Fatty acid breakdown + beta-oxidation

Question 1

Activation of Fatty acids for breakdown

Answer 1

FA + ATP + CoASH -> Acyl CoA + AMP + PPi

• enzyme: ACYL CoA SYNTHETASE
• in cytosol
• costs 2ATP

Question 2

Carnitine-Mediated transport of Acyl CoA

Answer 2

1. Acyl-CoA + Carnitine -> Acyl-Carnitine + CoASH
   - enzyme: CARNITINE ACYLTRANSFERASE 1 CAT1
   - RATE LIMITING
   - cytosol
   - through carnitine-acylcarnitine translocase (CACT)
2. Acyl-carnitine + CoASH -> Acyl-CoA + Carnitine
   - enzyme: CAT2
   - matrix
   - carnitine back

Question 3

Regulation of Carnitine Acyltransferase 1

Answer 3

Rate limiting

inhibited by: Malonyl-CoA

Question 4

Carnitine deficiency

Answer 4

systemic:

1. primary: OCTN2 deficiency: hypoglycemia, ketosis
2. secondary: Methylmalonyl defect, B12 vitamin defect: hypoglycemia, metabolic acidosis
   myopathic: impaired uptake

Question 5

1. Acyl-CoA -> Trans-Enoyl-CoA

Answer 5

• oxidation
• FAD->FADH2
• enzyme: ACYL CoA DEHYDROGENASE

Question 6

2. Trans-Enoyl-CoA -> L-beta-hydroxyacyl-CoA

Answer 6

• hydration +H2O

- enzyme: ENOYL CoA HYDRATASE

Question 7

3. L-beta-hydroxyacyl-CoA -> beta-Ketoacyl-CoA

Answer 7

• oxidation
• NAD+ -> NADH
• enzyme: B-HYDROXYACYL CoA DEHYDROGENASE

Question 8

4. beta-ketoacyl-CoA -> Acyl-CoA (proprionyl-CoA) + Acetyl CoA

Answer 8

• cleavage
• +CoASH
• enzyme: THIOLASE

Question 9

Acyl-CoA DH deficiency

Answer 9

1:40 1 mutation
1:10000 2 mutation
hypoglycemia, decrease ketone body formation, accumulation of lipids in liver, vomiting, drowsiness
Treatment: carbohydrate-rich meals, carnitine supply

Question 10

Proprinoyl CoA

Answer 10

1. proprionyl CoA + CO2 + ATP -> Methyl-malonyl CoA + ADP
   - proprionyl CoA carboxylase (Biotin)
2. Methyl-malonyl CoA -> Succinyl CoA
   - methyl-malonyl CoA mutase
   - > TCA

Question 11

Regulation of Beta-oxidation

Answer 11

1.Hormones: increase oxidation
glucagon,epinephrine-> inhibition of perilipin, activation of HSL -> increase FFA in blood
2. High energy state: decrease oxidation
high malonyl CoA -> inhibition of CAT1
high NADH-> inhibition of 3hydroxyacyl CoA DH
high Acetyl-CoA -> thiolase