Skeletal muscle protein is very important for protein and amino acid metabolism in the homeostasis of the whole body, because skeletal muscle accounts for the largest amount of tissue. Therefore, it is necessary to measure the rate of muscle protein synthesis and degradation. Urinary Nτ-methylhistidine (MeHis) is used as an index of myofibrillar protein degradation. It was demonstrated in this study using rats that 75% of MeHis in urine originated from skeletal muscle and that 25% originated from skin and intestine. Furthermore, it was suggested that there was a rapid turnover of myofibrils, because the specific radioactivity of MeHis in urine and muscle protein differed after administration of radioactive methionine. Several factors influencing muscle protein degradation were studied using MeHis release from perfused hindquarter muscles and isolated muscles. Insulin, known to be an anabolic hormone, it inhibited the degradation of muscle protein, particularly myofibrillar protein, in diabetic rats. Cysteine proteinases might be involved in muscle protein degradation, because leupeptin inhibited the release of MeHis and tyrosine from isolated muscle. Muscle protein degradation was also affected by the modification of muscle protein by active oxygen species or free radicals by feeding rats a vitamin E-deficient diet or iron overload. In these studies, a new method for determination of MeHis was developed, capable of measuring low concentrations of MeHis in plasma and medium. This method would allow acute changes in muscle protein degradation to be evaluated.
It is well known that dietary xenobiotics and protein nutrition affect cholesterol and serum lipoprotein metabolism, although these precise mechanism has not been fully clarified. Treatment of rats with xenobiotics such as polychlorinated biphenyls (PCB) resulted in hyper-α-lipoproteinemia, characterized by an increase of apolipoprotein A-I (apo A-I) and replacement of apo E by apo A-I. Dietary PCB increased the hepatic levels of mRNA for apo A-I and HMG-CoA reductase. In hepatocyte culture, a direct effect of PCB on hepatocytes was revealed. The dietary level of protein regulated the expression of the liver apo A-I gene transcriptionally in a liver-specific manner. Soy protein isolate (SPI) decreased the cholesterol level of very-low-density lipoproteins and of high-density lipoproteins in comparison with casein. SPI lowered the level of apo E-rich lipoproteins, and then decreased that of apo A-I-rich lipoproteins. The hepatic apo A-I mRNA level was decreased by SPI, and elevated by addition of methionine. These results demonstrate that dietary xenobiotics and protein are regulators of apo A-I gene expression and the serum level of high-density lipoproteins.