The kinetic basis of threshold effects observed in mitochondrial diseases: a systemic approach

Biochem J. 1994 Aug 15;302 ( Pt 1)(Pt 1):171-4. doi: 10.1042/bj3020171.

Abstract

Threshold effects in the expression of metabolic diseases have often been observed in mitochondrial pathologies, i.e. the clinical demonstration of the disease appears only when the activity of a step has been reduced to a rather low level. We show experimentally that an inhibition of cytochrome c oxidase activity by cyanide, simulating a defect in this step, leads to a decrease in mitochondrial respiration which then exhibits a threshold behaviour similar to that observed in mitochondrial diseases. We discuss this behaviour in terms of metabolic control theory and construct a mathematical model simulating this behaviour.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Electron Transport Complex IV / antagonists & inhibitors
  • Electron Transport Complex IV / metabolism
  • In Vitro Techniques
  • Kinetics
  • Metabolic Diseases / metabolism*
  • Mitochondria, Muscle / enzymology*
  • Potassium Cyanide / pharmacology
  • Rats

Substances

  • Electron Transport Complex IV
  • Potassium Cyanide