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Pyroglutamic Acidosis OVERVIEW Pyroglutamic acidosis is a rare cause of high anion gap metabolic acidosis (HAGMA) pyroglutamic acid is also known as 5-oxoprolinemia produced from -glutamyl cysteine by the enzyme -glutamyl cyclotransferase catabolised by 5-oxoprolinase when glutathione levels are low, the activity of -glutamyl cyclotransferase is increased, resulting in pyroglutamic acid accumulation in glutathione-depleted states CAUSE Risk factors elderly paracetamol use (glutathione depletion by its metabolite NAPQI) sepsis (depletion of glutathione) flucloxacillin (inhibits 5-oxoprolinase) hepatic and renal impairment malnutrition pregnancy vigabatrin congenital enzyme deficiencies (glutathione synthase deficiency) Pyroglutamic acidosis results from disruption of the -glutamyl cycle 5-oxoproline (aka pyroglutamic acid) is produced from -glutamyl cysteine by the enzyme -glutamyl cyclotransferase -glutamyl cyclotransferase activity increases when glutathione levels are low, due to a loss of feedback inhibition from glutathione accumulation of pyroglutamic acid is thought to be due to depletion of the glutathione, particularly when glutathione synthetase is inhibited Decreased activity of 5-oxoprolinase, which breaks down pyroglutamic acid, may also play a role CLINICAL FEATURES manifestations of acidaemia e.g

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5.2 Regulation of T cell subtypes CD4/CD8 and Treg cells by GLP-1RA GLP-1R is expressed in various immune cell populations of NOD mice, with a higher proportion of mature CD4 + and CD8 + T cells (approximately 5%-6%)

doi: 10.1111/aos.13526