Topic
Serine hydroxymethyltransferase
About: Serine hydroxymethyltransferase is a research topic. Over the lifetime, 713 publications have been published within this topic receiving 19556 citations. The topic is also known as: Ser_HO-MeTrfase & IPR001085.
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TL;DR: Glycine plays an important role in metabolic regulation, anti-oxidative reactions, and neurological function and has been used to prevent tissue injury, promote protein synthesis and wound healing, and improve immunity.
Abstract: Glycine is a major amino acid in mammals and other animals It is synthesized from serine, threonine, choline, and hydroxyproline via inter-organ metabolism involving primarily the liver and kidneys Under normal feeding conditions, glycine is not adequately synthesized in birds or in other animals, particularly in a diseased state Glycine degradation occurs through three pathways: the glycine cleavage system (GCS), serine hydroxymethyltransferase, and conversion to glyoxylate by peroxisomal d-amino acid oxidase Among these pathways, GCS is the major enzyme to initiate glycine degradation to form ammonia and CO2 in animals In addition, glycine is utilized for the biosynthesis of glutathione, heme, creatine, nucleic acids, and uric acid Furthermore, glycine is a significant component of bile acids secreted into the lumen of the small intestine that is necessary for the digestion of dietary fat and the absorption of long-chain fatty acids Glycine plays an important role in metabolic regulation, anti-oxidative reactions, and neurological function Thus, this nutrient has been used to: (1) prevent tissue injury; (2) enhance anti-oxidative capacity; (3) promote protein synthesis and wound healing; (4) improve immunity; and (5) treat metabolic disorders in obesity, diabetes, cardiovascular disease, ischemia-reperfusion injuries, cancers, and various inflammatory diseases These multiple beneficial effects of glycine, coupled with its insufficient de novo synthesis, support the notion that it is a conditionally essential and also a functional amino acid for mammals (including pigs and humans)
512 citations
TL;DR: Plant mitochondria possess all the necessary enzymatic equipment for de novo synthesis of tetrahydrofolate and lipoic acid, serving as cofactors for glycine decarboxylase and serine hydroxymethyltransferase functioning.
395 citations
TL;DR: It is demonstrated that the serine catabolic enzyme SHMT2 is induced upon hypoxic stress and is critical for maintaining NADPH production and redox balance to support tumor cell survival and growth.
Abstract: The de novo synthesis of the non-essential amino acid serine is often upregulated in cancer. In this study we demonstrate that the serine catabolic enzyme, mitochondrial serine hydroxymethyltransferase (SHMT2) is induced when Myc-transformed cells are subjected to hypoxia. In mitochondria, SHMT2 can initiate the degradation of serine to CO2 and NH4+ resulting in net production of NADPH from NADP+. Knockdown of SHMT2 in Myc-dependent cells reduced cellular NADPH/NADP+ ratio, increased cellular reactive oxygen species (ROS) and triggered hypoxia-induced cell death. In vivo, SHMT2 suppression led to impaired tumor growth. In myc-amplified neuroblastoma patient samples, there was a significant correlation between SHMT2 and Hypoxia-inducible factor-1 α (HIF-1α) and SHMT2 expression correlated with unfavorable patient prognosis. Together these data demonstrate that mitochondrial serine catabolism supports tumor growth by maintaining mitochondrial redox balance and cell survival.
330 citations
TL;DR: A key role is identified for serine and glycine metabolism in the survival of brain cancer cells within the ischaemic zones of gliomas and SHMT2 activity limits that of pyruvate kinase and reduces oxygen consumption, eliciting a metabolic state that confers a profound survival advantage to cells in poorly vascularized tumour regions.
Abstract: Cancer cells adapt their metabolic processes to support rapid proliferation, but less is known about how cancer cells alter metabolism to promote cell survival in a poorly vascularized tumour microenvironment. Here we identify a key role for serine and glycine metabolism in the survival of brain cancer cells within the ischaemic zones of gliomas. In human glioblastoma multiforme, mitochondrial serine hydroxymethyltransferase (SHMT2) and glycine decarboxylase (GLDC) are highly expressed in the pseudopalisading cells that surround necrotic foci. We find that SHMT2 activity limits that of pyruvate kinase (PKM2) and reduces oxygen consumption, eliciting a metabolic state that confers a profound survival advantage to cells in poorly vascularized tumour regions. GLDC inhibition impairs cells with high SHMT2 levels as the excess glycine not metabolized by GLDC can be converted to the toxic molecules aminoacetone and methylglyoxal. Thus, SHMT2 is required for cancer cells to adapt to the tumour environment, but also renders these cells sensitive to glycine cleavage system inhibition.
285 citations
TL;DR: The hypothesis was proposed that the mitochondrial isoenzyme of serine hydroxymethyltransferase is associated together with serine aminotransferase in a pathway for gluconeogenesis from protein-derived amino acids such as glycine and hydroxyproline.
257 citations