Case details
A 5- year-old boy suffered gastroenteritis for two days and was brought to the emergency in the semiconscious state. Blood glucose at the time of admission was 45 mg/dl and his urine was negative for glucose and ketone bodies. Glucose was administered intravenously and his condition improved within 10 minutes. Subsequent laboratory investigations revealed elevated acylcarnitine residues. The child was diagnosed with an enzyme deficiency. The parents were instructed to feed the child more frequently.
Which of the following enzymes might be deficient?
- Acyl Co A synthetase
- Carnitine Acyl transferase-1
- Translocase
- Carnitine Acyl transferase-2
- Acyl co A dehydrogenase
The correct answer is- A. Acyl co A dehydrogenase.
Acyl co A synthetase catalyzes the activation of fatty acid to form Fatty acyl co A, the active form of fatty acid (figure-1).
Figure-1- reaction catalyzed by Acyl co A synthetase
Carnitine Acyl transferase-1(CAT-1), Translocase and Carnitine Acyl transferase-2(CAT-2) are the components of the carnitine shuttle (figure-2) which is required for the transportation of fatty acyl co A across the inner mitochondrial membrane.
a) CAT-1 catalyzes the conversion of Acyl co A to Acyl carnitine.
b) Translocase transports acylcarnitine across the inner mitochondrial membrane in exchange for carnitine.
c) CAT-2 catalyzes the conversion of Acyl carnitine back to Acyl co A, the form that is required for the beta-oxidation of acyl co A by the enzymes present in the mitochondrial matrix.
Figure-2- Role of carnitine in the transport of long-chain fatty acids through the inner mitochondrial membrane. Long-chain acyl-CoA cannot pass through the inner mitochondrial membrane, but its metabolic product, acylcarnitine, can cross through with the help of a carnitine shuttle. CPT (Carnitine palmitoyl transferase), is specific for Palmitic acid, which is the most abundant fatty acid, AND Acyl is a general term for fatty acid.
Mitochondrial beta-oxidation is a cyclic process. In each cycle, the fatty acyl co A is subjected to four chemical processes. Two carbons are removed as Acetyl co A from the parent compound in each cycle. The chemical processes involved in each cycle are :
1) Dehydrogenation
2) Hydration
3) Dehydrogenation, and
4) Thiolytic cleavage.
These cycles are repeated, till the fatty acid is completed broken down to the final two carbon compounds.
Acyl co A dehydrogenase is the first enzyme in the cyclic process of beta-oxidation. It catalyzes the conversion of acyl co A to α,β Unsaturated Acyl co A.
The deficiency of Acyl co A dehydrogenase impairs beta-oxidation.
Hypoglycemia in this condition is a consequence of impaired fatty acid oxidation with the resultant imbalance between demand and supply of glucose which is the sole of the source of energy in such individuals.
