Glycine, phenylmethylester

Plasma glycine level is low in patients with obesity or diabetes and the improvement of insulin resistance increases plasma glycine concentration. In prospective studies, hypoglycinemia at baseline predicts the risk of developing type 2 diabetes and higher serum glycine level is associated with decreased risk of incident type 2 diabetes. Consistently, plasma glycine concentration is lower in the lean offspring of parents with type 2 diabetes compared to healthy subjects. Among patients with type 2 diabetes, hypoglycinemia occurs before clinical manifestations of the disease, but the pathophysiological mechanisms underlying glycine deficit and its potential clinical repercussions are unclear. Glycine participates in several metabolic pathways, being required for relevant human physiological processes. Humans synthesize glycine from glyoxylate, glucose (via serine), betaine and likely from threonine and during the endogenous synthesis of L-carnitine. Glycine conjugates bile acids and other acyl moieties producing acyl-glycine derivatives. The glycine cleavage system catalyzes glycine degradation to carbon dioxide and ammonium while tetrahydrofolate is converted into 5,10-methylene-tetrahydrofolate. Glycine is utilized to synthesize serine, sarcosine, purines, creatine, heme group, glutathione, and collagen. Glycine is a major quantitative component of collagen. In addition, the role of glycine maintaining collagen structure is critical, as glycine residues are required to stabilize the triple helix of the collagen molecule. This quality of glycine likely contributes to explain the occurrence of medial arterial calcification and the elevated cardiovascular risk associated with diabetes and chronic kidney disease, as emerging evidence links normal collagen content with the initiation and progression of vascular calcification in humans.

Glycine consists of a single carbon molecule attached to an amino and a carboxyl group. Its small size helps it to function as a flexible link in proteins and allows for the formation of helices, an extracellular signaling molecule, recognition sites on cell membranes and enzymes, a modifier of molecular activity via conjugation and glycine extension of hormone precursors, and an osmoprotectant. There is substantial experimental evidence that free glycine may have a role in protecting tissues against insults such as ischemia, hypoxia, and reperfusion. This impressive catalogue of functions makes an interesting contrast with glycine's perceived metabolic role as a nonessential amino acid. Glycine interconverts with serine to provide a mechanism for the transfer of activated one-carbon groups. Glycine has just been viewed as a convenient source of nitrogen to add to solutions of nutrients. Although this may have unexpected benefits when such solutions are used in clinical practice, it does raise the specter of a possible confounding effect in experiments when glycine is added to control solutions to make them isonitrogenous.

Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis (tricine-SDS-PAGE) is an efficient way of separating low molecular mass proteins. However, the standard system is quite complicated and specifically may not be useful when the separated proteins are to be recovered from the gel for quantitative analysis. Here, we describe a simplified system whereby these smaller proteins can be resolved in comparatively low percentage gels which have high compatibility with modern detectors such as UV and inductively coupled plasma-mass spectrometry (ICP-MS).