Moore K H, Koen A E, Hull F E
J Clin Invest. 1982 Feb;69(2):377-83. doi: 10.1172/jci110461.
beta-Hydroxymyristate, -palmitate, and -stearate were produced by and accumulated in isolated rabbit heart when perfused ischemically for 2-10 min by the nonrecirculating langendorff technique with 0.75 mM palmitate and 0.16 mM albumin. Tissue fractionation into mitochondria and cytosol showed that by 2 min of ischemia 44% of beta-hydroxypalmitate and 38% beta-hydroxystearate was located in the cytosol; this percentage increased to greater than 50% by 5 min of ischemia. Lipid fractionation studies showed that by 10 min these two beta-hydroxy fatty acids were distributed approximately as 60% acylcarnitine, 20% acyl-coenzyme A (CoA), and 20% free fatty acids. All three chemical forms of beta-hydroxypalmitate were found in both the mitochondria and the cytosol. After 10 min of ischemia beta-hydroxypalmitoyl-CoA and beta-hydroxystearoyl-CoA constituted at least 16% of the incremental long-chain acyl-CoA, whereas beta-hydroxypalmitoylcarnitine and b-hydroxystearoylcarnitine constituted 8% of the incremental long-chain acylcarnitine. These data suggests that myocardial beta-hydroxyacyl-CoA oxidation is limited during ischemia. Substrate accumulates and is transferred to the cytosol where it accumulates primarily as beta-hydroxyacylcarnitine.
在采用非循环Langendorff技术,用0.75 mM棕榈酸盐和0.16 mM白蛋白对离体兔心脏进行2 - 10分钟的缺血灌注时,会产生并积累β-羟基肉豆蔻酸盐、β-羟基棕榈酸盐和β-羟基硬脂酸盐。将组织分离为线粒体和胞浆后发现,缺血2分钟时,44%的β-羟基棕榈酸盐和38%的β-羟基硬脂酸盐位于胞浆中;缺血5分钟时,这一比例增加到50%以上。脂质分离研究表明,到10分钟时,这两种β-羟基脂肪酸的分布大致为60%的酰基肉碱、20%的酰基辅酶A(CoA)和20%的游离脂肪酸。β-羟基棕榈酸盐的所有三种化学形式在线粒体和胞浆中均有发现。缺血10分钟后,β-羟基棕榈酰-CoA和β-羟基硬脂酰-CoA至少占增量长链酰基辅酶A的16%,而β-羟基棕榈酰肉碱和β-羟基硬脂酰肉碱占增量长链酰基肉碱的8%。这些数据表明,缺血期间心肌β-羟基酰基辅酶A氧化受到限制。底物积累并转移到胞浆中,在胞浆中它主要以β-羟基酰基肉碱的形式积累。