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Biomedical subjects

H N Munro

Publications and source records attributed to H N Munro.

At least 19 recordsLinked to original sources
PubMed1979

Effect of glucocorticoid administration on the rate of muscle protein breakdown in vivo in rats, as measured by urinary excretion of N tau-methylhistidine.

The role of glucocorticoids in regulating the rate of muscle protein breakdown was evaluated by measuring excretion of N(tau)-methylhistidine during administration of various doses of corticosterone to adrenalectomized rats. Groups of rats received daily subcutaneous injections of 0, 0.2, 0.5, 1.0, 5.0 or 10.0mg of corticosterone/day per 100g body wt. for 7 days, followed by 3 days without hormone treatment, after which they were killed. A group with intact adrenal glands served as an additional control. All animals were pair-fed with the untreated adrenalectomized group. No significant differences were noted in growth rate or N(tau)-methylhistidine excretion between the intact or adrenalectomized control groups, or those given 0.2, 0.5 and 1.0mg of corticosterone, whereas growth ceased and N(tau)-methylhistidine excretion rose markedly in the groups receiving 5 and 10mg of corticosterone. After these two high doses of corticosterone, but not after lower doses, there was a loss of weight of the gastrocnemius muscle per 100g of final body wt., but not of the soleus and extensor digitorum longus muscles. The two highest doses of corticosterone also resulted in an increase in liver weight per 100g of final body wt. Lower doses of corticosterone did not cause these changes. Plasma corticosterone concentrations, measured on the final day of injection and again at the time of killing, were decreased to near zero by adrenalectomy and were little raised by doses of 0.2 and 0.5mg daily, but were increased to within the normal range by the 1mg dose. At 5 and 10mg doses, plasma corticosterone concentrations were sustained at 2-3 times those of intact rats, and thus in the range reported for rats exposed to severe stress. Rats given 5 and 10mg doses of corticosterone had glycosuria, and showed considerably elevated concentrations of insulin in the plasma. It is concluded that plasma concentrations of glucocorticoids within the normal range do not regulate the rate of muscle protein breakdown, whereas excessive plasma concentrations of corticosteroids, equivalent to those observed in severe stress, can accelerate muscle protein breakdown.

Adrenalectomy↗
PubMed1979

Release of in vitro-synthesized poly(A)-containing RNA from isolated rat liver nuclei: characterization of the ribonucleoprotein particles involved.

Nuclei isolated from rat liver were incubated under conditions in which RNA continued to be labeled with precursors for long periods. After 1 hr, during which the rate of RNA synthesis was constant, 25-30% of the newly synthesized RNA was recovered in the postnuclear supernatant. About 3-5% of this fraction was characterized as poly(A)-containing ribonucleoproteins by the following criteria: (i) characteristic elution profile in oligo(dT)-cellulose chromatography; (ii) size distribution of the molecules and their deproteinized RNAs; (iii) buoyant densities in CsCl gradients; (iv) presence of RNaseresistant fragments resembling poly(A)-protein complexes; and (v) identification of the protein components by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. The sensitivity of labeling of the RNA synthesized and released from the nuclei to low doses of alpha-amanitin suggests the presence of polymerase II products in the particles. Comparison of the sizes of proteins in these particles with those of free and polysomal messenger ribonucleoproteins as well as with heterogenous nuclear ribonucleoproteins indicates that the released particles contain a protein of 78,000 daltons, which is also present in the other three classes of ribonucleoproteins, presumably at the 3'-poly(A) segments. In addition, a few other proteins, similar in size to those found in the cytoplasmic ribonucleoproteins, were also present in the released particles. It is suggested that proteins associated with heterogenous nuclear RNA are mostly exchanged before or at the time of release of mRNA from the nucleus; the remaining mRNA-associated proteins are added in the cytoplasm, possibly in relation to cytoskeleton attachment, followed by the removal of most of these proteins during polysome formation.

Amanitins↗
PubMed1979

Changes in nitrogen balance of depleted patients with increasing infusions of glucose.

Depleted patients were maintained on intravenous infusions of amino acids and glucose with constant N intake (173 mg/kg body weight), and three different levels of energy intake (15.4, 37.6, and 58.5 kcal/kg) given sequentially for 4 days each. Changes in N balance were abrupt and maximal in 1 to 2 days. Maximal changes in N balance preceded, and were not dependent on maximal changes in fat and glucose metabolism. N retention increased 1.7 mg/kcal of increased energy balance, during both hypocaloric and hypercaloric intakes, a value similar to that observed in normal adults. No increase in resting energy expenditure occurred with increasing energy intake during negative energy balance. During positive energy balance resting energy expenditure increased by 1 kcal for each 5 of intake. It seems likely that increasing energy restores mainly that portion of lean body mass associated with fat deposition; and rapid restoration of lean body mass requires high N intakes. At zero energy balance, N balance in these depleted patients was only slightly positive at an intake of 173 mg N per kilogram. This is about twice the intake of N required to maintain zero N balance in normal adults.

