The Glycine Transporter GLYT1 in Human Intestine: Expression and Function

Abstract

Glycine is a well-documented cytoprotective agent and protects mammalian intestine against ischemiareperfusion injury, irradiation and experimentally induced colitis. The specific glycine transporter GLYT1 is found throughout the human intestine where it is responsible for some 30-50% of glycine uptake into intestinal epithelial cells across the basolateral membrane and appears to function to maintain glycine supply to enterocytes and colonocytes. This paper reviews current knowledge of GLYT1 and presents recent evidence supporting its essential role in glycine mediated cytoprotection in intestinal absorptive cells. Regulatory mechanisms involved in intestinal expression of GLYT1 are discussed and the potential of glycine for use as an anti-inflammatory, protective agent in the management of inflammatory bowel disease examined.

Serum Metabolomic Profiling of All-Cause Mortality: A Prospective Analysis in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study Cohort

“…Histidine may be independently inversely associated with age (51), and it can be metabolized to carnosine, a known antioxidant characterized as an "anti-aging" biochemical based on suppression of oxidative damage, glycation of proteins, and scavenging toxic age-related molecules (52). Glycine is the precursor of several molecular species, including purines and glutathione, and a substantial body of evidence supports its beneficial role in cytoprotection, antioxidation, antiinflammation responses, and metabolic regulation (53)(54)(55)(56)(57). Increased CVD mortality was also related to elevated serum mannose, consistent with findings from the Atherosclerosis Risk in Communities study (3), as well as to lysolipids (e.g., 1-linoleoyl-glycerophosphoethanolamine), which are considered important cell-signaling molecules that contribute to regulation of cell differentiation, growth, proliferation, and invasion (58)(59)(60)(61)(62), and to steroid hormones in the androgen pathway (e.g., 4-androsten-3β,17β-diol disulfate 1).…”

Stimulation of MC38 tumor growth by insulin analog X10 involves the serine synthesis pathway

“…These transporters have previously been reported to be expressed in normal intestinal epithelial cells, colon cancer, and various cancer cell lines (Yanagida et al 2001, Fuchs & Bode 2005, Broer 2008, Howard & Hirst 2011. Amino acids can be utilized in cancer cell for synthesis of protein and other macromolecules.…”

Reduction of Rapid Proliferating Tumour Cell Lines by Inhibition of the Specific Glycine Transporter GLYT1

“…Additionally, increased glycine concentration in tumour tissue of patients has been linked to poor patient prognosis [ 10 ]. Glycine can be transported into cells via a specific glycine transporter GLYT1 [ 26 , 30 ]. Previous studies in this group showed that under stress conditions extracellular glycine transported via GLYT1 supports GSH levels and cell survival [ 12 ].…”

“…Glycine can be transported into cells via the specific glycine transporters GLYT1 and GLYT2 (SLC6A9 and SLC6A5, respectively), and also by a variety of non-specific amino acid transporters: ATB 0,+ (SLC6A14), PAT1 (SLC36A1), PAT2 (SLC36A1), SNAT2 (SLC38A2) and SNAT4 (SLC38A4) [ 26 , 27 , 28 , 29 ]. While GLYT2 is mainly expressed in neuronal tissues, GLYT1 is expressed in many peripheral organs [ 30 , 31 ]. In comparison to the latter, non-specific transporters that accept multiple amino acids as substrates, GLYT1 is highly specific for glycine and N-methylglycine derivatives such as sarcosine, demonstrating a high affinity transport [ 26 ].…”