The amino acid l-serine, one of the so-called non-essential amino acids, plays a central role in cellular proliferation. l-Serine is the predominant source of one-carbon groups for the de novo synthesis of purine nucleotides and deoxythymidine monophosphate. It has long been recognized that, in cell cultures, l-serine is a conditional essential amino acid, because it cannot be synthesized in sufficient quantities to meet the cellular demands for its utilization. In recent years, l-serine and the products of its metabolism have been recognized not only to be essential for cell proliferation, but also to be necessary for specific functions in the central nervous system. The findings of altered levels of serine and glycine in patients with psychiatric disorders and the severe neurological abnormalities in patients with defects of l-serine synthesis underscore the importance of l-serine in brain development and function. This paper reviews these recent insights into the role of l-serine and the pathways of l-serine utilization in disease and during development, in particular of the central nervous system.
Abbreviations used: CSF, cerebrospinal fluid; NMDA, N-methyl-d-aspartate; 3-PGDH, 3-phosphoglycerate dehydrogenase; PSP, phosphoserine phosphatase; SDH, serine dehydratase; SHMT, serine hydroxymethyltransferase; cSHMT, cytosolic SHMT; mSHMT, mitochondrial SHMT; SPT/AGT, serine:pyruvate/alanine:glyoxylate aminotransferase.