The figure above represents one-carbon and glutathione metabolism in liver cells. Rectangular boxes represent substrates, the arrows are biochemical reactions, and the blue ovals contain the acronyms for the enzymes. One-carbon metabolism is composed of the cytosolic and mitochondrial folate cycles (the folate substrates are in pink rectangles) and the methionine cycle. Glutathione (GSH) is synthesized via the transsulfuration pathway (purple rectangles). The cytoslic folate cycle is involved in purine and pyrimidine synthesis.
The methionine cycle mediates a host of methyl-transfer reactions, including those of DNA methylation (DNMT). Homocysteine (Hcy) is a major biomarker for cardiovascular disease, and GSH is one of the main anti-oxidants produced by the liver. Folate is one of the B vitamins (B-9). Vitamin B-12 is a co-factor for the MS reaction, and vitamin B-6 is a cofactor for the CBS, CTGL, GDC, and both SHMT reactions. Thus it is not surpising that deficencies in dietary B-vitamin input and genetic polymorphisms for the enzymes in one-carbon metabolism are associated with a host of human health concerns, including cancer, cardiovascular disease and neural tube defects.
A mathematical model corresponding to this diagram was used in Reed at al. to investigate GSH synthesis and the metabolic profiles of Down Syndrome and auti