkages of glycogen?
alpha 1,4
81
what enzymes are involved in glycogenolysis?
1) glycogen phosphorylase: active until 4 units remaining on branch ("limit dextrin")
2) 4-a-D-glucanotransferase moves 3 units branch --> linkage
3) a-1,6-glucosidase cleaves last unit --> glucose liberated
82
severe fasting hypogly, high glycogen in liver, lactate in blood, TGemia, increased uric acid, hepatomegaly?
VonGierke's - type I GSD, AR
glucose-6-phosphatase deficient
tx: frequent oral glucose/cornstarch; avoid fructose and galactose
83
cardiomegaly, HOCM, exercise intolerance, early death?
Pompe's - type II GSD, AR
lysosomal a-1,4-glucosidase deficiency
** Pompe trashes the Pump: heart, liver, muscle
84
milder VonGierke, normal blood lactate?
Cori - type III GSD, AR
deficient a-1,6-glucosidase
** gluconeogenesis is intact
85
painful muscle cramps, myoglobinuria, arrhythmia?
McArdle's - type V GSD, AR
deficient MUSCLE glycogen phosphorylase
blood glucose usually normal
tx: B6 (cofactor)
86
hand/foot neuropathy, angiokeratomas, CV/renal dz?
Fabry disease, XR
deficient a-galactosidase A
accumulation of ceramide trihexoside
87
HSM, pancytopenia, osteoporosis, aseptic necrosis of femur, lipid-laden macrophages, bone crises?
Gaucher dz - AR
deficient glucocerebrosidase
accumulation of glucocerebroside
** tx: recombinant glucocerebrosidase
88
neurodegeneration, HSM, foam cells, cherry-red spot?
Niemann-Pick, AR
deficient sphingomyelinase
accumulation of sphingomyelin
89
neurodegeneration, NO HSM, cherry red spot, onion skin lysosomes?
Tay Sachs, AR
deficient hexosaminidase A
accumulation of GM2 ganglioside
90
peripheral neuropathy, developmental delay, optic atrophy, globoid cells?
Krabbe disease, AR
deficient galactocerebrosidase
accumulation of galactocerebroside, psychosine
91
central and peripheral demyelination with ataxia and dementia?
metachromic leukodystrophy, AR
deficient arylsulfatase A
accumulation of cerebroside sulfate
92
developmental delay, gargoylism, airway obstruction, corneal clouding, HSM?
Hurler dz, AR
deficient a-L-iduronidase
accumulation of heparan sulfate and dermatan sulfate
93
like Hurler but with aggressive behavior and no corneal clouding?
Hunter dx, XLR
deficient iduronate sulfatase
accumulation of heparan sulfate and dermatan sulfate
94
weakness, hypotonia, hypoketotic hypoglycemia?
systemic 1ary carnitine deficieny
| defect in LCFA transport into mitochondria --> toxic accumulation
95
which are the essential FAs?
linoleate
| alpha-linolenate
96
citrate shuttle is required for which process?
FA synthesis (transport from mito to cytosol)
97
carnitine shuttle is required for which process?
FA degradation (transport from cytosol to mito)
98
infancy/childhood with vom, lethargy, sz, coma, liver dysfunction, hypoketotic hypoglycemia, 8-10-C FA-carnitines in blood?
medium-chain acyl-coA DH deficiency, AR
minor illness --> sudden death
tx: AVOID FASTING
99
main source of blood glucose in days 1-3 of starvation?
glycogen depleted after day 1
| hepatic glycogenolysis, adipose FFA, muscle/liver use of FFAs, hepatic gluconeogenesis --> maintain blood glucose
100
main source of energy after day 3 of starvation?
adipose stores
| KBs main source for brain
101
can RBCs use ketones for energy?
NO! don't have mitochondria
102
what are products of cholesterol?
bile acids
steroids
vit D
103
what does pancreatic lipase do?
degrades dietary TGs in small intestine
104
what does LPL do?
produced by adipose cells, found in vascular endothelium
| degrades TGs in CMs and BLDLs
105
what does HL do?
hepatic
| degrades TGs in IDL in periphery
106
what does HSL do?
degrades TGs stored in adipocytes
107
what does LCAT do?
catalyzes esterification of cholesterol --> load HDL with cholesterol from peripheral tissues
activated by apoA
108
what does CETP do?
mediates transfer of cholesterol esters from HDL to other lipoproteins
109
what do chylomicrons do?
dietary TG--> peripheral tissues
chol --> liver (via CM remnants)
secreted by intestinal epithelial cells
110
what does VLDL do?
delivers hepatic TG to peripheral tissue
111
what does IDL do?
delivers TGs and chol to liver
112
what does LDL do?
delivers hepatic chol to periphery
| taken up via receptor-mediated endocytosis (apoB100 binds LDL receptor)
113
what does HDL do?
chol transport from periphery to liver
repository for apoC and apoE --> CM and VLDL
secreted by liver and gut
**alcohol causes increased synthesis of HDL
114
pancreatitis, HSM, eruptive/pruritic xanthomas W/O atherosclerosis, creamy supernatant?
hyperchylomicronemia, AR
| LPL deficiency or altered apoCII
115
accelerated atherosclerosis (MI <20yo), tendon xanthomas, corneal arcus?
familial hypercholesterolemia, AD
absent/defective LDL receptors
heterozygotes chol ~300, homozygotes ~700+
116
very very high TGs?
hypertriglyceridemia, AD
hepatic overproduction of VLDL
** TGs>1000 --> pancreatitis
