If de novo fatty acid synthesis is active would you expect malic enzyme to be active...

If de novo fatty acid synthesis is active would you expect malic enzyme to be active or not? Please explain.

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Expert Solution

Yes, during denovo fatty acid synthesis malic enzyme or malate dehydrogenase will be active because it plays an important role in the Acetyl coenzyme A shuttle system / citrate malate shuttle system and for the conversion malate to oxalo acetate.

Fatty acid biosynthesis takes place in the cytoplasm of the cell. For fatty acid biosynthesis, Acetyl coA is needed, which is produced from pyruvate by end of glycolysis When the pyruvate enters in to mitocondrial matrix, it gets converted to Acetyl coA. This Acetyl coA should be transported back to cytoplasm passing the barrier which is the mitocondrial membrane for the fatty acid synthesis. This transport is facilitated by the citrate- malate shuttle system.

The inner mitociondrial membrane acts as chemical barrier for the transport of AcetylcoA because it is only selectively permeable to O2, CO2, water and certain molecules. Other molecules are not able to cross this barrier without a carrier protein. So the Acetyl coA which is in the matrix will combine with the oxaloaetate to form citrate, which is calalyzed by enzyme citrate synthase. This citrate is able to cross the inner and outer membrane of mitochondria. Once this citrate reaches the cytosol, it reacts with cytosolic coA in presence of ATP and get cleaved down into acetyl coA and oxaloacetate, which is catalysed by citrate lyase. This acetyl coA produced will be used for fatty acid biosynthesis in cytoplasm.

The oxaloacetate formed in cytoplasm, should get back to the matrix crossing the mitocondrial membrane, which is not possible. So it gets converted to malate with help of a reducing agent NADH and malate dehydrogenase/malic enzyme. Malate is now able to cross the membrane and reaches the matrix where it gets oxidized back oxaleacatate with help of NAD+ and malic acid/malate dehydrogenase. So here an exchange method happend ,a citrate molecule is exchanged for a malate. In this way the shuttle continues in a cyclic manner for fatty acid synthesis.

gladiator answered 1 year ago

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