Adult↗
PubMed1979

Diurnal variations in plasma concentrations of tryptophan, tryosine, and other neutral amino acids: effect of dietary protein intake.

The effect of dietary protein content on the diurnal variations in plasma neutral amino acid levels was studied in normal human subjects. For three consecutive 5-day periods, subjects consumed diets containing 0, 75, or 150 g of egg protein per day. Blood samples were drawn at 4-hr intervals on the 4th and 5th days of each period. Consumption of the protein-free diet caused plasma concentrations of all amino acids studied to fall in the late morning and afternoon, while the 150-g protein diet elicited increases in these levels during the daytime. Ingestion of the diet containing 75 g of egg protein tended to diminish the amplitudes of the daily rhythms in plasma amino acid levels, but most amino acids still exhibited small but significant elevations late in the evening. At all times of day, plasma concentrations of the large neutral amino acids studied (i.e., aromatic and branched-chain amino acids, and methionine) varied directly with the protein content of the diet. In contrast, the relationships between dietary protein content and the plasma concentrations of glycine and alanine, two small neutral amino acids, were inverse. The ratios of plasma tryptophan, tyrosine, and phenylalanine levels to the sum of the concentrations of other large neutral amino acids tended to fall as the protein content of the diet was increased. The corresponding ratio for valine increased as protein was added to the diet, while the leucine and isoleucine ratios were not correlated with dietary protein content. Since diet-induced changes in plasma trypotphan and tyrosine ratios in animals are known to cause parallel alterations in brain tryptophan and tyrosine levels, and thus in the rates of brain serotonin and catecholamine synthesis, our data suggest that ingestion of carbohydrates and protein may also normally affected brain monoamine synthesis in humans.

Adult↗
PubMed1979

Diurnal variations in plasma neutral amino acid concentrations among patients with cirrhosis: effect of dietary protein.

The effect of varying dietary protein content on the daily rhythms in plasma neutral amino acid concentrations was studied in patients with chronic cirrhosis. For two consecutive 5-day periods, subjects consumed diets containing either 0 or 75 g of protein per day. Blood samples were drawn at 4-hr intervals on the 4th and 5th days of each dietary period. For most of the neutral amino acids, the changes in plasma concentration associated with time of day or with variations in dietary protein content were similar to those observed previously in normal subjects. Ingestion of the protein-free diet caused significant reductions in the daytime level of all amino acids studied, except for tryptophan, the concentration of which did not change during the 24-hr period. Ingestion of the 75-g protein diet caused plasma levels of most of theamino acids to increase slightly during the day; these increments were not statistically significant for tryptophan, tyrosine, leucine, and methionine. The absolute plasma concentrations of most of the neutral amino acids were also in the normal range; exceptions included methonine, tyrosine, and phenylalanine, whose plasma levels were significantly elevated above normal valves. The plasma ratios of tryptophan, tyrosine, and phenylalanine concentrations to the sum of the concentrations of other large neutral amino acids increased during the day uhen the protein-free diet was ingested; this effect was moderated by the addition of protein to the food. The plasma ratios for the branched-chain amino acids were depressed below normal; those for tyrosine, phenylalanine, and methionine were significantly increased. The plasma tryptophan ratio was within the normal range. These findings provide a basis for anticipating that the uptake from blood into brain of several of the large neutral amino acids may be modified in patients with chronic cirrhosis.

Adult↗
PubMed1978

Musle protein breakdown rates in humans based on Ntau-methylhistidine (3-methylhistidine) content of mixed proteins in skeletal muscle and urinary output of Ntau-methylhistidine.

Samples of psoas muscle from nine infants (aged 1 day to 14 mo) and of several skeletal muscles from seven adult males (age 19-74 yr) were analyzed for content of protein-bound Ntau-methylhistidine (3-methylhistidine; 3-Mehis). The mean content of 3-Mehis (expressed as mumoles/g mixed protein) was 3.2 (range 2.4-3.7) in infants and 4.2 (range 3.7-4.6) in adults. The daily urinary excretion of 3-Mehis was measured in four young adult males receiving an egg-protein, flesh-free diet. Mean excretion of 3-Mehis was 211 (range 167-252) mumoles/day. From these two sets of data the mean rate of muscle protein breakdown in adult males was estimated to be 50 g/day, or 0.7 +/- 0.1 g/kg body weight/day. These results are compared with reported values for the 3-Mehis content of mixed proteins in muscle of various species, and with published estimates, computed by other techniques, of the rate of muscle protein breakdown in human subjects.

Adult↗
PubMed1978

Energy and protein intakes as determinants of nitrogen balance.

