|Farrell Harold M|
|Reeves Henry C|
Submitted to: Archives Of Biochemistry and Biophysics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/24/1995
Publication Date: N/A
Citation: N/A Interpretive Summary: It has long been known that there is a strong link between the amount of fat and the amount of protein produced in cow's milk. By breaking this link, it may be possible to alter favorably the ratio of fat to protein in cows' milk. Currently the reasons for this strong link are unknown. We have studied the interrelationships between various compartments of the udder of the cow which produce fat and protein. In this work we have discovered that an intermediate in the manufacture of fat can slow up the synthesis of fat by binding to one of the enzymes necessary to fat production in the udder. The analysis of the test tube data suggest that this fat-enzyme-complex could in turn limit protein production as well. Understanding these metabolic interrelationships could lead to a biochemical intervention in the stimulation of protein production by the dairy cow.
Technical Abstract: The cytosolic form of NADP+:isocitrate dehydrogenase, a primary source of the NADPH required for de novo fatty acid synthesis in lactating bovine mammary gland, is inhibited by palmitoyl CoA. A analysis of the kinetic data suggested partial inhibition through binding to sites with an average dissociation constant of 3.3 micromoles, followed by binding to sites with an average dissociation constant of 294 micromoles, which increased the percent inhibition. Examination of the effect of acyl chain length demonstrated that only long chain CoA's with carbon numbers greater than 14 have this dual effect on kinetics. Stearoyl CoA completely inhibited the enzyme, other C18 acyl group produced varying effects depending on the degree of unsaturation and cis-trans isomerism. Concentration ranges observed for these transitions are compatible with physiological conditions. This suggests that complexes of acyl -CoA's and NADP+: isocitrate dehydrogenase, could be related to cytoplasmic events in the synthesis and secretion of lipid and possibly protein, since palmitoyl CoA is known to promote secretory processes through acylation reactions which lead to vesicle fusion.