Metabolic biochem Flashcards
(152 cards)
1
Q
phosphorylase
A
adds inorganic phosphate w/out using ATP
2
Q
mutase
A
relocates functional group within a molecule
3
Q
rate determining step of glycolysis
+ and - regulators
A
phosphofructokinase-1
PFK-1
+: AMP, fructose-2,6-bisphosphate
-: ATP, citrate
4
Q
rate determining step of gluconeogenesis
+ and - regualtors
A
Fructose-1,6-bisphosphatase
+: ATP, acetyl-CoA
-: AMP, fructose-2,6-bisphosphate
5
Q
rate determining step of TCA cycle
+ and - regulators
A
Isocitrate dehydrogenase
+: ADP
-: ATP, NADH
6
Q
rate determining step of glycogenesis
+ and - regulators
A
Glycogen synthase
+: G6P, insulin, cortisol
-: epi, glucagon
7
Q
rate determining step of glycogenolysis
+ and - regulators
A
Glycogen phosphorylase
+: epi, glucagon, AMP
-: G6P, insulin, ATP
8
Q
rate determining step of HMP shunt
+ and - regulators
A
G6PD
+: NADP+
-: NADPH
9
Q
rate determining step of de novo pyrimidine synthesis
A
Carbamoyl phosphate synthetase II
10
Q
rate determining step of de novo purine synthesis
+ and - regulators
A
glutamine-phosphoribosylpyrophosphate (PRPP) synthetase
-: AMP, IMP,. GMP
11
Q
rate determining step of urea cycle
+ and - regulators
A
Carbamoyl phosphate synthetase I
+: N-acetylglutamate
12
Q
rate determining step of FA synthesis
+ and - regulators
A
Acetyl-CoA Carboxylase (ACC)
+: insulin, citrate
-: glucagon, palmiotoyl-CoA
13
Q
rate determining step of FA oxidation
+ and - regulators
A
Carnitine acyltransferase I
-: malonyl-CoA
14
Q
rate determining step of ketogenesis
A
HMA-Coa synthase
15
Q
rate determining step of cholesterol synthesis
+ and - regulators
A
HMA-CoA reductase
+: insulin, thyroxine
-: glucagon, cholesterol
16
Q
connection between urea cycle and TCA cycle
A
fumarate, a byproduct in the urea cycle can enter TCA to become malate before OAA
17
Q
connection between glycolysis, TCA, and Fa synthesis
A
acetyl-CoA
18
Q
NADPH
- product of what pathway
- used for what?
- ROS?
A
- HMP shunt
- used in anabolic processes, respiratory burst, cyt p450 system, glutathione reductase
- creation and neutralization of ROS
19
Q
Glucokinase
- where is it found?
- insulin effect
- G6P effect
A
- liver and beta cells of pancreas
- insulin induces it
- no feedback inhibition from G6P
20
Q
Hexokinase
- where is it found?
- insulin effect
- G6P effect
A
- most tissues, but not liver or beta cells of pancreas
- insulin doesn’t affect it
- negative inhibition from G6P
21
Q
gene mutation a/w maturity onset diabetes of the young (MODY)
A
Glucokinase
22
Q
glycolysis yields #ATP # NADH
A
2 ATP
2 NADH
23
Q
what step in glycolysis gives NADH
A
G3P or DAG –> 1,3-BPG
24
Q
pyruvate dehydrogenase reaction
A
pyruvate + NAD + CoA –> acetyl-CoA + CO2 + NADH
25
what enzymes does the pyruvate dehydrogenase complex contain (3) and what cofactors do they need
what is it activated by
1. pyruvate dehydrogenase (thiamine pyrophosphate (TPP)
2. dihydrolipoyl transacetylase (lipoate and CoA)
3. dihydrolipoyl dehydrogenase (FAD and NAD)
increased NAD/NADH; ADP; and Ca
26
what does FAD need?
B2
27
What does NAD need?
