Downie M M T, Kealey T
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital, Box 232, Hills Road, Cambridge CB2 2QR, UK.
Br J Dermatol. 2004 Aug;151(2):320-7. doi: 10.1111/j.1365-2133.2004.06004.x.
The skin and its appendages support aerobic glycolytic and glutaminolytic metabolism. Their major fuels are glucose and glutamine, which are, however, largely catabolized anaerobically.
For the human sebaceous gland it has been reported that glucose, lactate and acetate provide good lipogenic substrates but that glutamine does not. Therefore, we have investigated the intermediary metabolism in vitro of freshly isolated human sebaceous glands to determine if their metabolism of glutamine is anomalous relative to the rest of the skin.
Glycolytic rate, glucose and glutamine oxidation, and glucose metabolism by the pentose phosphate pathway were determined in freshly isolated human chest sebaceous glands. Further, sebaceous intermediary metabolites were analysed using spectrophotometry and high-performance liquid chromatography. Moreover, glands were maintained in vitro as whole organs to investigate the effects of precursors and inhibitors of polyamine synthesis on rates and patterns of lipogenesis and DNA synthesis.
We confirm that the human sebaceous gland is a glycolytic and glutaminolytic tissue. Glucose is mainly converted to lactate, with only 6% of glucose being oxidized to CO(2). Glutamine is largely converted to glutamate, alanine, serine, glycine, aspartate, threonine, lactate and ammonia, with only 12% being oxidized. We have also shown that exogenous glutamine is required for cellular proliferation and lipogenesis by human sebaceous glands. However, in its absence spermidine could fully restore rates of DNA synthesis and lipogenesis.
Although glutamine is a poor substrate for sebaceous lipogenesis, this cannot be attributed to its lack of catabolism. We have shown that glutamine is an essential fuel, but that it can be replaced by exogenous spermidine. Therefore, we suggest that in sebocytes both glutamine and spermidine may act as essential purine and pyrimidine precursors.
皮肤及其附属器支持有氧糖酵解和谷氨酰胺分解代谢。它们的主要燃料是葡萄糖和谷氨酰胺,然而,这些燃料在很大程度上是通过无氧分解代谢的。
据报道,对于人类皮脂腺而言,葡萄糖、乳酸和乙酸盐是良好的脂肪生成底物,但谷氨酰胺不是。因此,我们研究了新鲜分离的人类皮脂腺的体外中间代谢,以确定其谷氨酰胺代谢相对于皮肤其他部分是否异常。
测定新鲜分离的人类胸部皮脂腺的糖酵解速率、葡萄糖和谷氨酰胺氧化以及通过磷酸戊糖途径的葡萄糖代谢。此外,使用分光光度法和高效液相色谱法分析皮脂腺中间代谢产物。此外,将腺体作为完整器官进行体外培养,以研究多胺合成前体和抑制剂对脂肪生成速率和模式以及DNA合成的影响。
我们证实人类皮脂腺是一个糖酵解和谷氨酰胺分解代谢的组织。葡萄糖主要转化为乳酸,只有6%的葡萄糖被氧化为二氧化碳。谷氨酰胺大部分转化为谷氨酸、丙氨酸、丝氨酸甘氨酸、天冬氨酸、苏氨酸、乳酸和氨,只有12%被氧化。我们还表明,人类皮脂腺的细胞增殖和脂肪生成需要外源性谷氨酰胺。然而,在没有谷氨酰胺的情况下,亚精胺可以完全恢复DNA合成和脂肪生成的速率。
尽管谷氨酰胺是皮脂腺脂肪生成的不良底物,但这不能归因于其分解代谢不足。我们已经表明谷氨酰胺是一种必需燃料,但它可以被外源性亚精胺替代。因此,我们建议在皮脂腺细胞中,谷氨酰胺和亚精胺都可能作为必需的嘌呤和嘧啶前体。