β-Alanine and orotate as supplements for cardiac protection

-Alanine is a rate-limiting precursor for synthesis of the dipeptide carnosine (-alanyl-L-histidine), which is produced within and stored in high concentrations in skeletal muscle, heart and olfactory receptor neurons. 1 2 -Alanine supplementation has been shown to boost the carnosine content of skeletal muscle. This reflects the fact that the Km of carnosine synthase for -alanine (in excess of 1 mM) is far higher than the -alanine content of tissues; its Km for histidine is two orders of magnitude lower, such that intracellular histidine levels are not ratelimiting for carnosine synthesis. 3 -alanine is produced in the liver during catabolism of uracil; after its release to plasma, it can be transported into tissues that require it for carnosine synthesis. Plasma levels of -alanine also increase when carnosine is ingested in flesh foods; particularly in humans, carnosinase activity in plasma rapidly cleaves carnosine to its precursors -alanine and histidine. The pK a of the imidazole ring of carnosine is 6.83, which makes it an ideal physiological buffer for tissues when glycolytic production of lactic acid is high. 3 (The pK a of free histidine's imidazole ring is around 6, so converting histidine to carnosine makes it a more effective buffer.) Most studies with supplemental -alanine have focused on skeletal muscle and athletic performance; many studies have concluded that -alanine supplementation can both boost muscle carnosine content and aid performance in high-intensity anaerobic workouts in which lactic acid is generated, presumably by preventing counterproductive reductions in intracellular pH.