B3
28
what does CoA need
B5
29
pyruvate dehydrogenase complex deficiency
- leads to?
- findings?
- tx?
- buildup of pyruvate that is shunted to lactate and alanine (LDH and ALT)
- neuro defects, lactic acidosis, increased serum alanine in infancy
- increase intake of ketogenic nutrients (high fat content or high lysine and leucine content)
30
what are the only purely ketogenic aa's?
lysine and leucine
31
Alanine aminotransferase (ALT)
- needs what?
- what does it do
- b6 (pyridoxine)
| - pyruvate to Alanine carries amino groups to liver from muscle
32
pyruvate carboxylase
- needs what
- what does it do
- b7 (biotin)
| - pyruvate to OAA that can replenish TCA or be used in gluconeogenesis
33
pyruvate dehydrogenase
- needs what
- what does it do
- b1, 2, 3, 5, lipoic acid
| - transition from glycolysis to TCA
34
LDH
- needs what
- what does it do
- b3 (niacin)
| - end of anaerobic glycolysis (used in RBCs, leukocytes, renal medulla, lens, testes, cornea)
35
NADH makes how many ATP in ETC
what ETC structure?
2.5
complex I
36
FADH2 makes how many ATP in ETC
what ETC structure?
1.5
complex II (succinate dehydrogenase)
37
direct ETC inhibitors
-mechanism
rotenon (complex I)
cyanide (complex IV)
antimycin A (complex III)
CO (complex IV)
blocks complexes and prevents production of proton gradient
38
ATP synthase inhibitors
oligomycin
39
Uncoupling agents
- what does that mean
- ex
- lets H leak across inner mito MB, so weaker proton gradient ... produces heat
- 2,4-dinitrophenol, aspirin overdose --> causes fever
40
irreversible enzymes of gluconeogenesis (4)
- whats the rxn
- what do they need
1. pyruvate carboxylase: pyr to OAA (bitoin, ATP, acetyl-CoA)
2. PEP caryboxykinase: OAA to PEP (GTP)
3. F1,6BPase: F1,6BP to F6P (citrate)
4. G6Pase (in the ER): G6P to glucose
41
HMP shunt
- provides what? (2)
- ATP?
1. NADPH for redox rxns
2. ribose for nucleotide synthesis
- ATP neither used nor produced
42
Two phases of HMP shunt
oxidative: irreversible; rate-limiting step w/G6P dehydrogenase
non oxidative: reversible, w/pPEP isomerase and transketolases to make Ribulose 5-P from Ribose 5P
43
respiratory burst
- what does it involve?
- what cells?
- substrate?
- immune response rapid release of ROS
- NADH oxidase complexes in neutrophils and monocytes
- O2
44
myeloperoxidase
- what color?
- what is it
blue-green heme-containing pigment
| gives sputum its color
45
enzymes of respiratory burst
1. NADPH oxidase (O2 to superoxide)
2. Superoxide dismutase (superoxide to peroxide)
3. myeloperoxidase or catalase or diffusion
4. Glutathione Peroxidase (uses glutathione to cut peroxide)
5. Glutathione reductase (reduces glutathione using NADPH)
6. G6PD (reduces NADP+ using G6P)
46
chronic granulomatous disease
pts with the condition cannot generate ROS, so at greater risk of chronic infections by catalse + organisms that can neutralize ROS
47
G6PD def and ROS
it's the end point of ROS, so without it, cannot properly protect from oxidative damage
48
oxidizing agents that can damage RBCs in G6PD def pts (4)
1. fava beans
2. sulfonamides
3. chemo drugs
4. primaquine
49
heinz bodies
- what are they?
- where are they seen?
