Human sebaceous glands engage in aerobic glycolysis and glutaminolysis.
BACKGROUND
The skin and its appendages support aerobic glycolytic and glutaminolytic metabolism. Their major fuels are glucose and glutamine, which are, however, largely catabolized anaerobically.


OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Downie
M M T
MM
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital, Box 232, Hills Road, Cambridge CB2 2QR, UK. mt_downie@yahoo.co.uk
Kealey
T
T
D000332:Aerobiosis / Q000502:physiology; D000596:Amino Acids / Q000378:metabolism; D000641:Ammonia / Q000378:metabolism; D002244:Carbon / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006019:Glycolysis / Q000502:physiology; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D009584:Nitrogen / Q000378:metabolism; D010084:Oxidation-Reduction; D010427:Pentose Phosphate Pathway / Q000502:physiology; D012627:Sebaceous Glands / Q000378:metabolism*; D013095:Spermidine / Q000032:analysis / Q000096:biosynthesis
D000596:Amino Acids; D005973:Glutamine; D019344:Lactic Acid; D002244:Carbon; D000641:Ammonia; D005947:Glucose; D009584:Nitrogen; D013095:Spermidine