Metabolism of C14 mevalonate by adult and fetal arteries.
The metabolism of mevalonate by the arterial wall was evaluated in fetal and adult maternal arteries of the New Zealand white rabbit. Freshly minced tissue from umbilical arteries, fetal aortas and adult maternal aortas was incubated in oxygenated Krebs Henseleit bicarbonate buffer at 37 degrees C in the presence of 5-14C-mevalonate or 5-14C-3-hydroxy-3-methylglutaryl-Coenzyme A (HMG CoA). After incubation, the arterial tissue lipids were extracted and total cholesterol and free fatty acids were purified by thin layer chromatography and assayed for 14C by liquid scintillation spectrometry and analyzed chemically. The conversion of labeled HMG CoA or mevalonate to cholesterol in fetal aorta was 15 fold greater than in maternal aorta and 5-10 fold greater than in fetal umbilical artery. In addition some 14C from HMG CoA became incorporated into palmitate, stearate and oleate while 14C from mevalonate appeared in palmitate and stearate in trace amounts. Similarly, conversion of label from both precursors to 14CO2 was greatest in fetal aorta followed by umbilical artery and maternal aorta of the term pregnant rabbit. Of particular interest was the observation of enhanced (3.5 fold) conversion of label from mevalonate to 14CO2 by maternal aortas at mid-gestation compared to aortas of late-term gestation. These results are consistent with the explanation that while mevalonate clearly serves as a precursor for cholesterol synthesis in arterial tissue, a finite degree of exclusion from the main stream sterol pathway also occurs. This "shunt" pathway may involve oxidation directly to CO2 or indirectly by way of fatty acids. The level of activity through this exclusion pathway in arterial tissue appears to be under physiologic control during pregnancy since a 3.5 fold increase in conversion to 14CO2 occurred in aortas obtained in midgestation compared to those obtained at term gestation.
D000214:Acyl Coenzyme A / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic / Q000196:embryology / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000378:metabolism*; D005865:Gestational Age; D008798:Mevalonic Acid / Q000378:metabolism*; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism; D011247:Pregnancy; D011817:Rabbits; D013229:Stearic Acids / Q000378:metabolism; D014469:Umbilical Arteries / Q000378:metabolism*
D000214:Acyl Coenzyme A; D009829:Oleic Acids; D010169:Palmitic Acids; D013229:Stearic Acids; C008047:3-hydroxy-3-methylglutaryl-coenzyme A; D019301:Oleic Acid; D019308:Palmitic Acid; C031183:stearic acid; D002784:Cholesterol; D008798:Mevalonic Acid