- precipitated oxidized Hb
| - G6PD def
50
Bite cells
| - what happened?
they're RBCs that have had chunks taken out in attempt to remove Heinz bodies
51
Enzymes of fructose metabolism (3)
- where does it occur
1. fructokinase: fructose to F-1P
2. Aldolase B: F-1P to DHAP or Glyceraldehyde
3. Triose kinase: Glyceraldehyde to G-3P
- liver
52
Essential fructosuria
- inheritance
- what is it
- sxs
- AR
- defect in fructokinase
- basically asymptomatic
53
Fructose intolerance
- inheritance
- what is it
- sxs
- why?
- AR
- def in aldolase B
- hypoGly, jaundice, cirrhosis, vomiting
- accumulation of F-1P in liver
54
Enzymes of galactose metabolism (3-4)
1. Galactokinase: galactose to Gal-1P
2. Uridyltransferase: Gal-1P to Glu-1P
3. Aldose reductase: galactose to galactitol (the alcohol counterpart)
4. 4-Epimerase: involved in the switching of UDP-Gal and UDP-Glu
55
Galactokinase deficiency
- inheritance
- what enzyme involved
- what happens
- AR
- hereditary def of galactokinase
- accumulation of galactitol, which acts as an osmotic agent so can get inftaile cataracts
56
Classic galactosemia
- inheritance
- what is what enzyme involved
- what happens
- what can it lead to
- AR
- absence of Gal-1P uridyltransferase
- accumulation of Gal-1P and galactitol in lens and liver
jauntice, MR, cataracts, FTT
- can lead to E. Coli sepsis in neonates
57
Sorbitol
- what is it
- purpose?
- enzymes involved in its metabolism (2)
- glucose's alcohol counterpart
- traps glucose in cells
- Aldose reductase (glucose to sorbitol using NADPH) + Sorbitol dehydrogenase (sorbitol to fructose using NADP+)
58
What cells have both enzymes of sorbitol metabolism (3)
1. liver
2. ovaries
3. seminal vesicles
59
what cells have only the first enzyme of sorbitol metabolism (3)
1. schwann cells (so can get peripheral neuropathy)
2. Retina (so you can get retinopathies)
3. renal cells
60
types of lactase deficiency (3)
1. primary
2. secondary
3. congenital lactase deficiency
61
Primary lactase deficiency
age-dependent decline after childhood (absence of lactase-persistent allele) common in Asians, AfAms, and NatAms
62
Secondary lactase deficiency
loss of brush border 2/2 gastroenteritis (rotavirus), autoimmune disease etc
63
Congenital lactase deficiency
rare... 2/2 defective gene
64
stool of lactase def pts
acidic
65
Types of esssential AA's (3)
1. glucogenic
2. glucogenic/ketogenic
3. ketogenic
66
glucogenic AA's (3)
Met, Val, His
67
ketogenic AA's (2)
Leu, Lys
68
keto/glucogenic AA's (4)
Ile, Phe, Thr, Trp
69
Acidic AA's (2)
| - what's their charge?
Asp and Glu
| - negatively charged at body pH
70
Basic AA's (2)
- what's most basic
- what's their charge
Arg, Lys, His
Arg most basic
no charge at body pH
71
Carbamoyl phosphate synthetase I
- what cycle is it a part of
- what reaction
- cofactor
- urea cylce
- CO2 and NH3 to Carbamoyl phosphate
- N-acetylglutamate
72
where is excess nitrogen converted to urea
| where is it excreted
liver
kidney
73
Order of urea cycle
```
1. Co2+NH3
add N-acetylglutamate
2. carbamoyl phosphate
add ornithine
3. citrulline
add Aspartate and ATP
4. Argininosuccinate
deposit fumarate
5. Arginine
deposit urea
6. ornithine
back to mitochondria
```
74
what amino acids required for periods of growth? (2)
Arg and His
75
Ammonia shuttling
- what aa's important
- from where to where
- 2 cycles
- glutamate and alanine
- NH3 from aa's to urea for excretion
- muscle to liver
- alanine and cori cycle
76
alanine cycle of ammonia shuttle
1. pyruvate to Ala by acquiring NH3 from glutamate as it becomes a-KG
2. alanine leaves muscle and goes to liver
3. in liver: Ala to pyruvate by giving a-KG NH3 to become glutamate
4. pyruvate becomes glucose
5. glucose sent to muscles
6. glucose becomes pyruvate
REPEAT
77
Cori cycle
muscle: glucose --> pyruvate --> Lactate
lactate travels to liver
liver: Lactate --> pyruvate --> glucose
glucose goes to muscle
REPEAT
78
hyperammonemia
- depletes that?
