How might excessive levels of phenylpyruvate interfere with pyruvate metabolism?
=> Pyruvate is transported into the mitochondria for oxidation; this transport involves a specific carrier protein. Phenylpyruvate inhibits the transport of pyruvate (but not acetate) into human red blood cells, and into rat liver and brain mitochondria. The results with rat tissue, supported by the results with human red blood cells, suggest the existence of a similar carrier in humans. They further suggest that this carrier would be specifically inhibited by phenylpyruvate in humans. Such inhibition would block much of the formation of acetyl CoA in the mitochondria, though some could be derived from fatty acid metabolism. The acetyl CoA is needed for TCA cycle turnover and is a key part of energy generation in the mitochondria. Thus a block of the entry of pyruvate into mitochondria would reduce the cell’s ability to generate energy.
