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Summary The activities of 3-phosphoglycerate dehydrogenase, an enzyme of serine biosynthesis, and serine hydroxymethyltransferase, serine dehydratase and serine aminotransferase, which are competing enzymes of serine utilization, were assayed in human colon carcinomas from patients and in transplantable rat sarcomas. Serine dehydratase and serine aminotransferase activities were absent, whereas 3-phosphoglycerate dehydrogenase and serine hydroxymethyltransferase activities were markedly increased in both tumour types. Serine hydroxymethyltransferase catalyses the formation of glycine and methylene tetrahydrofolate which are important precursors for nucleotide biosynthesis. The observed enzymic imbalance in these tumours ensures that an increased capacity for the synthesis of serine is coupled to its utilisation for nucleotide biosynthesis as a part of the biochemical commitment to cellular replication in cancer cells. That this pattern is found in sarcomas and carcinomas, and in tumours of human and rodent origin, signifies its universal importance for the biochemistry of the cancer cell and singles it out as a potential target site for anti-cancer chemotherapy.

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The activities of 3-phosphoglycerate dehydrogenase and serine hydroxymethyltransferase increased markedly during the transition of hepatoma cells from a resting non-proliferating culture into the proliferating growth phase. Activities declined as cells reached confluency and entered the plateau growth phase. This pattern was paralleled by changes in [14C]serine incorporation into nucleic acids. The experiments support the hypothesis that the biosynthesis of serine is metabolically coupled to its utilization for nucleotide precursor formation in cancer cells.

Fibromyalgia (FM) is characterized by generalized pain and chronic fatigue of unknown etiology. To evaluate the role of oxidative stress in this disorder, we measured plasma levels of ubiquinone-10, ubiquinol-10, free cholesterol (FC), cholesterol esters (CE), and free fatty acids (FFA) in patients with juvenile FM (n=10) and in healthy control subjects (n=67). Levels of FC and CE were significantly increased in juvenile FM as compared with controls, suggesting the presence of hypercholesterolemia in this disease. However, plasma level of ubiquinol-10 was significantly decreased and the ratio of ubiquinone-10 to total coenzyme Q10 (%CoQ10) was significantly increased in juvenile FM relative to healthy controls, suggesting that FM is associated with coenzyme Q10 deficiency and increased oxidative stress. Moreover, plasma level of FFA was significantly higher and the content of polyunsaturated fatty acids (PUFA) in total FFA was significantly lower in FM than in controls, suggesting increased tissue oxidative damage in juvenile FM. Interestingly, the content of monoenoic acids, such as oleic and palmitoleic acids, was significantly increased in FM relative to controls, probably to compensate for the loss of PUFA. Next, we examined the effect of ubiquinol-10 supplementation (100 mg/day for 12 weeks) in FM patients. This resulted in an increase in coenzyme Q10 levels and a decrease in %CoQ10. No changes were observed in FFA levels or their composition. However, plasma levels of FC and CE significantly decreased and the ratio of FC to CE also significantly decreased, suggesting that ubiquinol-10 supplementation improved cholesterol metabolism. Ubiquinol-10 supplementation also improved chronic fatigue scores as measured by the Chalder Fatigue Scale.