Unique aspects of lysine nutrition and metabolism

Lysine nutrition is unique among indispensable amino acids in that it can be conserved and can be fed 12 h out of phase (delayed supplement) with the other dietary amino acids. In piglets, high levels (2-6%) of L-lysine added to a 10% protein diet can be tolerated without obvious detrimental effects. In both rat and piglet liver preparations, the first enzyme in the saccharopine-dependent pathway of lysine catabolism, lysine a-ketoglutarate reductase (LKR), is found only in the mitochondrial matrix. For Lys catabolism to occur, Lys must first enter the matrix of the mitochondrion. LKR, saccharopine dehydrogenase, mitochondrial lysine uptake, and lysine oxidation (LOX) all increased >3-fold in rats fed high levels of dietary protein (up to 60%). The activities of mitochondrial Lys uptake and LOX were similar when expressed as mmol/(d center dot 100 g body weight). Thus, LOX can be a proxy for mitochondrial Lys uptake. Piglet liver LKR and LOX increase 5- to 10-fold when piglets are fed high-protein (50 or 75%) diets. In both the rat and piglet, after adapting to the high protein diet, the activity of LKR is 400-500 times that of LOX, suggesting that Lys uptake by a transporter(s) is rate limiting. Quantitative 24-h dietary infusion studies in piglets revealed that >80% of the Lys infused (4% of the diet) could not be recovered in the urine or body or accounted for by calculated Lys oxidation based on liver activity of LOX. Other pathways and tissues may account for the Lys oxidation in piglets.