Structure-function relationships of various steroids relative to lipid metabolism in human blood cells

• Published in: Biochemical medicine Vol. 6; no. 6; pp. 483 - 494
• Main Authors: Duboff, G.S., Hennes, A.R., Awai, R., Hammerstrand, K.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.1972
• Subjects: Acetates - metabolism; Adult; Androstanes - pharmacology; Androstenes - pharmacology; Blood Cells - metabolism; Blood Platelets - metabolism; Carbon Isotopes; Cholesterol - blood; Erythrocytes - metabolism; Esters - blood; Fatty Acids - blood; Fatty Acids, Nonesterified - blood; Female; Glycerides - blood; Humans; Ketosteroids - pharmacology; Leukocytes - metabolism; Lipids - blood; Male; Middle Aged; Norethynodrel - pharmacology; Phospholipids - blood; Pregnanes - pharmacology; Pregnenes - pharmacology; Steroids - pharmacology; Sterols - blood; Structure-Activity Relationship
• ISSN: 0006-2944; 1557-7996
• DOI: 10.1016/0006-2944(72)90001-4

1. 1. 1- 14C-Acetate is incorporated into fatty acids by normal human platelets, leucocytes and erythrocytes. Gas-chromatographic separation of individual fatty acids revealed a consistent characteristic pattern of distribution of the isotopes. The radiocarbon was incorporated into short chain acids to a greater extent than into long chain acids in the time period studied. 2. 2. Addition of small amounts of ketosteroids to the incubation system changed this, resulting in a marked decrease in short chain incorporation and a significant increase in long chain fatty acid incorporation particularly in unsaturated equivalents. 3. 3. Platelets in isologous plasma, and as whole blood from women on long-term use of the oral contraceptive (Enovid) when incubated with the labeled acetate demonstrated the same remarkable changes in the pattern of uptake of radiocarbon into FA as that for the in vitro addition of the drug. 4. 4. It is adduced from the experimental evidence that a stereochemical, nonhormonal property of the steroids involved is the basis for the deviation in the formation and turnover of fatty acids. 5. 5. In vitro addition of malate and oxaloacetate to the steroid containing incubates resulted in complete “normalization” of incorporation of the radiocarbon by the cells into fatty acids, thus indicating that the steroidal agents may enter the fatty acid biosynthetic pathway at an early step, probably intervening directly on the pivotal decarboxylic acid-malonyl-CoA- and/or chain elongation cytoplasmic, mitochondrial and microsomal enzyme-coenzyme complex.