Quantitative importance of non-skeletal-muscle sources of N tau-methylhistidine in urine.
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ABSTRACT:
SUBMITTER: Millward DJ
PROVIDER: S-EPMC1162081 | biostudies-other | 1980 Jul
REPOSITORIES: biostudies-other
Similar Datasets
Project description:The excretion of N tau-methylhistidine and creatinine was determined in a totally paralysed patient wih neither macroscopic nor microscopic detectable skeletal-muscle tissue. In this subject, it was possible for the first time to measure the basal non-skeletal-muscle-dependent excretion of N tau-methylhistidine and creatinine per 24 h and per kg of non-muscular body weight, 1.15 mumol (N tau-methylhistidine) and 35 mumol (creatinine) respectively. For the calculation of myofibrillar protein breakdown and skeletal-muscle mass on the basis of N tau-methylhistidine and creatinine excretion, the values have to be corrected for non-muscular sources. Our data show that skeletal-muscle tissue is the major contributor of N tau-methylhistidine in urine, since it contributes as much as 75% to the urinary excretion.
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Project description:The claim of Millward, Bates, Grimble, Brown, Nathan & Rennie [(1980) Biochem. J. 190. 225--228] that muscle actomyosin contributes as little as 25% of urinary N tau-methylhistidine is not consistent with other published data from that group [Bates, DeCoster, Grimble, Holloszy, Millward & Rennie (1980) J. Physiol. (London) 303, 41 P] or with literature values. It appears likely that the turnover rate of muscle actomyosin has been considerably underestimated and that when realistic rates of protein turnover are used, muscle tissue remains the major contributor of N tau-methylhistidine in urine.
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Project description:Mice and rats were injected with tracer doses of radioactive N tau-[Me-14C]methylhistidine in order to determine the recovery of the injected radioactivity and the extent of the metabolism of N tau-methylhistidine. In the first 27 h after injection, 96.3, 78.0 and 97.5% of radioactivity was excreted by female mice, male mice and male rats respectively. Recovery after 5 days of collection was 98.4 and 92.8% for female and male mice respectively. However, radioactivity associated with N tau-methylhistidine or its acetylated derivative accounted for 44, 86.5 and 96.0% of the excreted radioactivity for female mice, male mice and rats respectively. In female mice the remaining excreted radioactivity was associated with four major peaks of activity when the metabolites were separated by cation-exchange chromatography. In male mice there were only three of these metabolites present. After chromatographic purification, one metabolite was identified by mass spectroscopy to be 1-methylimidazole-4-acetic acid. Examination of the possible sources of this metabolite indicates that, in mice, N tau-methylhistidine is decarboxylated and enters the chain of reactions common to histamine metabolism. Such extensive metabolism precludes the use of N tau-methylhistidine excretion as an index of myofibrillar protein breakdown in mice.
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Project description:The tissue origin of 3-methylhistidine (N tau-methylhistidine) was investigated in adult female rats. The decay of labelling of urinary 3-methylhistidine was compared with the labelling of protein-bound 3-methylhistidine in skeletal muscle and intestine after the injection of [methyl-14C]methionine. The decay curve for urinary 3-methylhistidine was much steeper than that in muscle or intestine, falling to values lower than those in either tissue after 30 days. The lack of decay of labelling in muscle during the first 30 days is shown to result from the persistence of label in the precursor S-adenosylmethionine. The relative labelling of urinary, skeletal-muscle and intestinal 3-methylhistidine cannot be explained in terms of skeletal muscle accounting for a major proportion of urinary 3-methylhistidine. Measurements were also made of the steady-state synthesis rate of protein-bound 3-methylhistidine in intestinal smooth muscle in vivo in adult female rats. This involved measurement of the overall rate of protein synthesis and measurement of the relative rates of synthesis of 3-methylhistidine and of mixed protein. The synthesis rate of 3-methylhistidine was 29.1%/day, compared with the overall rate of 77.1%/day for mixed, non-mucosal intestinal protein. Measurement of the amount of 3-methylhistidine in skeletal muscle (0.632 +/- 0.024 mumol/g) and in the whole body (0.332 +/- 0.013 mumol/g) indicate that, although the muscle pool is 86% of the total, because of its slow turnover rate of 1.1-1.6%/day, it only accounts for 38-52% of the observed excretion. Measurements of the mass of the intestine (9.95 g/250 g body wt.) and protein-bound 3-methylhistidine content (0.160 mumol/g of tissue) indicate a pool size of 1.59 mumol/250 micrograms rat. Thus 463 nmol of the urinary excretion/day would originate from the intestine, 22% of the total. The tissue source of the remaining urinary excretion is not identified, but other non-muscle sources constituting about 10% of the whole-body pool could account for this with turnover rates of only 6%/day, a much lower value than the turnover rate in the intestine.
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