Cell Metabolism 2 Flashcards

1
Q

What are the 8 steps of the TCA cycle?
(citrate is a starting substrate for making oxaloacetate)

A
  1. Acetyl CoA —> Citrate
  2. Citrate —> Isocitrate
  3. Isocitrate —> a-Ketoglutarate
  4. a-Ketogluterate —> Succinyl CoA
  5. Succinyl CoA —> Succinate
  6. Succinate —> Fumerate
  7. Fumerate —> Malate
  8. Malate —> Oxaloacetate
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2
Q

What are the products of each turn of the TCA cycle?

A

2 CO2
3 NADH
1 FADH2
1 GTP

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3
Q

What is the property and location most of the TCA enzymes have in common?

A
  • Soluble
  • Mitochondrial Matrix
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4
Q

Is the TCA cycle aerobic?

A

Yes

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5
Q

What 7 products do amino acids degrade to? (AFA SOAP)

A
  1. Acetyl CoA
  2. Fumarate
  3. Acetoacetyl CoA
  4. Succinyl CoA
  5. Oxaloacetate
  6. a-Ketogluterate
  7. Pyruvate
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6
Q

What is a transamination reaction?

A

Amino acid + Keto acid —> Keto acid + Amino acid
- Group transfer

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7
Q

What transamination reaction occurs to alanine during metabolism?

A

Alanine + a-Ketogluterate —> Pyruvate + Glutamate
- Alanine aminotransferase

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8
Q

What occurs to each product of transamination of alanine?

A
  1. Pyruvate —> acetyl CoA
    - Decarboxylation
    - Enters TCA cycle
  2. Glutamate —> a-Ketogluterate
    - Glutamate dehydrogenase
    - NH4+ product —> urea
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9
Q

Where does the glycerol phosphate shuttle occur?

A
  1. Skeletal muscle
  2. Brain
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10
Q

Where do NADH electrons need to be transported?

A

Mitochondria

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11
Q

What are the 2 mechanisms for NADH transport?

A
  1. Glycerol phosphate shuttle
  2. Malate-aspartate shuttle
    (name order based on 2nd reaction)
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12
Q

Where does the malate aspartate shuttle occur?

A
  1. Liver
  2. Kidney
  3. Heart
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13
Q

What are the 3 stages of the glycerol phosphate shuttle cycle?

A
  1. DHAP + NADH —> G3P + NAD+
    - Cytoplasmic G3P dehydrogenase
  2. G3P + FAD —> DHAP + FADH2
    - Mitochondrial G3P dehydrogenase
  3. FADH2 + Q —> FAD + QH2
    - FAD regenerated for reaction step 2
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14
Q

What are the 2 stages of the malate-aspartate shuttle cylce?

A

1a. Aspartate + a-Ketoglutarate —> Oxaloacetate + Glutamate
- Aspartate transaminase
1b. Oxaloacetate + NADH —> Malate + NAD+
- Malate dehydrogenase

In via malate-a-ketoglutarate antiporter

2a. Malate + NAD+ —> Oxaloacetate + NADH
- Malate dehydrogenase
2b. Oxaloacetate + Glutamate —> Aspartate + a-Ketoglutarate
- Aspartate transaminase

Out via glutamate-aspartate antiporter

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15
Q

What type of reaction occurs throughout the glycerol phosphate shuttle?

A
  1. Redox
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16
Q

What 2 types of reaction occur throughout the malate aspartate shuttle?

A
  1. Redox
  2. Transamination
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17
Q

How many molecules of ATP are formed from NADH in oxidative phosphorylation?

A

3

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18
Q

How many molecules of ATP are formed from FADH2 in oxidative phosphorylation?

A

2

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19
Q

What are the products of oxidation of 1 acetyl CoA?

A

3 NADH
1 FADH2
1 GTP

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20
Q

How many ATPs can be generated from each acetyl CoA?

A

12

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21
Q

Which 3 TCA genes can have mutations that decrease TCA activity in cancer? (FIS)

A
  1. Isocitrate dehyrogenase
  2. Succinate dehydrogenase
  3. Fumerase
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22
Q

What is the Warburg Effect?

A

Lactate generation is preferential in cancerous cells so…
- Glycolysis inc
- TCA dec

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23
Q

What is the caloric yield from fatty acids compared to carbohydrates?

A

Double

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24
Q

What is fatty acid metabolism called?

A

B-Oxidation

25
Q

Where does B-oxidation occur?

A

Mitochondria

26
Q

What reaction do fatty acids undergo in step 1 of B-ox?

A

Fatty acid + ATP + HS-CoA —> Acyl CoA + AMP + PPi
- Acyl CoA Synthetase

27
Q

Where are fatty acids converted to acyl CoA species?

A

Outer mitochondrial membrane

28
Q

How are acyl CoA species transported into the mitochondrial matrix?

A

Carnitine shuttle

29
Q

What are the 2 stages in the carnitine shuttle cycle?

