Glossary

Gary Lopaschuk and William Stanley

3-hydroxyacyl-CoA dehydrogenase
3-hydroxyacyl-CoA dehydrogenase is the third enzyme in the intramitochondrial pathway that is involved in the metabolism of fatty acids (fatty acid b-oxidation). Recent interest has focused on inhibition of fatty acid oxidation as a way to protect the ischemic heart.

Carnitine palmitoyl transferase-1 (CPT-1) and carnitine-acylcarnitine translocase
Carnitine palmitoyltransferase-1 (CPT-1) and carnitine-acylcarnitine translocase are two important enzymes involved in the mitochondrial uptake of fatty acids. CPT-1 is the rate-limiting enzyme involved in the uptake of fatty acids into the mitochondria. It converts fatty acyl-CoA to fatty acylcarnitine, which is then transported into the mitochondria where it is further metabolized. CPT-1 is a highly regulated enzyme that prevents excess amounts of fatty acids from being taken up into the mitochondria. Carnitine-acylcarnitine translocase is the enzyme responsible for translocating acylcarnitine across the mitochondrial membrane in exchange for carnitine.

Cytochrome c oxidase
Cytochrome c oxidase is a mitochondrial enzyme that has an important role in the electron transport function of mitochondrial respiration. The oxidation of cytochrome c by cytochrome c oxidase is one of the steps that results in electron transport via this pathway. The electron transport chain transfers electrons through a number of different enzyme complexes which catalyze the pumping of protons out of the mitochondrial matrix. These protons can then pass back into the mitochondria via an enzyme called ATP synthase. The downhill electrochemical gradient of this process produces energy that results in the production of ATP from ADP. ATP is a form of chemical energy used in most cellular processes requiring energy.
Endothelial nitric oxide synthase
Nitric oxide synthase is the enzyme responsible for synthesizing nitric oxide. Nitric oxide has received considerable research attention, since it is not only a vasodilator but is also important in numerous other processes, including apoptosis. Nitric oxide synthase present in endothelial cells is an important source of nitric oxide.

Fatty acid binding protein (FABP)
Fatty acid binding protein is an abundant cytoplasmic protein (especially cardiac cells) that binds fatty acids and facilitates their transport to intracellular compartments. One of its functions is to transport fatty acids from the cell membrane to the mitochondria.

Fatty acid translocase (FAT)
Fatty acid translocase (FAT) is a protein found in the plasma membrane of many cells and is thought to be involved in the transport of fatty acids across the membrane and into the cell. It has been suggested that FAT is responsible for a significant portion of fatty acid uptake into the cardiac cell.

GLUT4
GLUT4 is a protein that transports glucose across cell membranes. In insulin-responsive tissues (such as the heart), insulin will cause GLUT4 to be translocated from inside the cell to the plasma membrane, thereby stimulating glucose uptake.

Myosin heavy chain
Myosin heavy chain is a key component of the contractile apparatus of muscle cells and comprises the thick filament of muscle fibers. Sliding of myosin by actin (another major structure of contractile proteins) is an important step in muscle contraction.

Oxygen radical scavenger enzymes
Oxygen-derived free radicals are highly reactive compounds that can react with and damage cellular components (lipid membranes, protein, and DNA/RNA). In order to protect the cell from these oxygen-derived free radicals, cells have a number of different oxygen radical scavenger enzymes that are used to neutralize these free radicals.

Peroxisome proliferator-activated receptor-a (PPARa)
Peroxisome proliferator-activated receptor-a (PPARa) is a nuclear receptor involved in transcriptional regulation of proteins. PPARa has many functions, including regulating enzymes involved in the control of fatty acid oxidation in the heart.

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 rate-limiting enzyme for the mitochondrial 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 ischemic heart disease.

Strain measured by MRI
Magnetic resonance imaging is a sophisticated technique that produces high-quality images of the body. Newer MRI techniques allow for high resolution of the heart structure and chamber dimensions. Strain measured by MRI is an approach to investigate heart function and wall tension.