Hippurate participates in the correction of metabolic acidosis

Hippurate (Hip), an endogenous conjugate, belongs to the group of uremic to xins. Hip stimulates P-independent glutaminase (PIG) localized at the proxi mal luminal membrane, desamidating glutamine with the formation of ammonia, a dominant and adaptive elimination product of H+. This appears to be impo rtant because metabolic acidosis (MAC) does not stimulate PIG. Moreover, Hi p inhibits ammonia production by P-dependent mitochondrial glutaminase (PDG ) that is primarily stimulated by MAC. By this mechanism, it shifts the amm onia production from mitochondria to proximal tubular lumen. MAC stimulates Hip synthesis in the liver and kidney and increases Hip plasma concentrati on and even fractional excretion by the kidney, which creates an effective regulatory loop of ammoniagenesis. Thus, it appears that Hip by its partici pation in the correction of MAC possesses the modulatory function.