Thermal instability in the endoplasmic reticulum of the rat hepatocyte.
The rates of heat denaturation of a protein component of endoplasmic reticulum, NADPH cytochrome c reductase, measured in the temperature range of 37-47 degrees C, show that this protein is highly unstable in the range of temperatures used in clinical hyperthermia. The rate of enzyme inactivation increases some 20-fold as the temperature increases from 37 degrees C to 45 degrees C. The enzyme has an in vitro half-life of only 7 h due to thermal inactivation at 37 degrees C. This suggests a general scheme for the physiological degradation pathway of intracellular proteins in which the first step is rapid thermal denaturation of the molecule followed by a second and slower step of proteolytic degradation. The rapid physiological turnover of intracellular proteins may be an unavoidable cost of maintaining metabolic precision in the presence of thermal noise at normal body temperature.
D000818:Animals; D004355:Drug Stability; D004721:Endoplasmic Reticulum / Q000648:ultrastructure*; D005334:Fever; D006358:Hot Temperature; D008099:Liver / Q000648:ultrastructure*; D008297:Male; D008854:Microscopy, Electron; D009251:NADPH-Ferrihemoprotein Reductase; D011489:Protein Denaturation; D051381:Rats; D011919:Rats, Inbred Strains
D009251:NADPH-Ferrihemoprotein Reductase