Glyoxylate from glycine

This pyridoxal 5-phosphate-dependent enzyme [EC 2.6.1.4] catalyzes the transamination of glyoxylate from L-glutamate to produce glycine and a-ketoglutarate. 

Oxalate is an end product of metabolism, predominantly derived from breakdown of glyoxylate and glycine. Plasma concentration of oxalate is 1,0 to 2.4mg/L (11 to 27fxmol/L) and it is excreted in the urine at a rate of 17.5 to 35.1 mg/24 hours (200 to 400pmol/24 hours). Only 10% to 15% of urinary oxalate is derived directly from dietary sources. Intestinal oxalate absorption is increased when the availability of calcium in the intestine is reduced. Hyperoxaluria is... 

Besides ascorbic acid, glycine is the most important source of oxalic acid (W5). The metabolic pathway leading from glycine to oxalic acid via glyoxylic acid (which can be readily converted to glycolic acid) and the enzyme systems involved in that pathway have been recently... 

Fig. 4. Scheme showing the pathway leading from glycine to oxalic acid and the other metabolic transformations of glyoxylic acid. 

Oxalate, produced from glycine or obtained from the diet, forms precipitates with calcium. Kidney stones (renal calculi) are often composed of calcium oxalate. A lack of the transaminase that can convert glyoxylate to glycine (see Fig 39.6) leads to the disease primary oxaluria type I (PH 1). This disease has a consequence of renal failure attributable to excessive accumulation of oxalate in the kidney. 

Althongh glyoxalate can be transaminated back to glycine, this is not really considered a biosynthetic ronte for new glycine, becanse the primary ronte for glyoxylate formation is from glycine oxidation. 

In many green tissues in the light serine is made from glycolic acid by way of glyoxylate and glycine by conversion of two molecules of glycine to one each of serine, CO2 and ammonia. This is an essentially irreversible process in the mitochondria. Relatively little is known of the separate existence and operation of serine hydroxymethyl transferase which would be necessary for... 

A carboxylic acid, normally excreted in the urine in small amounts. It is a constituent of many urinary tract stones. High levels of oxalic acid are excreted in the urine in the rare inborn error of metabolism, primary hyperoxaluria. In this disorder renal stones composed of oxalate are formed and death results from progressive renal failure. The increase in the urinary excretion of oxalic acid appears to be derived from glycine as a result of deficient glyoxylic acid-glycine transamination. 

Glyoxylate could be formed from glycine mther by the action of glycine oxidase SS) or by transamination SS, 34). Glycine oxidase is a flavoprotein that has been found in liver and kidney. Because of its comparatively high Km value (0.04 M) and its low turnover number it generally is considered not to have any considerable role in the metabolism of gl3rcine. 

Glycinuria results from a defect in renal tubular reabsorption. The defect in primary hyperoxaluria is the failure to catabolize glyoxylate formed by deamination of glycine. Subsequent oxidation of glyoxylate to oxalate results in urohthiasis, nephrocalcinosis, and early mortality from renal failure or hypertension. 

Addition of nucleophiles to electrophilic glycine templates has served as an excellent means of synthesis of a-amino acid derivatives [2c, 4—6]. In particular, imines derived from a-ethyl glyoxylate are excellent electrophiles for stereoselective construction of optically active molecules [32], This research and retrosyn-thetic analysis led us to believe that amine-catalyzed asymmetric Mannich-type additions of unmodified ketones to glyoxylate derived imines would be an attractive route for synthesis of y-keto-ce-amino acid derivatives [33], Initially, L-proline-catalyzed direct asymmetric Mannich reaction with acetone and N-PMP-protected a-ethyl glyoxylate was examined in different solvents. The Mannich-type reaction was effective in all solvents tested and the corresponding amino acid derivative was isolated in excellent yield and enantioselectivity (ee >95 %). Direct asymmetric Mannich-type additions with other ketones afford Mannich adducts in good yield and excellent regio-, diastereo- and enantioselectivity (Eq. 8). 

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