- therefore that is inhibited?
- alpha-Ketoglutarate
| - TCA cycle inhibited
79
what treats hyperammonemia by binding and excreting aa's
benzoate or phenylbutyrate
80
mechanism of lactulose
acidifies GI tract to trap NH4+ for excretion
81
Ammonia intoxication s/s's
asterixis, slurring, somnolence, vomiting, cerebral edema, blurry vision
82
N-acetylglutamate
- required for what enzyme
- what cycle
- what happens if there's def?
- carbamoyl phosphate synthetase I
- urea cycle
- hyperammonemia
83
How to differentiate b/w N-acetylglutamate def and carbamoyl phosphate synthetase I def?
normal urea cycle enzymes, but elevated ornithine levels
84
Ornithine transcarbamylase
| - what does it do
combines ornithine and carbamoyl phosphate into citrulline in the urea cycle
85
most common urea cycle d/o?
ornithine transcarbamylase def
86
Ornithine transcarbamylase def
- inheritance
- what accumulates
- what is it converted to, in what pathway
- findings?
- XRecessive
- excess carbamoyl phosphate
- converted to orotic acid in pyrimidine synthesis pathway
- elevated orotic acid in blood and urine; sxs of hyper-ammonemia; decreased BUN (b/c can't get to urea)
87
connection b/w urea cycle and pyrmidine synthesis pathway
carbamoyl phosphate
88
difference in findings b/w ornithine transcarbamylase def and orotic aciduria
orotic aciduria has megaloblastic anemia b/c it's a defect in the nucleic acid synthesis pathway
89
difference b/w orotic aciduria and b12 deficiency
both have megaloblastic anemia 2/2 NT synthesis def, but orotic aciduria will be unresponsive to B12 therapy
90
essential amino acid derivative of catecholamines
| - what is it turned into in the body to serve as the starting aa for catecholamines
phenylalanine
tyrosine
91
essential amino acid derivative of NAD/NADP
tryptophan
92
essential amino acid derivative of melatonin
- what makes melatonin
tryptophan
- tryptophan --> 5-HT --> melatonin
93
essential amino acid derivative of heme
- what's in b/w that and heme
glycine
porphyrin
94
essential amino acid derivative of GABA and glutathione
glutamate
95
essential amino acid derivative of creatine
arginine
96
essential amino acid derivative of urea
arginine
97
essential amino acid derivative of nitric oxide
arginine
98
what co-factor most used while taking amino acid derivates to their biological workers
vitamin b6 (pyridoxine)
99
phenylalanine hydroxylase
- what reaction
- a/w what condition
- how to treat that condition
- phenylalanine to tyrosine (catecholamine synthesis)
- PKU (phenylketonuria) b/c excess phenylalanine
- need exogenous Tyrosine and decrease phenylalanine
100
why musty odor in PKU?
phenylalanine is an aromatic amino acid that accumulates --> leads to odor
101
what must pts with PKU also avoid?
| - what dietary thing has phenylalanine?
artificial sweeteners
102
how does phenylalanine get to TCA cycle?
Phe --> Tyr --> homogentisic acid --> methylacetoacetic acid --> TCA
103
how is albinism a/w catecholamine synthesis?
