Number 26, 2005
Cardiovascular effects of exercise

Glossary

Gary D. Lopaschuk

Dichloroacetate
Dichloroacetate is a molecule that activates pyruvate dehydrogenase (PDH). PDH is the rate-limiting enzyme involved in glucose oxidation. In muscle cells, dichloroacetate activation of PDH results in an increase in glucose oxidation. In the heart, this activation of glucose oxidation has cardioprotective effects during and following ischemia.

Hexokinase
Hexokinase is an important enzyme that phosphorylates glucose to glucose-6-P in the cytoplasm of cells. This allows glucose to be further metabolized. The glucose-6-P can be used as a substrate for glycolysis, a substrate for glycogen synthesis, or as a substrate for the pentose phosphate pathway. However, all of these pathways require that hexokinase first phosphorylate glucose.

Long-chain 3-ketoacyl coenzyme A thiolase
3-ketoacyl-CoA-thiolase (3-KAT) is the last enzyme in the intramitochondrial pathway that is involved in the metabolism of fatty acids (fatty acid ß-oxidation). There are 3 different 3-KAT enzymes, with different affinities for long, medium or short chain fatty acids. Long-chain 3-KAT primarily acts on longer chain fatty acid intermediates. Long-chain 3-KAT inhibitors, such as trimetazidine, inhibit the activity of this enzyme, thereby inhibiting fatty acid oxidation. Recent interest has focused on 3-KAT inhibitors as a novel therapeutic approach to protecting the ischemic heart.

6-Phosphofructo-1-kinase
6-phosphofructo-1-kinase (PFK-1) is an enzyme that converts fructose 6-phosphate to fructose 1,6-bisphosphate. PFK-1 is the rate-limiting enzyme of glycolysis. As a result, regulation of PFK-1 is an important mechanism by which glycolysis is regulated.

Pyruvate dehydrogenase (PDH)
Pyruvate dehydrogenase (PDH) is an intramitochondrial complex that converts pyruvate (which primarily originates from glucose or lactate) into acetyl CoA. PDH is the rat-limiting enzyme for the mitochondrialk metabolism of carbohydrates. Maintaining mitochondrial glucose metabolism is an important therapeutic strategy to protect the ischemic heart. Therefore, activating PDH is a potential therapeutic approach to treating heart disease.