11b: Biochem metabolism Flashcards
1
Q
List the metabolic pathways that occur only in mitochondria
A
“FAT OK”
- FA (beta) ox
- Acetyl-CoA production
- TCA cycle
- Ox phos
- Ketogenesis
2
Q
List the metabolic pathways that occur in both cytoplasm and mito
A
“HUGs take two”
- Heme synthesis
- Urea cycle
- Gluconeogenesis
3
Q
Difference between phosphorylase and kinase
A
Kinase catalyzes PO4 group transfer from HIGH E molecule (ex: ATP)
Phosphorylase transfers inorganic PO4 without using ATP
4
Q
Dehydrogenase enzymes catalyze (X) reactions
A
X = Redox
5
Q
Rate-determining enzyme of gluconeogenesis
A
Fruc-1,6-bisphosphatase
6
Q
Rate-determining enzyme of TCA cycle
A
Isocitrate dehydrogenase
7
Q
Rate-determining enzyme of de novo purine synthesis
A
Gln-PRPP amidotransferase
8
Q
Rate-determining enzyme of FA synthesis
A
Acetyl-CoA carboxylase
9
Q
Rate-determining enzyme of FA ox
A
Carnitine acyltransferase I
10
Q
Rate-determining enzyme of Ketogenesis
A
HMG-CoA synthase
Note: in cholesterol synthesis, it’s HMG-CoA reductase
11
Q
List the positive regulators of PFK-1
A
AMP and Fructose-2,6-bisphosphate
neg regulators are citrate, ATP
12
Q
List the positive regulators of Fructose-1,6-bisphosphatase
A
Citrate
neg regulators: AMP and Fructose-2,6-bisphosphate = the pos regulators for PFK-1
13
Q
Glycogen synthase positive regulators:
A
Gluc-6P, insulin, cortisol
the negative regulators of glycogen phosphorylase except cortisol
14
Q
Glycogen synthase negative regulators:
A
Epi, glucagon
the positive regulators of glycogen phosphorylase
15
Q
Carbamoyl phosphate synthetase I regulator:
A
N-acetylglutamate (pos regulator)
Note: urea cycle enzyme
16
Q
Acetyl-CoA carboxylase neg regulators
A
Glucagon and palmitoyl-CoA
17
Q
Carnitine acyltransferase I neg regulator
A
Malonyl-CoA
18
Q
T/F: Thyroxine is positive regulator of HMG-CoA reductase
A
True
19
Q
(X) chemical element causes glycolysis to produce zero net ATP
A
X = arsenic
20
Q
RBCs can run glycolysis without generating any ATP. What’s the function of this?
A
Create 2,3-BPG from 1,3-BPG via BPG mutase;
2,3-BPG can then be converted into 3-phosphoglycerate and return to glycolysis, but no ATP made
21
Q
CoA and lipoamide are important carrier molecules for:
A
Acyl groups
22
Q
Biotin is important carrier molecule for:
A
CO2
23
Q
THF is important carrier molecule for:
A
1-C units
24
Q
S-adenosylmethionine (SAM) is important carrier molecule for:
A
CH3 (methyl) groups
25
(Hexokinase/glucokinase) found in most tissues except (X)
Hexokinase;
| X = beta cells of pancreas, liver
26
(Hexokinase/glucokinase) has higher affinity for glucose and (higher/lower) capacity/Vmax
Hexokinase (lower Km); lower Vmax
27
(Hexokinase/glucokinase) induced by insulin and (Hexokinase/glucokinase) neg regulation by Gluc-6P
Glucokinase
| Hexokinase
28
Co-factors for Pyruvate Dehydrogenase
"Tender Loving Care For Nancy"
1. TPP (Thiamine pyrophosphate)
2. Lipoic acid (inhibited by arsenic)0
3. CoA
4. FAD
5. NAD
29
Rx for Pyruvate DH deficiency
Increase intake of ketogenic nutrients (high fat content or high Lys/Leu); generation of Acetyl-CoA instead of Pyruvate
30
Alanine can be converted to Pyruvate via (X) enzyme which requires (Y) cofactor. In the process, alanine's (Z) group is given to:
X = ALT (alanine aminotransferase)
Y = B6
Z = amino
alpha-KG (to form Glu)
31
Which TCA cycle enzymes are irreversible?
Citrate synthase
Isocitrate DH
alphaKG DH
32
ETC: Complex IV is inhibited by...
CN, CO
| "CN and CO inhibit complex four"
33
ETC: Complex I is inhibited by...
Rotenone
"rotenONE inhibits complex ONE"
34
ETC: Complex (X) is the ATP synthase
X = V
35
List some examples of ETC uncouplers
1. Dinitrophenol (illicitly used for weight loss)
2. Aspirin OD (hence fevers)
3. Thermogenin (in brown fat)
Remember, uncouplers cause high O2 consuption and heat generation
36
Irreversible enzymes of gluconeogenesis. Where is the location of each?
1. Pyruvate carboxylase (mito)
2. PEP carboxykinase (cytosol)
3. Fructose-1,6-bisphosphatase (cytosol)
4. Glucose-6 phosphatase (ER)
37
T/F: Muscle, kidney, and liver can participate in gluconeogenesis.
