Pyruvate, or its conjugate acid pyruvic acid, is important in many metabolic pathways. It can be created from glucose via glycolysis, it can be converted to carbohydrates or fatty acids, and can be used in fermentation as well. It is an energy supply in either the citric acid cycle or fermentation, depending on the oxygen present for the cells. In this pathway, pyruvic acid can be obtained from sources such as tyrosine metabolism. Pyruvic acid can then react with thiamine pyrophosphate, using pyruvate dehyderogenase as an enzyme, removing a carbon dioxide and forming 2-(a-hydroxyethyl)thiamine diphosphate. This then reacts with a protein N6-(lipoyl)lysine compound, again using pyruvate dehydrogenase as the enzyme, reforming thiamine pyrophosphate as well as S-acetyldihydrolipoamide-E. This then can be converted to and from acetyl-CoA by the addition of CoA with a dihydrolipoic transacetylase, which also forms protein N6-(dihydrolipoyl)lysine. This can also be converted to and from protein N6-(lipoyl)lysine by dihydrolipoyl dehydrogenase. Acetyl-CoA can interact with acetyl-CoA thiol esterase to add a water molecule and remove the CoA, forming acetic acid. Acetic acid can also be formed from acetylphosphate, which interacts with acylphosphatase to add a water molecule and remove the phosphate group. From here, acetic acid can interact with acetyl-CoA synthetase to form acetyl adenylate reversibly. Acetyl adenylate can also be formed directly from acetyl-CoA via the same acetyl-CoA synthetase enzyme. Acetyl-CoA can also interact with acetyl-CoA carboxylase to form malonyl-CoA, a compound which, along with acetyl-CoA, is used in fatty acid biosynthesis and elongation. Alternately, acetyl-CoA can interact with acetoacetyl-CoA thiolase, which takes two molecules of acetyl-CoA and combines them, removing one CoA and forming acetoacetyl-CoA in the mitochondria. Another pathway pyruvic acid can go through is its conversion to oxalacetic acid. Oxalacetic acid can then be converted to and from L-malic acid by malate dehydrogenase which adds a hydrogen ion to the oxalacetic acid. L-malic acid can then either interact with NAD-specific malic enzyme to be converted to and from pyruvic acid, or fumarate hydratase, converting it to and from fumaric acid, both of which occur in the mitochondria. Oxalacetic acid can also be converted to and from phosphoenolpyruvic acid by phosphoenolpyruvate carboxylase. This can then interact with pyruvate kinase, removing its phosphate group and adding it to ADP, forming both ATP and pyruvic acid. Pyruvic acid can also be formed in a pathway that starts with D-lactaldehyde. D-lactaldehyde can be converted to and from pyruvaldehyde by NADPH-glyoxylate reductase, which removes a hydrogen ion, forming a second carbonyl in the molecule. pyruvaldehyde can then be further converted to and from S-lactoylglutathione by lactoylglutathione lyase, which adds a glutathione to the pyruvaldehyde. Following this, S-lactoylglutathione enters the mitochondria and interacts with a hydroxyacylglutathione hydrolase which adds a water molecule and removes the glutathione, which is important in maintaining mitochondrial redox homeostasis. The D-lactic acid produced then can react with ferricytochrome c to form ferrocytochrome c and pyruvic acid, catalyzed by a lactic acid dehydrogenase, also in the mitochondria.

Pyruvate Metabolism References