Effect of L-Histidine on Creatine, Histidine, and 1-Methylhistidine Excretion of Normal and Vit. E-Deficient Rabbits.

Abstract

I t has been shown(l,2) that Vit. E-deficient diet caused rabbits to excrete 1-methylhistidine in large amounts. Appeuance of this amino acid in urine generally precedes that of creatine making it one of the earliest detectable symptoms of nutritional muscular dystrophy. McManus( 1) has shown a diminished concentration af muscle carnosine and anserine suggesting an abnormality in the metabolism of these dipeptides. She believes that Vit. E-deficiency results in a hydrolysis of muscle anserine to beta-alanine and 1-methylhistidine as well as a decreased synthesis of anserine.Regardless of the causative mechanism, the loss of large amounts of 1-methylhistidine might itself produce secondary effects such as a significant drain on the body's reserve of the essential amino acid histidine. Our studies describe the effect of dietary L-histidine on excretion of creatine, histidine, and 1-methylhistidine of normal and Vit. E-deficient rabbits.Methods. Twelve male rabbits, divided into 4 equal groups, were fed the following diets ud Zib.: A. Dystrophy-producing diet of Young and Dinning(3) plus 8 rng alphatocopherol acetate thrice weekly: R. Dystrophy-producing diet containing 1 % L-histidine plus 8 mg oral alpha-tocopherol acetate thrice weekly: C. Dystrophy-producing diet: D. Dystrophy-producing diet containing 1 % L-histidine. When histidine was inmrporated into the diet, an equivalent weight of sucrose was deducted.Twenty-four hour urine samples were collected occasionally in a rabbit metabolism cage. Creatine and creatinine were determined by the method of Folin(4) while quantitative determinations of histidine and 1methylhistidine were made by Dowex-50 chromatography using the method of Tallan et a l . ( 5 ) .

Temporal metabolic response yields a dynamic biosignature of inflammation

“…histidinylhistidine and creatine abundance are linked. This is consistent with known metabolic pathways and validates the approach used to generate the models ( Smith and Ning, 1961 ).…”

“…Both IL1B and TNFα are potent stimulators of proteolysis, and GMCSF is a pro-inflammatory cytokine that stimulate proliferation and activation of phagocytic leukocytes capable of producing IL1B and TNFα ( Chang and Bistrian, 1998 ; Shiomi and Usui, 2015 ). These are the same three cytokines models that creatine appears in, and there has been some research showing an effect of histidine on creatine concentrations leading us to postulate that histidinylhistidine may be involved in creatine metabolism signaling ( Smith and Ning, 1961 ). If so, this effect would most likely be inhibitory.…”