Elsevier

Metabolism

Volume 20, Issue 2, February 1971, Pages 187-199
Metabolism

Influence of hepatic microsomal mixed function oxidation reactions on cellular metabolic control

https://doi.org/10.1016/0026-0495(71)90091-6Get rights and content

Abstract

From the spectrophotometric observation of pigments, especially cytochrome P-450, in whole liver slices, and correlative studies using isolated endoplasmic reticulum particles, oxidative reactions occurring in the microsomal fraction are suggested as possible significant contributions to liver cell metabolism. The requirement of this system for TPNH and the synergistic involvement of DPNH could markedly affect the cytosol concentration and subsequent oxidized: reduced ratio of these pyridine nucleotides. The involvement of cytochrome b5 in the oxidative reaction, the necessity of enzymes transferring reducing equivalents from the reduced pyridine nucleotides to both cytochromes b5 and P-450 and mercurial inhibition studies demonstrating autonomy of the units catalyzing the microsomal TPNH supported mixed-function oxidation reactions aid, considerably, our understanding of the organization of this important enzymic activity within the endoplasmic reticulum of the liver.

References (19)

There are more references available in the full text version of this article.

Cited by (107)

  • Roles of cytochrome P450 enzymes in pharmacology and toxicology: Past, present, and future

    2022, Advances in Pharmacology
    Citation Excerpt :

    Although the mitochondrial P450s clearly have important roles in the metabolism of steroids and vitamins (Table 1) (Guengerich, 2015), in some cases they can also be involved in the metabolism of drugs (Zhang et al., 2012) and other chemicals. In mammalian liver the ratio of total P450 to POR has long been known to be 10–20:1 (Estabrook, Franklin, Cohen, Shigamatzu, & Hildebrandt, 1971). The concentrations of several P450s in human liver have been estimated using immunochemical (Shimada, Yamazaki, Mimura, Inui, & Guengerich, 1994) and, more recently, mass spectrometry proteomic approaches (Achour, Al Feteisi, Lanucara, Rostami-Hodjegan, & Barber, 2017).

  • Molecular mechanism of metabolic NAD(P)H-dependent electron-transfer systems: The role of redox cofactors

    2019, Biochimica et Biophysica Acta - Bioenergetics
    Citation Excerpt :

    Thus, an possible X-shaped contact model for the cyt P450 reductase-cyt P450 complex is shown in Fig. 9. Taken together, the concentration of cyt P450 reductase in the ER membranes has been estimated to be 1/10–1/40 of the total cyt P450s [166,167], indicating that a single cyt P450 reductase must interact with 50 microsomal cyt P450s. It is likely that the interactions between cyt P450 reductase and cyt P450s are relatively weak, including interactions between the soluble domains and their anchors.

  • NADPH P450 oxidoreductase: Structure, function, and pathology of diseases

    2013, Pharmacology and Therapeutics
    Citation Excerpt :

    In the lipid reconstituted in vitro systems P450 proteins form a complex with POR with an apparent Km of 0.2 μM (Davydov et al., 1996; Guengerich & Johnson, 1997; Backes & Kelley, 2003). P450 content in most tissues is about 5–10 fold higher than POR (Estabrook et al., 1971; Shephard et al., 1983; Shephard et al., 1992). Chemical agents have been shown to alter the POR:P450 ratio and phenobarbital treatment has been reported to change the POR:P450 ratio to 1:30.

  • Metabolic Defenses against Plant Allelochemicals

    2012, Herbivores: Their Interactions with Secondary Plant Metabolites Ecological and Evolutionary Processes: Second Edition
View all citing articles on Scopus

Supported in part by USPH Research Grant 5 P11 GM 16488

View full text