- what enzyme
Melanin comes from this cycle (from DOPA; from Tyrosine; from Phe) via Tyrosinase
104
enzymes of catecholamine synthesis
phenylalanine hydroxylase, tyrosine hydroxylase, tyrosinase, DOPA decarboxylase
105
carbidopa blocks what
- what disease used for
- why does it work for that dz
- blocks DOPA decarboxylase
- used in Parkinson's
- blocks peripheral conversion of levodopa to dopamine so that there's max delivery of levodopa to CNS
106
findings of PKU
- Mr, growth ret, sz, fair skin, eczema, musty odor
107
3 of the phenylketones
1. phenyl - acetate
2. phenyl - lactate
3. phenyl - pyruvate
108
Alkaptonuria
- what is it
- findings
- d/o of metabolism of what
- congenital def in homogentisate oxidase
- dark connective tissue, brown sclera, urine black on air exposure
- maybe joint issues b/c homogentisic acid toxic to cartilage
- tyrosine to fumarate into TCA
109
Homocystinuria vs. Cystinuria
- cystinuria is just renal issues so you get crystals
| - homocystinuria is metabolic issue of homocysteine metabolism, so more disease
110
Homocystinuria
- def enzymes
- s/s's
- cystathione synthase
OR
homocysteine methyltrasnferase def
- homocystinuria, MR, osteoporosis, kyphosis, thrombosis, atherosclerosis 2/2 endothelial injury
111
Treating cystinuria
- urinary alkylinzation (w/K-citrate or acetazolamide)
- chelating agents
- good hydration
112
Maple syrup urine disease
- inheritance
- what is blocked
- what enzyme affected
- presentation
- tx
- AR
- degradation of branched AAs is blocked
- alpha-ketoacid dehydrogenase (B1)
- elevated ketoacids in blood; MR, death, CNS defects
- dietary restriction and thiamine supplementation
113
Cystathionine synthase
- what reaction
- what does it need
- homocysteine to cystathionine
| - Serine and Vit B6
114
homocysteine methyltransferase
- what reaction
- what does it need
- homocysteine to methionine
| - Vit B12
115
what are the branched AA's
Isoleucine
Leucine
Valine
"I Love Vermont Maple tree branches"
116
glycogen metabolism
| - what enzymes what do they do
- PKA: activates glycogen phosphorylase kinase
- glycogen phosphorylase kinase: activates glycogen phosphorylase
- glycogen phosphorylase: glycogen to glucose
- glycogen synthase: glucose to glycogen
117
what bonds do glycogen branches have
alpha (1,6)
118
what bonds to glycogen linkages have
alpha (1,4)
119
glycogenolysis
- what cells have it
- what's the reaction
glycogen to glu-1P
| muscles and liver
120
debranching of glycogen
1. phosphorylase takes off G-1Ps from branches until 4 left
2. Debranching enzyme (4-alpha-glucanotransferase) takes 3 off and adds it to linkage
3. Debranching enzyme (alpha-1,6-glucosidase) takes off the last one
121
Fatty acid synthesis: what shuttle
| - what enzymes
Citrate shuttle
"SYtrate" = "SYNthesis"
- ATP citrate lyase
122
Fatty acid degradation: what shuttle
| what enzymes
Carnitine
"CARNitine = CARNage"
- FA CoA synthetase
- beta ox enzymes (acyl-CoA dehydro, etc, thiolase)
123
Carnitine def
- inability to?
- presents with?
- inability to break down long FA's ... so toxic accumulation
- weakness, hypotonia, hypoketotic hypoglycemia
124
Acyl-CoA dehydrogenase def
- inability to?
- presents with?
- inability to start beta-oxidation in the mitochondria
| - low acetyl-CoA, therefore low fasting glucose, low TCA and low ketones
125
Malonyl-coa in synthesis and degradation of FA
synthesis: acetyl-coa into malonyl-coa before formation of FA's
degradation: malonyl-coa negatively inhibits carnitine shuttle
126
Ketone bodies
- examples (3)
- made in? from?
- used for?
