McKenna Mary C, Waagepetersen Helle S, Schousboe Arne, Sonnewald Ursula
Department of Pediatrics, University of Maryland School of Medicine, 655 West Baltimore Street, Room 10-031, Baltimore, MD 21201-1509, USA.
Biochem Pharmacol. 2006 Feb 14;71(4):399-407. doi: 10.1016/j.bcp.2005.10.011. Epub 2005 Dec 20.
The malate-aspartate shuttle and the glycerol phosphate shuttle act to transfer reducing equivalents from NADH in the cytosol to the mitochondria since the inner mitochondrial membrane is impermeable to NADH and NAD+. This transfer of reducing equivalents is essential for maintaining a favorable NAD+/NADH ratio required for the oxidative metabolism of glucose and synthesis of neurotransmitters in brain. There is evidence that both the malate-aspartate shuttle and glycerol phosphate shuttle function in brain; however, there is controversy about the relative importance and cellular localization of these shuttles. The malate-aspartate shuttle is considered the most important shuttle in brain. It is particularly important in neurons and may be extremely low, or even non-existent in brain astrocytes. Several studies provide evidence of glycerol phosphate shuttle activity in brain cells; however, the activity of this shuttle in brain has been questioned. A number of pharmacological tools, including aminooxyacetic acid, beta-methyleneaspartate, phenylsuccinate, and 3-nitropropionic acid, have been used to inhibit the four enzymes and two carrier proteins that participate in the malate-aspartate shuttle. Although no drugs completely inhibit the glycerol phosphate shuttle, evidence for the existence of this shuttle is provided by studies using drugs to inhibit the malate-aspartate shuttle. This report evaluates the evidence for each shuttle in brain cells and the drugs that can be used as pharmacological tools to study these shuttles.
苹果酸 - 天冬氨酸穿梭和磷酸甘油穿梭的作用是将胞质溶胶中NADH的还原当量转运至线粒体，因为线粒体内膜对NADH和NAD +是不可渗透的。这种还原当量的转运对于维持大脑中葡萄糖氧化代谢和神经递质合成所需的有利NAD + / NADH比率至关重要。有证据表明苹果酸 - 天冬氨酸穿梭和磷酸甘油穿梭在大脑中均起作用；然而，关于这些穿梭的相对重要性和细胞定位存在争议。苹果酸 - 天冬氨酸穿梭被认为是大脑中最重要的穿梭。它在神经元中尤为重要，而在脑星形胶质细胞中可能极低，甚至不存在。多项研究提供了脑细胞中磷酸甘油穿梭活性的证据；然而，该穿梭在大脑中的活性受到质疑。一些药理学工具，包括氨基氧乙酸、β - 亚甲基天冬氨酸、苯基琥珀酸和3 - 硝基丙酸，已被用于抑制参与苹果酸 - 天冬氨酸穿梭的四种酶和两种载体蛋白。虽然没有药物能完全抑制磷酸甘油穿梭，但使用抑制苹果酸 - 天冬氨酸穿梭的药物进行的研究为该穿梭的存在提供了证据。本报告评估了脑细胞中每种穿梭的证据以及可作为研究这些穿梭的药理学工具的药物。
