Pyruvate in the Correction of Intracellular Acidosis: A Metabolic Basis as a Novel Superior Buffer

Abstract

The review focuses on biochemical metabolisms of conventional buffers and emphasizes advantages of sodium pyruvate (Pyr) in the correction of intracellular acidosis. Exogenous lactate (Lac) as an alternative of natural buffer, bicarbonate, consumes intracellular protons on an equimolar basis, regenerating bicarbonate anions in plasma while the completion of gluconeogenesis and/or oxidation occurs via tricarboxylic-acid cycle in mitochondria mainly in liver and kidney, or heart. The general assumption that Lac is ‘metabolized to bicarbonate’ in liver to serve as a buffer has been questioned. Pyr as a novel buffer would be superior to conventional ones in the correction of metabolic acidosis. Several likely biochemical mechanisms of Pyr action are discussed. Experimental evidence, in vivo, strongly suggested that Pyr would be particularly efficient in the correction of severe acidemia: type A lactic acidosis, hypercapnia with cardiac arrest, and diabetic and alcoholic ketoacidosis in animal experiments and clinic settings. Because of its multi-cytoprotection, Pyrs not only correct acidosis, but also benefit theunderlying dysfunction of vital organs. In addition, Pyr is also a potential buffer component of dialysis solutions. However, the instability of Pyr in aqueous solutions restricts its clinical applications as a therapeutic agent. Attempts to create a stable Pyr preparation are needed.

Buffer-dependent regulation of aquaporin-1 expression and function in human peritoneal mesothelial cells

“…To act as an alkalizer, intracellular lactate must be converted to pyruvate, which in turn can be oxidized in mitochondria to CO 2 and water (H 2 O) or enter gluconeogenesis and titrate protons. L-PDF buffered at an acidic or physiological pH, but not B-PDF, reduces mitochondrial activity in human monocytes [39] and HPMC [40] and suppresses aerobic cell metabolism and adenosine triphosphate generation [41], all of which may result in intracellular acidosis [42] and reduce AQP-1 abundance. In the presence of high bicarbonate concentrations, however, an inhibitory effect of lactate was absent.…”

Neuroprotective Effects of Ethyl Pyruvate on Brain Energy Metabolism after Ischemia-Reperfusion Injury: A 31P-Nuclear Magnetic Resonance Study

“…Therefore, exogenous pyruvate not only raises pH i restoring pH-sensitive phosphofructokinase (PFK-1) activity, but also restores glycolysis in anaerobic conditions by increasing NAD ? /NADH ratio, which is critical for glycolysis at the level of glyceraldehyde-3-phosphate dehydrogenase [48]. It is speculated that neuroprotective effects of EP might be attributed to the less acidic intracellular condition and increased NAD ?…”

Protection by Pyruvate Infusion in a Rat Model of Severe Intestinal Ischemia-Reperfusion Injury

“…3). Infusion of a metabolizable anion such as pyruvate together with the cation sodium may result in systemic alkalinization [21], and both mitochondrial-dependent oxidative metabolism of pyruvate and its reduction to lactate consume hydrogen ions and, thus, may decrease intracellular acidosis [18,19,22].…”