PT  - JOURNAL ARTICLE
AU  - D. L. CINTI
AU  - J. B. SCHENKMAN
TI  - Hepatic Organelle Interaction
DP  - 1972 May 01
TA  - Molecular Pharmacology
PG  - 327--338
VI  - 8
IP  - 3
4099  - http://molpharm.aspetjournals.org/content/8/3/327.short
4100  - http://molpharm.aspetjournals.org/content/8/3/327.full
SO  - Mol Pharmacol1972 May 01; 8
AB  - A technique which permits the measurement of levels of mitochondrial and endoplasmic reticulum pigments in the hepatocyte, the examination of changes in the oxidation-reduction states of these pigments, and the study of interactons between the mitochondrial and endoplasmic reticulum electron transport chains is described. The content of cytochrome P-450 was about 30 nmoles/g of liver, wet weight. Based on the microsomal concentration of cytochrome P-450, the microsomal protein content ranged from 50 to 70 mg/g of liver. The total mitochondrial pigment concentration was 83 nmoles/g of liver, wet weight, and 1.16 nmoles/mg of mitochondrial protein. Based on these figures there were about 75 mg of mitochondrial protein per gram of liver. The rate of reduction of cytochrome P-450 in liver slices was also measured; the endogenous rate of reduction was 1.5-3.0 nmoles/g of liver per minute, and it increased to 4.5 nmoles/g/min in the presence of NADPH. The addition of 8 mM aminopyrine doubled the rate of reduction of cytochrome P-450 to 5.0-6.0 nmoles. When a Krebs cycle intermediate such as succinate was added in the presence of aminopyrine, a further doubling of the rate of reduction of cytochrome P-450 occurred (9.0-10.0 nmoles/g of liver per minute). The presence of succinate in the medium containing both aminopyrine and NADPH increased the P-450 reductase activity synergistically to 23 nmoles/g of liver per minute. These data indicate that the mitochondria may be a site of cellular control of drug biotransformation in the endoplasmic reticulum. ACKNOWLEDGMENT The authors express their thanks to Dr. Joan Higgins of the Department of Anatomy, Yale University, for the interpretation of the electron micrographs.