Morris A A, Lascelles C V, Olpin S E, Lake B D, Leonard J V, Quant P A
Metabolic Unit, Institute of Child Health, London, United Kingdom.
Pediatr Res. 1998 Sep;44(3):392-6. doi: 10.1203/00006450-199809000-00021.
There are at least two isoenzymes of 3-hydroxy-3-methylglutaryl (HMG)-CoA synthase (EC 4.1.3.5) located in the mitochondrial matrix and the cytoplasm of hepatocytes, respectively. The mitochondrial enzyme is necessary for the synthesis of ketone bodies, which are important fuels during fasting. We report a child with a deficiency of this isoenzyme. He presented at 16 mo with hypoglycemia. There was no rise in ketone bodies during fasting or after a long chain fat load but there was a small rise after a leucine load. Measurement of beta-oxidation flux in fibroblasts was normal. Using antibodies specific for mitochondrial HMG-CoA synthase, no immunoreactive material could be detected on Western blotting. Total HMG-CoA synthase activity in liver homogenate was only slightly lower than in control samples. Presumably, as there was no mitochondrial HMG-CoA synthase enzyme protein, this activity arose from the cytoplasmic or other (e.g. peroxisomal) isoenzymes. With avoidance of fasting, our patient has had no problems since presentation and is developing normally at 4 y of age.
3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）合酶（EC 4.1.3.5）至少有两种同工酶，分别位于肝细胞的线粒体基质和细胞质中。线粒体酶是酮体合成所必需的，酮体是禁食期间的重要燃料。我们报告了一名该同工酶缺乏的儿童。他16个月大时出现低血糖。禁食期间或长链脂肪负荷后酮体没有升高，但亮氨酸负荷后有小幅升高。成纤维细胞中β-氧化通量的测量结果正常。使用针对线粒体HMG-CoA合酶的特异性抗体，在蛋白质印迹法上未检测到免疫反应性物质。肝匀浆中总HMG-CoA合酶活性仅略低于对照样品。据推测，由于不存在线粒体HMG-CoA合酶蛋白，这种活性来自细胞质或其他（如过氧化物酶体）同工酶。由于避免了禁食，我们的患者自发病以来没有出现问题，4岁时发育正常。
