Number 27, 2005
Metabolic approach in heart failure

Glossary

Gary D. Lopaschuk

Creatine/phosphocreatine
Phosphocreatine is a chemical storage form of energy in cells. In times of increased energy demand, the high energy phosphate on phosphocreatine can be transferred to adenosine diphosphate (ADP) to form adenosine triphosphate (ATP) and creatine. ATP is then used by enzymes in energy requiring cellular processes. In times of low energy demand, the reverse reaction occurs, with creatine kinase catalyzing the formation of phosphocreatine and ADP from ATP and creatine. A creatine and phosphocreatine shuttle system is important in the transfer of high energy phosphates from mitochondria to the cytoplasm.

Peroxisome proliferative activated receptor gamma (PPAR-?) and PPAR-? coactivator 1a
Peroxisomal proliferators-activated receptors are nuclear receptors involved in the transcriptional regulation of proteins. One of these nuclear receptors is PPAR-?, which modifies the expression of a number of proteins, including those involved in insulin sensitivity and lipid metabolism. Activation of PPAR-? is a therapeutic approach to treating diabetes, which may in part be due lowering blood fatty acid levels, secondary to decreasing fatty acid release from adipose tissue. In the nucleus, a complex of proteins is involved in the regulation of PPAR mediated transcription. One of these proteins is peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1alpha). PGC-1-alpha is a transcriptional coactivator that plays a role in mitochondrial biogenesis and energy metabolism, and has been implicated in insulin release by beta cells and in insulin resistance. It is predominantly expressed in the kidney, heart, liver and skeletal muscle tissues.

Uncoupling protein
Uncoupling proteins (UCP) are proteins that are present in the inner mitochondrial membrane of cells that dissipate the proton gradient across this membrane. As a result of this action, mitochondrial respiration produces heat instead of ATP. Heart and skeletal muscle contain two isoforms of UCPs, UCP2 and UCP3. The exact function of these UCP's is not clear, but they may be involved in decreasing reactive oxygen species production by the mitochondria or transporting excess fatty acids out of the mitochondria. The expression of UCPs in the mitochondria is increased in muscle exposed to high fats.

GLUT-4
GLUT-4 is a protein that transports glucose across cell membranes. In insulin-responsive tissues (such as the heart), insulin will cause GLUT-4 to be translocated from inside the cell to the plasma membrane, thereby stimulating glucose uptake.