Question

it has been observed that malonyl-CoA inhibits palmitic acid oxidation in isolated mitochondria, but that it has little or no effect on the oxidation of octanoic acid ( C8, saturated). Explain this observation.

Answer 1

• Fatty acid metabolism occurs in mitochondria and peroxisomes.
• Thus, to be oxidized, fatty acids should first enter the organelle, which is mediated by fatty acid protein transporters associated with the membrane surface.
• To enter the mitochondrial matrix, long chain fatty acids should be trans esterified and require coupling to carnitine.
• This is mediated by the carnitine palmitoyl-transferase I (CPT-I).
• CPT-I convert, long chain fatty acyl-CoA to long chain acylcarnitine.
• This allows the long chain fatty acid to be transported across the inner mitochondrial membrane with the aid of carnitine translocase (CAT).
• Palmitic acid or Hexadecenoic acid, is a long chain fatty acid. Thus, to enter the mitochondria for oxidation process, it requires CPT-I for its coupling with carnitine.
• Short chain fatty acid, like Octanoic acids can directly cross the mitochondrial membrane and does not require carnitine association or CPT-I enzyme.
• CPT-I is in turn inhibited by Malonyl-CoA.
• Thus, when there is high concentration of Malonyl-CoA, it acts as an inhibitor to enzyme CPT-I. As a result, long chain fatty acids, like Palmitic acid cannot be coupled to carnitine. So, it cannot enter the mitochondria for oxidation.
• The regulation of Malonyl-Co concentration is observed to be regulated by hormones insulin and glucagon.
• Thus, Malonyl-CoA will have little or no effect in oxidation of Octanoic acid, but may have inhibitory effect on Plmitic acid axidation.