Abstract

The enzymology and regulation of adrenal cortex steroidogenesis will be studied with particular emphasis on the role of the mitochondrial phospholipid membrane in the control of cytochrome P-450scc - dependent side chain cleavage of cholesterol. The enzymes adrenodoxin reductase, adrenodoxin, and cytochrome P-450 will be studied using Resonance Raman Spectroscopy, EPR using spin-labelled phospholipids and cholesterol, UV-visible absorbance spectrophotometry, and stopped flow spectrophotometry. The ACTH-control mechanism will be studied using cell cultures of an ACTH-responsive mouse adrenocortical cell line, and will include ACTH effects on adrenal phospholipid metabolism. Control by progesterone of 11Beta-hydroxylation has been observed, and will be studied in the purified enzyme system and in the cell cultures.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Modified Research Career Development Award (K04)
Project #
5K04AM001085-04
Application #
3071129
Study Section
Physical Biochemistry Study Section (PB)
Project Start
1982-07-01
Project End
1987-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
4
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Emory University
Department
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322

  Publications

Fowler Jr, W T; Lambeth, J D; Powell, G L (1988) Photoreactive cardiolipin analogues. Chem Phys Lipids 47:261-71
Lambeth, J D (1986) Cytochrome P-450scc a review of the specificity and properties of the cholesterol binding site. Endocr Res 12:371-92
Heyl, B L; Tyrrell, D J; Lambeth, J D (1986) Cytochrome P-450scc-substrate interactions. Role of the 3 beta- and side chain hydroxyls in binding to oxidized and reduced forms of the enzyme. J Biol Chem 261:2743-9
Nisimoto, Y; Wilson, E; Heyl, B L et al. (1986) NADH dehydrogenase from bovine neutrophil membranes. Purification and properties. J Biol Chem 261:285-90
Stevens, V L; Lambeth, J D; Merrill Jr, A H (1986) Use of cytochrome P-450scc to measure cholesterol-lipid interactions. Biochemistry 25:4287-92
Nisimoto, Y; Lambeth, J D (1985) NADPH-cytochrome P-450 reductase-cytochrome b5 interactions: crosslinking of the phospholipid vesicle-associated proteins by a water-soluble carbodiimide. Arch Biochem Biophys 241:386-96
Stevens, V L; Tribble, D L; Lambeth, J D (1985) Regulation of mitochondrial compartment volumes in rat adrenal cortex by ether stress. Arch Biochem Biophys 242:324-7
Lambeth, J D; Kriengsiri, S (1985) Cytochrome P-450scc-adrenodoxin interactions. Ionic effects on binding, and regulation of cytochrome reduction by bound steroid substrates. J Biol Chem 260:8810-6