Arterial metabolism in primates.
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Biomedical subjects
Publications and source records attributed to O W Portman.
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In order to explain why squirrel monkeys on some experimental diets develop cholesterol gallstones, we made a number of measurements on bile acid kinetics and on bile secretion and composition. The pool size of cholic acid was much greater in monkeys on a commercial diet than in any group on a semipurified diet. It was also greater in squirrel monkeys on a lithogenic diet but without gallstones than in monkeys from the same diet group with gallstones. The half-lives of cholic acid tended to be proportional to pool size, and absolute rates of cholic acid synthesis were, therefore, not much affected by diet. Diet did not affect the pool sizes and half-lives of chenodeoxycholic acid as much as those of cholic acid. Dietary cholesterol increased concentrations of cholesterol relative to bile acids and phospholipids in hepatic bile as well as absolute secretory rates of all three components. Interruption of the enterohepatic circulation of bile in fasted monkeys with gallstones resulted in a more rapid and marked increase in the relative cholesterol concentration and decline in the absolute concentration of bile acids in hepatic bile than occurred for monkeys without gallstones. This was due to the low proportion of the bile acid pool outside the gallbladder and the low rate of new bile acid synthesis of the monkeys with gallstones during fasting.
We studied the metabolism of different classes of lipoprotein in squirrel monkeys and rabbits. Lipoproteins were labeled in vivo in donor animals with (3H)leucine and (3H)cholesterol. The rate of disappearance from plasma of recipient squirrel monkeys of the protein moiety of the very low density lipoproteins was rapid, that of high density lipoproteins slow, and the rate for low density lipoproteins was intermediate. The fractional turnover of the apoprotein of low density lipoproteins was slightly reduced in hyperlipidemic monkeys, but the absolute rates of synthesis and catabolism were increased. Hyperdipidemia in rabbits resulted in a dramatic reduction in the fractional catabolic rate of low density lipoprotein apoprotein. Hyperlipidemia in the donors of biosynthetic low density lipoproteins also influenced the rates of catabolism in rabbits. We showed the cycloheximide that although there was recycling of (3H)leucine into other proteins, the reutilization of leucine from low density lipoproteins for nascent low density lipoproteins was not significant. In most tissues the ratio of cholesterol:protein radioactivity was much greater than that for plasma 24 h after administration of labeled low density lipoproteins, but the ratios for aortic intima plus inner media and for plasma low density lipoproteins were similar. The presence of atherosclerosis resulted in a large increase in the apparent uptake of low density lipoproteins by the aortas of rabbits and monkeys.
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