Chapter 26 Oxidation of Fatty Acids

brapa pathway oxidation of fatty acids?

1.beta oxidation (major)

2.peroxisomal oxidation

3.alpha oxidation

4.w (omega) oxidation

Beta oxidation of FA

E kena release dari FA

si acyl coA kena oxidised pg acetyl coA

kena panggil b O sebab oxidation start at b carbon atom of FA

Location B O

Tissues: liver, muscle, renal cortex, adrenal medulla, heart etc

intracellular site: mitochondria

brapa stage B oxidation?

1. activation of Fatty acid

2. transport of fatty acyl coA into mitochondria

3. degradation (b- oxidation reactions)

1. activation of Fatty acid

Fatty acid + CoA-SH —> Fatty acyl CoA guna enzyme thiokiase dan perlu Mg2+

2. transport of fatty acyl coA into mitochondri

Guna carnitine shuttle. hafal picture dia sebab ini sangat penting

Reactions of β-oxidation

• Reactions of β-oxidation:

  • Cyclical process

  • Four reactions per cycle: Oxidation, Hydration, Reoxidation, Thiolytic cleavage

  • Each cycle removes 2 carbon compound as acetyl CoA

  • Repeated cycles break down fatty acyl CoA to acetyl CoA

Oxidation

1. Oxidation:

• Acyl CoA dehydrogenase converts fatty acyl CoA to Δ2 trans enoyl CoA using FAD

Hydration

2. Hydration:

• Δ2 trans enoyl CoA is hydrated to 3-hydroxyacyl CoA by Δ2 -enoyl-CoA hydratase

Reoxidation

3. Reoxidation:

• 3-hydroxyacyl CoA is dehydrogenated to 3-ketoacyl-CoA by -3-ketoacyl-CoA dehydrogenase using NAD+

Cleavage

4. Cleavage:

• 3-ketoacyl-CoA is cleaved by thiolase to produce acetyl-CoA and acyl CoA derivative

• Acyl-CoA re-enters pathway for further degradation to acetyl CoA via citric acid cycle

End product of B oxidation

Even no. C atom: Acetyl coA

Odd no. C atom: Acetyl coA and propionyl coA

Energetic of beta oxidation

Palmitic acid is the commonly occurring fatty acid in the food and body

E yang kena hasil dari palmitic acid (guna Beta O)

1 NADPH = 2.5 ATP

1 FADH2 = 1.5 ATP

1 cycle of Beta O produced 4 ATP

7 cycle of Beta O produced 7×4= 28 ATP

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A total of 8 acetyl coA are produced; each one enters TCA cycle and gives 10 ATP.

8 Acetyl coA: 8×10 ATP= 80 ATP

Therefore 28 ATP + 80 ATP = 108 ATP

But the activation of fatty acid utilizes 2 high energy bonds. So, the net production of ATP from palmitic acid: 108-2= 106 ATP

Biomedical importance

1. Carnitine deficiency

   1. infants yang ada renal leakage

   2. symptom dia hypoglycemia, muscle weakness dan lipid accumulation

   3. treatment: oral supplementation of carnitine

2. Hepatic CPT 1 deficiency

   1. hypoglycemia and low plasma ketone bodies

3. Hepatic CPT 2 deficiency

   1. muscle weakness and myoglobinuria

4. Jamaican vomiting sickness

   1. eating unripe ackee tree. ni ada toxin hypoglycin yang inhibit beta oxidation dan cause hypoglycemia

5. Decarboxylic aciduria lead to excretion of dicarbocylic acids. sebab dia ada acyl coA dehydrogenase deficiency

6. Refsum’s disease - inherited defect alpha oxidation that allow accumulation of phytanic acid

7. Zellweger’s syndrome (cerebrohepatorenal) inherited deficiency of peroxisomes