False - not muscle (lacks gluc-6 phosphatase)
38
(Odd/even)-chain FAs can participate in gluconeogenesis
Odd (can generate propionyl-CoA which enters TCA as succinyl-CoA)
Note: Even-chain FAs only generate Acetyl-CoA so can't participate
39
Aldolase B, deficient in (X) disorder, is responsible for which conversion/reaction?
X = fructose intolerance
Fructose 1P to DHAP and glyceraldehyde
40
Which essential AAs are solely glucogenic?
Met, His, Val
"I Met His Valentine, she is so sweet (glucogenic)"
41
(X) AAs are especially required during periods of growth. (Y) AAs are high in histones.
```
X = Arg, His
Y = Arg, Lys (basic so bind neg charged DNA)
```
42
The Cori cycle is an exchange of Glucose and (X) by which two organs?
X = Lactate
| Muscle (gives lactate to liver) and Liver (gluconeogenesis to give glucose back to muscle)
43
The Cahill cycle is an exchange of Glucose and (X) by which two organs?
X = Alanine
Muscle (makes Ala from pyruvate and gives it to liver) and Liver (makes pyruvate and then glucose via gluconeogenesis to give back to muscle)
44
Most common urea cycle disorder:
```
Ornithine Transcarbamylase (OTC) deficiency;
orotic acid high in blood/urine WITH hyperammonemia
```
45
Why is orotic acid (low/high) in Ornithine Transcarbamylase (OTC) deficiency?
Buildup of carbamoyl phosphate get shunted to pyrimidine synthesis pathway and converted to orotic acid
46
Phe to Tyr requires (X) cofactor. Tyr to Dopa requires (Y) cofactor. Dopa to DA requires (Z) cofactor.
```
X = Y = BH4 (tetrahydrobiopterin)
Z = B6
```
47
Melanin made from (X), which is made from (Y)
```
X = Dopa (via tyrosinase)
Y = Tyr (via tyrosine hydroxylase)
```
48
DA to NE synthesis requies (X) cofactor. NE to Epi requires (Y) cofactor
```
X = Vit C
Y = SAM (methyl donation; hence, name of enzyme is PNMT, Phenylethanolamine-N-methyltransferase)
```
49
Patient with Sx of PKU also have elevated prolactin levels. What's going on?
BH4 deficiency (can't convert Phe into Tyr or Tyr into DOPA, so low DA levels means high prolactin)
50
Melatonin made from which AA?
Trp (via SA synthesis then melatonin from SA)
51
(B6/BH4) required for SA synthesis from Trp
Both
52
Heme synthesis starts off with which two substrates?
Gly and Succinyl CoA
53
Glutathione made from which AA?
Glu
54
Patient with (X) metabolic disorder can't have (Y) artificial sweetener because it contains:
X = PKU
Y = aspartame
Phe
55
Maple syrup urine disease Rx:
Restrict Ile, Leu, Val; supplement Thiamine
56
Patient with blue-black ear cartilage/sclerae and black urine upon exposure to air. Which enzyme deficiency?
Alkaptonuria; deficient homogentisate oxidase (involved in Tyr degradation to fumarate)
57
List the three different types of homocystinuria
1. Cystathione synthase deficiency
2. Methionine synthase deficiency
3. Low affinity of cystathionine synthase for PRP (cofactor involving B6)
58
Cystathione synthase deficiency causes (X) disorder and should be treated with:
X = homocystinuria
Low methionine (since homocysteine is being shunted down that pathway); high Cys, B6, B12, and folate supplementation
59
Glycogenolysis in muscle stimulated by (phosphorylase/phosphatase) activation by (X).
Glycogen phosphorylase
X = Ca (directly) and Epi (via cAMP)
*Ca more powerful activator
60
Glycogenolysis in liver stimulated by (phosphorylase/phosphatase) activation by (X)
Glycogen Phosphorylase
| X = Epi and glucagon (via cAMP)
61
30 yo M with bilateral ptosis, facial muscle atrophy, and stiff/delayed muscle relaxation after handshake. Father has similar, but less severe, Sx.
Myotonic dystrophy (CTG tri-NT expansion)
62
Stage (X) of sleep is referred to as "restorative" sleep, important for rejuvenation of the brain. If reduced, patient will complain of (Y)
```
X = 3 (deep/delta/slow-wave) NREM
Y = not feeling rested
```
Declines significantly (almost vanishes) in elderly
63
T/F: REM sleep declines significantly as one ages.
False - tends to stay relatively constant (at 20%) until about 80 yo, then declines
64
High anti-RNP (aka anti-U1 ribonucleoprotein) Ab is specific for:
Mixed connective tissue disease
65
Glycogen synthesis: glucose 1P becomes (X) with action of (Y) enzyme
```
X = UDP-glucose
Y = UDP glucose pyrophosphorylase
```
66
Glycogenolysis: list the two debranching enzymes and the function of each
1. 4aD-glucanotransferase: removes 3/4 glucose residues from branch on limit dextrin until there's only 1 glucose left on it
2. alpha-1,6-glucosidase: removes last glucose residue on branch
67
Von Gierke's disease: which enzyme deficient? Which metabolic pathway(s) impaired?
