The methionine cycle and folate cycle explored in mature erythrocytes

Abstract

The glycolytic pathway, the Rapoport-Luebering Shunt, and the Pentose Phosphate Pathway (PPP) are important metabolic pathways in erythrocytes. The glycolytic pathway is the main provider for energy metabolites and the PPP for the antioxidant metabolite, nicotinamide adenine dinucleotide phosphate (NADPH). Through these pathways the erythrocyte is provided with most of the energy and antioxidant metabolites needed for a 120-day survival. However, the erythrocytes metabolism goes beyond glycolysis and the PPP. Metabolomic studies showed that the one-carbon metabolism plays a role in erythrocytes. Here, a literature review is given about the one-carbon metabolism in mature erythrocytes to show the current understanding, to give insights into knowledge gaps, and to discuss future research implications. This overview shows that the transmethylation, transsulfuration, and the folate cycle play important roles in the mature erythrocyte. The main purposes of these three metabolic pathways are to methylate metabolites, and to generate antioxidants for balancing the redox level. Blood disorders often have a defect which involves or affects a part of the one-carbon metabolism, including haemoglobinopathies, enzyme deficiencies, and dietary metabolite deficiencies. These disorders point out the relevance of a solid antioxidant system through the methionine cycle and the folate cycle to maintain the redox balance and promote erythrocyte survival. In addition, regulation of the one-carbon metabolism in blood storage is of crucial importance for an optimal blood transfusion. Altogether, the provided overview of one-carbon metabolism in mature erythrocytes aims to aid in the further understanding of the erythrocytes one-carbon metabolism and its role in blood disorders, and blood storage and transfusion.