Number 23, 2004
Hibernation preconditioning

Glossary

Gary D. Lopaschuk

Acetyl CoA carboxylase (ACC) and malonyl CoA decarboxylase (MCD)
ACC and MCD are two enzymes that control malonyl CoA levels in a number of different types of cells, particularly heart and skeletal muscle. ACC synthesizes malonyl CoA from acetyl CoA, while MCD degrades malonyl CoA back to acetyl CoA. These are important reactions, since malonyl CoA is a potent inhibitor of mitochondrial fatty acid uptake, and therefore an important regulator of muscle fatty acid oxidation.

AMP-activated protein kinase (AMPK)
AMPK is a kinase that is activated in cells during times of metabolic stress. As the name implies, it is activated by AMP. AMPK phosphorylates many enzymes and, in general, inhibit enzymes involved in energy consuming anabolic process, while activating enzymes involved in catabolic energy-producing processes.

CrCl level
CrCl is the abbreviation for creatinine clearance. Measurement of creatinine clearance rates is used to assess kidney function.

Glut1 and Glut4
Glut1 and Glut4 are glucose transporters that facilitate the transport of glucose across the cell membrane. They are the two main glucose transporters found in heart and skeletal muscle. In the presence of insulin, Glut4 is translocated from the interior of the cell to the cell membrane, thereby resulting in an increase in muscle glucose uptake.

Glycosylation end products
Glycosylation is the process of adding oligosaccaride moieties to proteins or other molecules. In diabetes, chronically high glucose levels will increase the level of protein glycosylation. Therefore, by measuring glycosylation end products, the longer term degree of glucose control can be determined.

Glycolysis
Glycolysis is the first part of the pathway by which glucose is metabolized in cells. It is a highly regulated pathway that converts glucose to pyruvate. In the process of doing this, two ATP molecules are produced. This occurs without the requirement for oxygen.

Kinase
A kinase is an enzyme that phosphorylates (i.e. adds a phosphate group) to other proteins and/or itself. Kinases are very important enzymes involved in numerous cell signalling processes.

Long-chain 3-ketoacyl coenzyme A thiolase (LC 3-KAT)
LC 3-KAT is the last enzyme in the fatty acid β-oxidation pathway. It functions to produce acetyl CoA from long chain fatty acids, which results in the two carbon shortening of the fatty acids. LC 3-KAT is the enzyme that is inhibited by the anti-anginal agent, trimetazidine. Inhibition of LC 3KAT results in a decrease in fatty acid oxidaton and a concomitant increase in glucose oxidation in the heart.

Myoglobin
Myoglobin is an important intracellular oxygen binding hemoprotein found in abundance in heart and skeletal muscle. Myoglobin not only provides oxygen for mitochondrial oxidative metabolism, it also buffers intracellular oxygen during changes in mitochondrial oxygen demand.

Na/K-ATPase and the SR-Ca++-ATPase
Na/K-ATPase and the SR-Ca⁺⁺-ATPase are two ion pumps that are involved in the transport of ions across membranes. They usually pump these ions against a concentration gradient, and therefore energy is required, which is provided by the hydrolysis of ATP, the main energy currency in cells (hence the name ATPases). Na/K-ATPase pumps Na⁺ out of cells, while simultaneously pumping K⁺ into cells. The SR -Ca⁺⁺-ATPase pumps Ca⁺⁺ from the cytoplasm into sarcoplasmic reticulum vesicles. In muscle, this results in a lowering of cytoplasmic calcium and a relaxation of the muscle.

Phosphofructokinase
Phosphofructokinase (PFK) is the rate-limiting enzyme involved in the glycolytic pathway. It is a highly regulated enzyme that converts fructose 6-phosphate to fructose 1,6 bisphosphate. Activation of PFK results in an activation of glycolysis, while inhibition of PFK results in an inhibition of glycolysis.

Pyruvate dehydrogenase complex (PDH)
The PDH complex is composed of a number of enzymes whose function is to convert pyruvate (which mainly originates from glycolysis or lactate dehydrogenase) and CoA into acetyl CoA. In the process, NAD+ is reduced to NADH. The acetyl CoA produced enters the tricarboxylic acid cycle where it is further metabolized, whereas NADH is used as an electron donor by the mitochondrial electron transport chain. PDH is the rate-limiting step in glucose oxidation.