Glyoxylate Reductase Activity of Lactate Dehydrogenase

“…Although not shown for human platelets, pyruvate is efficiently transported into cardiac myocytes [41] and hepatocytes [42]. This suggests that pyruvate enters the platelets and prevents the consumption of GLOX in the LDH reaction, as has been reported for other cells by several groups [14][15][16][17]. GLOX has also been shown to inhibit pyruvate dehydrogenase without being consumed in heart muscle [43,44], thus reducing the supply of acetylCoA to the citric acid cycle, thus explaining reports on inhibition by GLOX of respiration in many cells [6,10,19] and the lowering of the ATP level.…”

Section: Metabolic Inhibitorsmentioning

confidence: 72%

“…GLOX is also an amine acceptor from alanine and other amino acids by amino transferases [13]. However, there are many reports of GLOX substituting pyruvate in the lactate dehydrogenase in several cell types [14][15][16][17][18][19], which clearly would affect energy metabolism. Platelets have also been reported to contain glyoxylase [20].…”

Section: Introductionmentioning

confidence: 99%

Glyoxylate lowers metabolic ATP in human platelets without altering adenylate energy charge or aggregation

Dangelmaier

Holmsen

2013

Platelets

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Human blood platelets adhere to exposed collagen at the site of vascular injury, initiating a signaling cascade leading to fibrinogen activation, secretion of granules and aggregation, thus producing a stable thrombus. All these steps require metabolic ATP. In this study we have labeled the metabolic pool of ATP with nucleotides, treated platelets with various inhibitors and have monitored their ability to be activated. Incubating platelets with glyoxylate dramatically reduced the ATP level without a change in the adenylate energy charge (AEC). This reduction of ATP did not affect ADP-induced primary or secondary aggregation, whereas glyoxal, methyl glyoxal, or the combination of antimycin plus deoxyglucose reduced both ATP and AEC and inhibited aggregation. The reduction of ATP by glyoxylate was almost quantitatively matched by an increase in hypoxanthine without elevation of ADP. AMP, IMP or inosine, acetoacetate, aspartate, or glutamate had no effect on glyoxylate-induced breakdown of ATP, while pyruvate stopped the ATP reduction fast and efficiently. Glyoxylate also lowered the citrate content. The glyoxylate-induced breakdown of ATP coincided with an increase in fructose-1,6-bisphosphate, indicating that the phosphofructokinase reaction was the main ATP-consuming step. Glyoxylate was a substrate for lactate dehydrogenase although with a Km almost 100 times higher than pyruvate. We suggest that glyoxylate primarily competes with pyruvate in the pyruvate dehydrogenase reaction, thus lowering the citrate concentration, which in turn activates phosphofructokinase. Clearly, lowering of ATP in the cytosol by more than 50% does not affect platelet aggregation provided that the AEC is not reduced.

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“…The finding that both types (M and H) of LDH have an identical action has already been described (1,2,6). This reaction in reversed direction is either markedly weaker or hardly notable (3).…”

mentioning

confidence: 67%