Cell Metabolism 2 Flashcards
What are the 8 steps of the TCA cycle?
(citrate is a starting substrate for making oxaloacetate)
- Acetyl CoA —> Citrate
- Citrate —> Isocitrate
- Isocitrate —> a-Ketoglutarate
- a-Ketogluterate —> Succinyl CoA
- Succinyl CoA —> Succinate
- Succinate —> Fumerate
- Fumerate —> Malate
- Malate —> Oxaloacetate
What are the products of each turn of the TCA cycle?
2 CO2
3 NADH
1 FADH2
1 GTP
What is the property and location most of the TCA enzymes have in common?
- Soluble
- Mitochondrial Matrix
Is the TCA cycle aerobic?
Yes
What 7 products do amino acids degrade to? (AFA SOAP)
- Acetyl CoA
- Fumarate
- Acetoacetyl CoA
- Succinyl CoA
- Oxaloacetate
- a-Ketogluterate
- Pyruvate
What is a transamination reaction?
Amino acid + Keto acid —> Keto acid + Amino acid
- Group transfer
What transamination reaction occurs to alanine during metabolism?
Alanine + a-Ketogluterate —> Pyruvate + Glutamate
- Alanine aminotransferase
What occurs to each product of transamination of alanine?
- Pyruvate —> acetyl CoA
- Decarboxylation
- Enters TCA cycle - Glutamate —> a-Ketogluterate
- Glutamate dehydrogenase
- NH4+ product —> urea
Where does the glycerol phosphate shuttle occur?
- Skeletal muscle
- Brain
Where do NADH electrons need to be transported?
Mitochondria
What are the 2 mechanisms for NADH transport?
- Glycerol phosphate shuttle
- Malate-aspartate shuttle
(name order based on 2nd reaction)
Where does the malate aspartate shuttle occur?
- Liver
- Kidney
- Heart
What are the 3 stages of the glycerol phosphate shuttle cycle?
- DHAP + NADH —> G3P + NAD+
- Cytoplasmic G3P dehydrogenase - G3P + FAD —> DHAP + FADH2
- Mitochondrial G3P dehydrogenase - FADH2 + Q —> FAD + QH2
- FAD regenerated for reaction step 2
What are the 2 stages of the malate-aspartate shuttle cylce?
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
What type of reaction occurs throughout the glycerol phosphate shuttle?
- Redox
What 2 types of reaction occur throughout the malate aspartate shuttle?
- Redox
- Transamination
How many molecules of ATP are formed from NADH in oxidative phosphorylation?
3
How many molecules of ATP are formed from FADH2 in oxidative phosphorylation?
2
What are the products of oxidation of 1 acetyl CoA?
3 NADH
1 FADH2
1 GTP
How many ATPs can be generated from each acetyl CoA?
12
Which 3 TCA genes can have mutations that decrease TCA activity in cancer? (FIS)
- Isocitrate dehyrogenase
- Succinate dehydrogenase
- Fumerase
What is the Warburg Effect?
Lactate generation is preferential in cancerous cells so…
- Glycolysis inc
- TCA dec
What is the caloric yield from fatty acids compared to carbohydrates?
Double
What is fatty acid metabolism called?
B-Oxidation
Where does B-oxidation occur?
Mitochondria
What reaction do fatty acids undergo in step 1 of B-ox?
Fatty acid + ATP + HS-CoA —> Acyl CoA + AMP + PPi
- Acyl CoA Synthetase
Where are fatty acids converted to acyl CoA species?
Outer mitochondrial membrane
How are acyl CoA species transported into the mitochondrial matrix?
Carnitine shuttle
What are the 2 stages in the carnitine shuttle cycle?
- Carnitine + Acyl CoA —> Acyl carnitine + CoA
- Carnitine acyltransferase I
- Translocase transports acyl carnitine into matrix - Acyl carnitine + CoA —> Carnitine + Acyl CoA
- Carnitine acyltransferase II
- Translocase transports carnitine to cytoplasm
Why does primary carnitine deficiency occur? (mutation)
- Autosomal recessive
- SLC22A5 gene mutation —> inhibits carnitine transporter
What are the 3 symptoms of primary carnitine deficiency?
Encephalopathies
1. Cardiomyopathies
2. Muscle weakness
3. Hypoglycaemia
What are the 4 reactions that occur in B-oxidation in order?
- Oxidation
- Hydration
- Oxidation
- Thiolysis
What are the products of B-oxidation?
Acyl CoA 2 Cs shorter
1 Acetyl CoA
How many B-ox reactions occur to palmitic acid and what happens in the last reaction?
7
- 4C fatty acyl CoA split into 2 acetyl CoA
What is produced during each cycle of B-oxidation of palmitic acid?
1 NADH
1 FADH2
1 Acetyl CoA
What is the overall reaction of the B-oxidation of palmitic acid?
Palmitoyl CoA + 7 CoA + 7 H2O + 7 NAD+ + 7FAD
—> 8 Acetyl CoA + 7 NADH + 7FADH2
Why does B-oxidation rely on carbohydrate metabolism?
Oxaloacetate required for acetyl CoA to enter TCA cycle (because 8th product in cycle)
What is produced when more fat is metabolised than carbohydrates?
Ketone bodies
What are the 3 ketone bodies? (ADA)
- Acetoacetate
- 3-betahydroxybutyrate
- Acetone
What is fatty acid biosynthesis called?
Lipogenesis
Which 2 enzymes are used in lipogenesis?
- Acetyl CoA carboxylase
- Fatty acid synthase
Which 2 reactants are used to form fatty acids?
- Acetyl-CoA
- Malonyl-CoA
What are the 3 stages of lipogenesis?
- Elongation
- Reduction
- Dehydration
Which 3 enzymes are involved in the reduction and dehydration of fatty acids? (Kill De Enemies)
- Ketoreductase (KR)
- Dehydratase (DH)
- Enol reductase (ER)
What is a growing fatty acyl group linked to?
Acyl carrier protein
What are the 3 differences between B-oxidation and lipogenesis? (CoLouR)
- Carriers: CoA vs acyl carrier protein
- Location: Mitochondrial matrix vs cytoplasm
- Reducing power: FAD/NAD vs NADPH
What is the overall reaction of palmitate lipogenesis?
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
When does lipogenesis elongation occur?
Make fatty acids longer than palmitate (16C)
Where does lipogenesis elongation occur?
- Mitochondria
- ER
Which enzyme is required for desaturation?
Fatty acyl-CoA desaturases
What does Δ-9 desaturase do and how?
Stearate + Palmitate —> Oleic acid + Palmitoleic acid
- makes double bond 9 Cs from terminal carboxyl group
Where does fatty acid biosynthesis mainly occur in adults?
- Liver
- Adipose tissue
- Lactating breast
What happens in cancer cells to fatty acid synthesis?
Reactivated in some
What is an example of inhibiting fatty acid synthesis to reduce tumour size?
Cerulenin (antifungal antibiotic) for ovarian cancer cells
What are the 4 types of acyl CoA dehydrogenases?
- Short-chain… (<6C)
- Medium-chain… (C6-C12)
- Long-chain… (C13-C21)
- Very long-chain… (>C22)
What is MCADD and how should it be controlled?
- Autosomal recessive
- Can be fatal (1/100 SIDS)
- Food every 10-12 hours
- High carb diet
How is MCADD screened?
Heel prick test
How must MCADD patients be treated when ill with appetite loss or severe vomiting?
I.V. glucose so body not dependant on fatty acids for energy
