Quantitative excretion of 3-methylhistidine in urine of cats as a measure of in vivo skeletal muscle protein catabolism

Abstract

The purpose of this study was to evaluate the use of urinary 3-methylhistidine excretion as an index of in vivo skeletal muscle protein degradation in cats. The criterion for validation was the rapid and quantitative excretion of an intravenously administered dose of radiolabeled 3-methylhistidine (3-methyl- 14C). Four adult cats were maintained in individual metabolism cages and allowed free access to a purified diet (43.5% protein) and water for 4 weeks. The cats were then injected intravenously with 740 kBq 3-[ 14C]methylhistidine dihydrochloride diluted in 1 mL of saline. Twenty-four-hour urine samples were collected for 7 days. Total radioactivity in each urine sample was determined by direct counting. Quench correction was determined by using an external standard. The mean (±SEM) cumulative urinary recovery of 3-[ 14C]methylhistidine from the four cats was 94.9 ±3.5% at 48 hr following radioisotope injection. The mean (±SEM) cumulative urinary recovery of radioactivity from the four cats was 103.9 ± 2.2% at 7 days following radioisotope administration. There was no detectable radioactivity found in expired CO 2 and negligible amounts (mean ± SEM: 0.6 ± 0.5%) in the feces. Chromatography of urinary amino acids and radioactive urine metabolites revealed no significant radioactivity in any other peak besides 3-methylhistidine. Acid hydrolysis of urine resulted in no increase in 3-methylhistidine content or urine, indicating that there is no significant acetylation of 3-methylhistidine in this species. On the basis of these results, 3-methylhistidine does not appear to be metabolized and should therefore be a valid index of in vivo skeletal muscle protein degradation in the cat. Urinary 3-methylhistidine excretion should be useful for studying how nutritional, hormonal, and other physiological or pathological factors cause losses or gains in skeletal muscle protein in this species.