- acetoacetic acid
- beta-hydroxybutyric acid
- acetone
- made in liver from FA degradation and AA's metabolism
- acetoacetic acid and beta-hydroxybutyric acid used as energy for brain, heart, muscle in low glucose states
127
What is depleted during starvation and DKA states to undergo gluconeogenesis
- what is built up
OAA
- acetyl-coa --> ketone bodies
128
how does alcoholism lead to ketonosis
excess NADH from lactate dehydrogenase --> shunts OAA to malate
buildup of acetly-coa --> ketone bodies
129
beta oxidation
| - acetyl-coa products go where?
Ketone bodies
or
TCA
130
urine test for ketones tests for which one
acetone and acetoacetic acid
131
how long can glycogen reserves last?
1 day
132
how many days starvation before degrading vital proteins?
> 3 days
133
HMG-CoA reductase
- reaction
- insulin effect
- HMG-CoA to mevalonate
| - insulin induces it
134
LCAT?
lectithin-cholesterol acyltransferase
| 2/3 of plasma cholesterol is esterified by this
135
which lipoproteins carry most choletserol (2)
LDL and HDL
136
lipoproteins made of what?
cholesterol
TGs
phospholipids
137
chylomicron
- delivers what
- where to where
- how does it get to liver
- excreted how
- dietary TGs
- GI to peripheral tissue
- chylomicron remnants
- intestinal epithelia
138
VLDL
- delivers what
- where to where
- excreted how
- hepatic TGs
- liver to peripheral tissue
- liver
139
IDL
- how formed
- delivers what where to where
- formed in degradation of LDL
| - delivers TG and cholesterol to liver
140
LDL
- delivers what
- where to where
- formed by?
- hepatic cholesterol
- liver to peripheral tissue
- hepatic lipase mod's IDL in peripheral tissue
LDL-Rec endocytosis
141
HDL
- delivers what
- where to where
- secrete where?
- alcohol effect
- cholesterol
- peripheral tissue to liver
- secreted from liver and intestine
- increases HDL synthesis
142
Apolipoproteins (5)
1. E
2. A-I
3. C-II
4. B-48
5. B-100
143
ApoE
- function
- which lipoproteins?
- mediates remnant uptake
| - chylo, chylo remnant, VLDL, IDL, HDL
144
ApoA-I
- function
- which lipoproteins
- activates LCAT
| - chylo, HDL
145
ApoC-II
- function
- which lipoproteins
- LPL (lipoprotein lipase) cofactor
| - chylo, VLDL, HDL
146
ApoB-48
- function
- which lipoproteins
- mediates chylomicron secretion
| - chylo, chlyo remnant
147
ApoB-100
- function
- which lipoproteins
- binds LDL rec
| - VLDL, IDL, LDL
148
Familial dyslipidemias in First AID (3)
1. I-hyperchylomicronemia
2. IIa-familial hypercholesterolemia
3. IV-hypertriglyceridemia
149
I-hyperchylomicronemia
- inheritance
- high levels of what in blood
- 2/2?
- presentation
- AR
- chylomicron, TG, cholesterol
- LPL or ApoC-II def
- HSM, pancreatitis, pruritic xanthomas, no atherosclerosis
150
IIa-familial hypercholesterolemia
- inheritance
- high levels of what in blood
- 2/2?
- presentation
- AD
- Chol, LDL
- absent or mutated LDL receptor
- atherosclerotic dz, tendon xanthomas, corneal arcus
151
IV-hypertriglyceridemia
- inheritance
- high levels of what in blood
- 2/2?
- presentation
- AD
- TG, VLDL
- hepatic overproduction of VLDL
- pancreatitis
152
Glucagonoma
- what cells does it arise from
- presentation (3)
- dx
-alpha cells pancreas
- 1. necrolytic migratory erythema
2. DM
3. GI sxs (diarrhea, anorexia, abd pain
- elevated glucagon