Glucose-6-phosphatase
Gluconeogenesis and glycogenolysis
68
Rx for Von Gierke disease
Frequent oral glucose/cornstarch; avoid fructose and galactose
69
Pompe disease: which enzyme deficient? Which metabolic pathway(s) impaired?
Acid alpha-1,4-glucosidase aka acid maltase (a lysosomal enzyme)
Glycogenolysis
70
Cori disease is a (mild/severe) form of (X) with which enzyme deficiency? Which metabolic pathway(s) impaired?
Mild
X = von gierke disease
```
Debranching enzyme (alpha-1,6-glucosidase)
Glycogenolysis (but gluconeogenesis is intact)
```
71
Which glycogen storage disease will likely cause patient to be in metabolic acidosis?
Von Gierke (high lactic acid)
72
Triad: neuropathic pain, decreased sweating (hypohidrosis), and dark red, non-blanching papules over groin/butt/umbilicus. Which disease?
Fabry disease (alpha-galatosidase A deficiency)
Skin findings = angiokeratomas
73
Long-term consequence of Fabry disease
Progressive renal failure and CV disease
74
Which substrate is accumulating in Fabry disease?
Ceramide trihexoside (a sphingolipid)
75
Metachromatic leukodystrophy is deficiency in (X)
Lysosomal storage disease
X = Arylsulfatase A
(accumulation of cerebroside sulfate)
76
Krabbe disease: which enzyme deficient?
Galactocerebrosidase (accumulation of galactocerebroside)
77
Lysosomal storage disease with Sx of ataxia and dementia due to central/peripheral demyelination
Metachromatic leukodystrophy
78
Lysosomal storage disease with Sx of optic atrophy, developmental delay, peripheral neuropathy. Destruction of oligodendrocytes.
Krabbe
79
"Crumpled tissue paper" cells seen in (X) storage disease are actually what kind of cells?
X = Gaucher (lysosomal storage disease)
Lipid-laden macrophages
80
Gaucher disease: which enzyme deficient?
Glucocerebrosidase (beta-glucosidase); accumulated substrate is Glucocerebroside
81
Which lysosomal storage disease has Sx of osteoporosis, avascular necrosis and bone crises?
Gaucher disease
82
FA synthesis requires (X) shuttle and FA degradation requires (Y) shuttle.
```
X = citrate (citrate leaves mito and enters cytoplasm)
Y = carnitine (Acyl-CoA enters mito for beta-ox)
```
83
FA undergo beta-oxidation and (X) key enzyme converts them to (Y)
```
X = Acyl-CoA Dehydrogenase
Y = Acetyl-CoA
```
84
Triglyceride stored in adipose is broken down into glycerol and FFA by which enzyme?
Hormone-sensitive lipase
85
In well-fed state, FA (ox/synth) is inhibited via (X) inhibition of (Y) shuttle.
Oxidation
X = malonyl-coa
Y = carnitine
86
Which tissues can't use ketone bodies?
1. Erythrocytes (no mitochondria)
| 2. Liver (lacks enzyme)
87
Urine test for ketones detects:
Acetoacetate (can't detect beta-hydroxybutyrate)
88
Metabolic fuel use: stored ATP depleted in (X) amount of time and Creatine phosphate in (Y) amount of time
```
X = 2 s
Y = 10 s
```
89
Glycogen reserves depleted after (X) day(s) starvation. (Fat/protein) is consumed at more rapid rate throughout the subsequent days/weeks of starvation.
X = 1
| Fat
90
After (X) days of starvation, adipose stores/ketone bodies become main source of E
X = 3
91
Lipoprotein lipase is found on/in which cells?
On vascular endothelial surface
| degrades TGs circulating in chylomicrons/VLDLs
92
Which enzyme is responsible for nascent HDL conversion to mature HDL?
LCAT (esterifies plasma cholesterol so that HDL can then transfer cholesterol esters to other lipoproteins)
93
Which enzyme is responsible for cholesterol ester transfer from HDL to other lipoproteins??
CETP (Cholesterol Ester Transfer Protein)
94
Alcohol increases synthesis of which lipoprotein?
HDL
95
Abetalipoproteinemia: loss of function of (X). It's important to supplement with (Y) for treatment
X = MTP (microsomal TG transfer protein; necessary for proper apoB folding/lipid transfer to chylomicrons/VLDL)
Y = large doses of vit E (deficiency of this vit causes spinocerebellar degeneration)
96
Familial dysplipidemia: Sx of pancreatitis, hepatosplenomegaly, and creamy layer (milky plasma) in supernatant.
Hyper-chylomicronemia (AR; LPL or apolipoprotein C-II deficient)
97
T/F: All familial dysplipidemias increase risk for atherosclerosis.
False - Hyperchylomicronemia and hyper-TG don't increase atherosclerosis risk
98
Which familial dysplipidemias increase risk for early MI?
1. Familial hypercholesterolemia (absent/defective LDL R)
| 2. Dysbeta-lipoproteinemia (defective ApoE)
