Role of the kidneys in the metabolism of plasma mevalonate. Studies in humans and in rhesus monkeys.

摘要: Abstract Studies were carried out in humans and rhesus monkeys to determine the role of kidneys metabolism circulating mevalonic acid (MVA). Following intravenous infusion [14C]MVA [3H]cholesterol, there was a rapid appearance [14C]squalene that exhibited significantly longer half-life than plasma or hepatic squalene. In man equilibration between newly synthesized cholesterol from MVA exogenously administered all tissues except kidneys, where specific activity ratio exogenous higher. Estimates quantitative intravenously infused radiolabeled monkey demonstrated 23% excreted urine, 67% metabolized (58% nonrenal 9% kidneys), 10% catabolized CO2 nonsteroid products. Measurements anephric uninephric patients demonstrate that, absence renal uptake MVA, achieve almost instantaneous equilibrium plasma; whereas control subjects with normal function, this required at least 21 d for two decay curves become parallel. These results suggest are solely responsible observed disequilibrium cholesterol; we due delayed release into compartment following MVA. The data document importance However, calculation significance pathway relation whole body indicates accounts approximately 0.1% daily turnover, alterations any form pathology would not result significant changes sterol synthesis rates. We urge caution use long-term kinetic studies because our show is necessarily isotopic tissue