Scholz T D, Koppenhafer S L, TenEyck C J, Schutte B C
Department of Pediatrics, University of Iowa, Iowa City 52242, USA.
J Mol Cell Cardiol. 1997 Jun;29(6):1605-13. doi: 10.1006/jmcc.1997.0394.
The alpha-glycerophosphate (alpha-GP) shuttle has been shown to play a role in reducing equivalent transfer in neonatal cardiac mitochondria. In adult heart mitochondria, alpha-GP shuttle activity is not detectable. The goals of the current study were to define the time course of the age-dependent decline in alpha-GP shuttle capacity and to identify the enzymatic step(s) of the alpha-GP shuttle which are regulated during development. Intact mitochondria were isolated from porcine hearts of various ages and assayed for alpha-GP shuttle capacity. By 5 weeks of age, alpha-GP shuttle capacity had decreased by nearly 39%. The cytosolic step of the shuttle, catalysed by cytosolic alpha-glycerophosphate dehydrogenase (c alpha-GPDH), demonstrated a significant increase between 0-2-day-old animals and adults. Partial cDNA clones of porcine c alpha-GPDH and mitochondrial alpha-glycerophosphate dehydrogenase (m alpha-GPDH) were prepared and used to quantitate expression of these genes. Using mRNA isolated from neonatal and adult porcine myocardium, expression of the c alpha-GPDH was unchanged, while expression of the m alpha-GPDH gene was present in neonatal but absent in adult myocardium. These results demonstrate a rapid postnatal decline in myocardial alpha-GP shuttle capacity which appears to be regulated by a decline in m alpha-GPDH gene expression.
α-甘油磷酸穿梭已被证明在新生儿心脏线粒体的还原当量转运中发挥作用。在成年心脏线粒体中，无法检测到α-甘油磷酸穿梭活性。本研究的目的是确定α-甘油磷酸穿梭能力随年龄下降的时间进程，并确定在发育过程中受到调控的α-甘油磷酸穿梭的酶促步骤。从不同年龄的猪心脏中分离出完整的线粒体，并测定其α-甘油磷酸穿梭能力。到5周龄时，α-甘油磷酸穿梭能力下降了近39%。穿梭的胞质步骤，由胞质α-甘油磷酸脱氢酶（cα-GPDH）催化，在0至2日龄动物和成年动物之间有显著增加。制备了猪cα-GPDH和线粒体α-甘油磷酸脱氢酶（mα-GPDH）的部分cDNA克隆，并用于定量这些基因的表达。使用从新生和成年猪心肌中分离的mRNA，cα-GPDH的表达没有变化，而mα-GPDH基因的表达在新生心肌中存在，但在成年心肌中不存在。这些结果表明，心肌α-甘油磷酸穿梭能力在出生后迅速下降，这似乎是由mα-GPDH基因表达的下降所调控的。
