92.8.1 Disorders of Serine Synthesis

It has been published that M1 and M2 cells have the same proliferation rate under regular in vitro culture conditions, but in vivo M2 cells form much larger xenograft tumors than M1 cells (). Similar to previous findings, we did not observe a significant difference in cell proliferation between M1 and M2 cells in complete medium (). Based on the accumulation of glycolytic intermediates that could contribute to de novo synthesis, we next tested whether M2 cells exhibit a proliferative advantage upon serine starvation. Indeed, M1 cells exhibited greater reduction in proliferation upon serine withdrawal than M2 cells, suggesting that M2 cells are less dependent on exogenous serine ().

Pyruvate kinase M2 promotes de novo serine synthesis …

The major source of carbon units for nucleic acid synthesis comes from serine.


The method of NMR spectroscopy was used to investigate the role of voltage-dependent anion channels in the outer mitochondrial membrane in the mechanism of ethanol hepatotoxicity using the synthesis of serine and exchange of methyl groups in hepatocytes metabolizing 13C-labeled glycine. Here we present and describe a methodological approach developed for the independent monitoring of the synthesis of serine in two intracellular compartments: the cytoplasm and mitochondria of intact hepatocytes, and quantification of different serine isotopomers synthesized in hepatocytes from 13C-labeled glycine. The data obtained indicate that the treatment of cells with ethanol as well as cysteamine (specific inhibitor of mitochondrial synthesis of serine) suppressed the level of mitochondria but not cytoplasmic serine isotopomers. It is concluded that the decrease in the production of mitochondrial serine isotopomers in hepatocytes exposed to ethanol can be caused not only by decreased permeability of the outer mitochondrial membrane due to the closure of voltage-dependent anion channels and suppression of the exchange of substrates of serine synthesis in mitochondria but also by the restoration of the cytoplasmic and/or mitochondrial pool of pyridine nucleotides (NADH) during the oxidation of ethanol. Our work reveals a new mechanism of action of ethanol (alcohol intoxication) in hepatocytes through the regulation of glycine metabolism and opens new possibilities in the treatment of alcohol poisoning.

THE SYNTHESIS OF SERINE - Journal of Biological …

Based on the present finding there may be two distinct ways to exploit the selective expression of PKM2 by tumor cells to enhance cancer therapies. One way is using PKM2 activators to increase its enzyme activity to restore glycolytic flux from PEP to pyruvate so that less 3-PG accumulates. Currently there are PKM2 activators under development (, ). The present studies also suggest that an alternative strategy might be to develop drugs that inhibit one of the enzymes in the serine synthetic pathway.

Figure 7 - Synthesis of Serine and Glycine. Note that this pathway actually yields energy and carbon for other uses. R (tetrahydropholate)

Serine and Functional Metabolites in Cancer - …

The biosynthesis of serine and glycine constitute a major metabolic pathway that plays a central role in the formation of other amino acids, nucleic acids and phospholipids. When is grown on glucose, fully 15% of carbon assimilated passes through the serine pathway. Synthesis of serine and glycine starts with oxidation of 3-phosphoglycerate forming 3-phosphohydroxy pyruvate and NADH. A transamination reaction with glutamate forms 3-phosphoserine and removal of the phosphate yields serine. Glycine is generated by removal of the methyl group from serine. Energy is not required for this pathway, in fact it yields energy in the form of reduced NADH.

Serine and Functional Metabolites in Cancer

Methionine is synthesized from oxaloacetate. Succinyl-CoA participates and cysteine donates a sulfur group to the molecule. Oxaloacetate is first converted into homoserine as described above in the threonine biosynthetic pathway. Homoserine then has a sulfur attached to the end in two steps and finally methionine is formed by the addition of a methyl group.

T1 - [Effect of ethanol on synthesis of serine and exchange of methyl groups in hepatocytes by NMR spectroscopy].

CA1217158A - Enzymatic synthesis of l-serine - Google …

Trytophan synthesis is complex and involves 5 steps from chorismate. Glutamate donates an amine group in the first step of the pathway and pyruvate is lost from chorismate. In the next threes steps a ribose sugar is added, this eventually contributes to the 5 membered ring of tryptophan. Energy is contributed to the process in the form of hydrolysis of pyrophosphate. This hydrolysis helps drive the addition of the ribose sugar in the second step of the reaction. In the last step of the pathway serine serves as the donor of the carbon amino group of tryptophan.

acid synthesis comes from serine

Synthesis of the aromatic amino acids begins with the synthesis of chorismate - an important intermediate for many biosynthetic pathways. Phosphoenol pyruvate and erythrose 4-phosphate serve as beginning substrates for the pathway. A price of one NADPH + H+ and one ATP is exacted for every chorismate formed. In the sixth step of the synthesis another phosphoenol pyruvate molecule is added to the growing molecule.

disorder stemming from the patient's deficiency in thrombin synthesis

Synthesis of cysteine is a two step reaction. Serine and acetyl-CoA combine to form -acetylserine. Sulfide from is then added to -acetylserine to form cysteine. The pathway for cysteine synthesis was covered in .