Age-Dependent Changes in the Rate of Myofibrillar Protein Degradation in Humans as Assessed by 3-Methylhistidine and Creatinine Excretion

Abstract

1. Urinary excretion of 3-methylhistidine and creatinine have been measured in normal male and female humans ranging in age from pre-term neonates to 68 years to assess changes in the rate of muscle protein degradation and in muscle mass. 2. The 3-methylhistidine excretion by six adult men was measured before and after subjects were transferred to meat-free diets. It was established that a meat-free diet should be eaten for a minimum of 3 days before urine collection to eliminate exogenous sources of 3-methylhistidine. 3. The 3-methylhistidine/creatinine excretion ratio declined about twofold between normal full-term birth and maturity. The ratio in pre-term neonates was higher than for full-term neonates. 4. The variability of 3-methylhistidine/creatinine ratios between individual untime urine samples within a subject is similar to the variability between different subjects with total daily collections. 5. The 3-methylhistidine content of human muscle averaged 3.63 +/- 0.06 micromol/g for subjects aged between 4 and 65 years with protein accounting for 20.4 +/- 0.8% of muscle weight. These values are used to relate 3-methylhistidine excretion to muscle protein degradation. 6. It is concluded that control groups must be matched by age and sex to the group being examined. Where creatinine excretion is not perturbed it can be used as a reference base for comparisons of 3-methylhistidine excretion to indicate the average fractional degradation rates of muscle protein.

Protein Turnover With Special Reference to Man

“…On the other hand, to the extent that some 3-MH may be derived from sources other than skeletal muscle (section 2.2) the method will over-estimate the contribution of muscle. Since, by comparison with other species, the estimate of Tomas et al (1979) seems reasonable, perhaps the two errors cancel out. However, a recent study in which muscle protein synthesis was measured in biopsies during infusion of [1-13C]leucine produced a much higher estimate.…”

“…For the special case of muscle, the method introduced by Haverberg and co-workers has been widely used, in which the 24 h excretion of 3-methylhistidine (3-MH) is taken as a measure of the rate of breakdown of myofibrillar proteins in skeletal muscle (Haverberg, Omstedt, Munro & Young, 1975;Young & Munro, 1978;Tomas, Ballard & Pope, 1979). It has recently been suggested that significant amounts of 3-MH are derived from tissues other than skeletal muscle.…”

“…However, there are some disturbing discrepancies for man. On the basis of 3-MH excretion (see section 2.2) Tomas et al (1979) estimated that in a 70 kg man, muscle protein turnover would be about 80 g. d-1, or about 25% of whole body turnover. They suggested that this might be an underestimate, because the method measures the turnover rate of the myofibrillar proteins and does not take account of the faster turnover of the sarcoplasmic proteins.…”

Über den Einfluß der Nahrungszusammensetzung auf die Ausscheidung von 3-Methylhistidin und Kreatinin im Harn

“…Deshalb wird die Ausscheidung von 3-Methylhistidin als Maß für den Abbau von Muskelprotein angesehen und für MUskelproteinumsatzbestimmungen verwendet, wobei man für die Berechnung der Muskelmasse üblicherweise die Kreätinin-Ausscheidung heranzieht (6). Wesentlich für die Aussagekraft bei diesem Verfahren ist die Erfassung des 3-Methylhistidin mit endogenem Ursprung, was das Einhalten einer 3-Methylhistidm-freien, d.h. fleischfreien Diät erforderlieh macht (7,8), und woran viele Untersuchungen auf diesem Sektor scheitern, intravenös verabreichtes 3-Methylhistidin wird quantitativ im Urin ausgeschieden (3) und bei einer 3-Methylhistidin-freien Diät sinkt die 3-MethylhistidinAusscheiderate innerhalb von 3-5 Tagen auf einen konstanten Wert herab, ohne mit signifikanten Veränderungen in der Kreatinin-Ausscheidung einherzugehen (7,8).…”

The 3-methylhistidine content of human tissues

“…In measurements of 3-MeH excretion after injury (Williamson et al 1977), we calculated the myofibrillar protein breakdown rate assuming the 3-MeH content of muscle to be 1.6prnol/g fat-free dry weight (Asatoor & Armstrong, 1967). Subsequent work (Bilmazes et al 1978;Holbrook et al 1979;Tomas et al 1979), has shown this value to be an underestimate, and in consequence calculation of muscle protein breakdown falsely high. We have therefore measured the 3-MeH content of several tissues obtained from adults post-i?2ortem in order to compare it with the published values from human muscle, to examine variations between individuals and from one muscle to another, and t o investigate the 3-MeH content of non-muscular tissues.…”