A
  1. Carnitine + Acyl CoA —> Acyl carnitine + CoA
    - Carnitine acyltransferase I
    - Translocase transports acyl carnitine into matrix
  2. Acyl carnitine + CoA —> Carnitine + Acyl CoA
    - Carnitine acyltransferase II
    - Translocase transports carnitine to cytoplasm
30
Q

Why does primary carnitine deficiency occur? (mutation)

A
  • Autosomal recessive
  • SLC22A5 gene mutation —> inhibits carnitine transporter
31
Q

What are the 3 symptoms of primary carnitine deficiency?

A

Encephalopathies
1. Cardiomyopathies
2. Muscle weakness
3. Hypoglycaemia

32
Q

What are the 4 reactions that occur in B-oxidation in order?

A
  1. Oxidation
  2. Hydration
  3. Oxidation
  4. Thiolysis
33
Q

What are the products of B-oxidation?

A

Acyl CoA 2 Cs shorter
1 Acetyl CoA

34
Q

How many B-ox reactions occur to palmitic acid and what happens in the last reaction?

A

7
- 4C fatty acyl CoA split into 2 acetyl CoA

35
Q

What is produced during each cycle of B-oxidation of palmitic acid?

A

1 NADH
1 FADH2
1 Acetyl CoA

36
Q

What is the overall reaction of the B-oxidation of palmitic acid?

A

Palmitoyl CoA + 7 CoA + 7 H2O + 7 NAD+ + 7FAD
—> 8 Acetyl CoA + 7 NADH + 7FADH2

37
Q

Why does B-oxidation rely on carbohydrate metabolism?

A

Oxaloacetate required for acetyl CoA to enter TCA cycle (because 8th product in cycle)

38
Q

What is produced when more fat is metabolised than carbohydrates?

A

Ketone bodies

39
Q

What are the 3 ketone bodies? (ADA)

A
  1. Acetoacetate
  2. 3-betahydroxybutyrate
  3. Acetone
40
Q

What is fatty acid biosynthesis called?

A

Lipogenesis

41
Q

Which 2 enzymes are used in lipogenesis?

A
  1. Acetyl CoA carboxylase
  2. Fatty acid synthase
42
Q

Which 2 reactants are used to form fatty acids?

A
  1. Acetyl-CoA
  2. Malonyl-CoA
43
Q

What are the 3 stages of lipogenesis?

A
  1. Elongation
  2. Reduction
  3. Dehydration
44
Q

Which 3 enzymes are involved in the reduction and dehydration of fatty acids? (Kill De Enemies)

A
  1. Ketoreductase (KR)
  2. Dehydratase (DH)
  3. Enol reductase (ER)
45
Q

What is a growing fatty acyl group linked to?

A

Acyl carrier protein

46
Q

What are the 3 differences between B-oxidation and lipogenesis? (CoLouR)

A
  1. Carriers: CoA vs acyl carrier protein
  2. Location: Mitochondrial matrix vs cytoplasm
  3. Reducing power: FAD/NAD vs NADPH
47
Q

What is the overall reaction of palmitate lipogenesis?

A

Acetyl CoA + 7 Malonyl CoA + 14 NADPH + 14 H+
—> Palmitate + 8 CoA-SH + 14 NADP+ + 7 CO2 + 6H2O

Think:
- 7 cycles for biosynthesis —> 7 for lipogenesis
- 7 NAD + 7 FAD for biosynthesis —> 14 NADPH for lipogenesis

48
Q

When does lipogenesis elongation occur?

A

Make fatty acids longer than palmitate (16C)

49
Q

Where does lipogenesis elongation occur?

A
  1. Mitochondria
  2. ER
50
Q

Which enzyme is required for desaturation?

A

Fatty acyl-CoA desaturases

51
Q

What does Δ-9 desaturase do and how?

A

Stearate + Palmitate —> Oleic acid + Palmitoleic acid
- makes double bond 9 Cs from terminal carboxyl group

52
Q

Where does fatty acid biosynthesis mainly occur in adults?

A
  1. Liver
  2. Adipose tissue
  3. Lactating breast
53
Q

What happens in cancer cells to fatty acid synthesis?

A

Reactivated in some

54
Q

What is an example of inhibiting fatty acid synthesis to reduce tumour size?

A

Cerulenin (antifungal antibiotic) for ovarian cancer cells

55
Q

What are the 4 types of acyl CoA dehydrogenases?

A
  1. Short-chain… (<6C)
  2. Medium-chain… (C6-C12)
  3. Long-chain… (C13-C21)
  4. Very long-chain… (>C22)
56
Q

What is MCADD and how should it be controlled?

A
  • Autosomal recessive
  • Can be fatal (1/100 SIDS)
  • Food every 10-12 hours
  • High carb diet
57
Q

How is MCADD screened?

A

Heel prick test

58
Q

How must MCADD patients be treated when ill with appetite loss or severe vomiting?

A

I.V. glucose so body not dependant on fatty acids for energy