Changes in caloric intake below or above energy needs affect nitrogen balance, so that any change in caloric intake results in a corresponding alteration in nitrogen balance. The improvement in nitrogen balance caused by an increase in energy intake, however, can be frustrated if intake of protein is inadequate; conversely, the beneficial effects of an increase in protein intake can be inhibited by an inadequate energy intake. These observations mean that, in experimental studies, nitrogen balance is the result of levels of both energy and protein; in consequence, protein requirements can be interpreted only from such studies, where energy intake is also defined under the experimental conditions. In addition to the effect of dietary energy supply, dietary carbohydrate has a short-term specific effect on protein metabolism not shared by fat, in which plasma amino acids are diverted into muscle protein through the action of insulin released by the dietary carbohydrate. This metabolic interaction also occurs between carbohydrate and amino acids absorbed from the same meal.

Dietary Carbohydrates↗
PubMed1978

Urinary excretion of N gamma-methylihistidine (3-methylihistidine): a tool to study metabolic responses in relation to nutrient and hormonal status in health and disease of man.

Some of the histidine residues of actin and myosin are methylated after synthesis of these contractile muscle proteins. During breakdown of muscle protein in the course of protein turnover, the product of methylation, N gamma-methylhistidine, is released and quantitatively excreted in the urine both of rat and of man. Since most of the N gamma-methylhistidine in the body occurs in muscle, the rate of its excretion becomes a convenient measure of muscle protein breakdown. Output per kilogram of body weight is highest in the infant, especially when related to creatinine, and is reduced in the elderly as a result of loss of muscle mass with aging. A diet deficient in protein causes the young rat to have a reduced output of methylhistidine (reduced rate of muscle protein breakdown) which increases again during repletion on an adequate diet. Fasting obese human subjects also show a progressive fall in output of this metabolite. Thyroidectomy in rats reduces N gamma-methylhistidine excretion, which is only restored by giving large doses of thyroxine. On the other hand, studies on growing rats show that adrenalectomy and moderate doses of cortecosterone have no appreciable effect on the N gamma-methylhistidine output, which is only elevated by steriod administered in amounts large enough to raise plasma corticosteroid levels several-fold. These various observations show that N gamma-methylhistidine provides a useful tool in the study of muscle protein metabolic responses under a variety of nutritional and hormonal circumstances in the intact human.

Adrenal Glands↗
PubMed1978

The changing pattern of whole body protein metabolism in aging humans.

Dynamic aspects of whole body protein (nitrogen) metabolism were explored in healthy young adults and elderly men and women. Measurements were made of the rate of whole body protein breakdown, with the aid of 15N-glycine, and the rate of muscle protein breakdown, as estimated from urinary N tau-methylhistidine excretion. The results also were evaluated in relation to obligatory (endogenous) urinary nitrogen losses, previously determined in this laboratory for the two age groups. Rates of whole body and muscle protein breakdown, per unit body weight, were lower in elderly subjects than in young adults. Muscle accounted for a mean of 27% of whole body protein breakdown in young adults and 20% or less (p less than 0.01) in elderly subjects. Daily obligatory N loss was positively correlated (p less than 0.01) with whole body protein breakdown. It was calculated that muscle contributed less to the obligatory N output in elderly subjects than in young adults. These results indicate a change in the distribution of whole body protein metabolism during aging in human subjects, with muscle making a lower contribution to total body protein metabolism in elderly subjects compared with young adults.

Adolescent↗
PubMed1978

Hepatic synthesis and urinary excretion of alpha2u-globulin by male rats: diurnal rhythm and response to fasting and refeeding.

The urine of sexually mature male rats contains a protein of hepatic origin, alpha2u-globulin, not found in the urine of immature or female rats; output of this protein is greatly reduced by fasting. We have examined the effects of feeding and of fasting for various lengths of time on urinary output and hepatic synthesis of alpha2u-globulin. Rats eating ad libitum showed diurnal rhythms of urinary alpha2u-globulin excretion reaching maxima between 2000 and 0800 hours, thus coinciding with the daily feeding period of the rat. Fasting for 12 hours extinguished this diurnal rhythm. When fasting was prolonged up to 36 hours, urinary excretion of alpha2u-globulin was reduced to very low levels. Hepatic synthesis of alpha2u-globulin under these nutritional conditions was investigated by incubating liver polyribosomes with [3H]leucine and a preparation of soluble enzymes for protein synthesis and separating the labeled alpha2u-globulin peptides by immunoprecipitation followed by electrophoresis on sodium dodecyl sulfate-polyacrylamide gels. By this technique, it was shown that only membrane-bound ribosomes in the livers of mature male rats make this protein. Semi-quantitative measurement suggested that the proportion of liver polyribosomes synthesizing alpha2u-globulin was unchanged after 12 hours of fasting, but was reduced after 24 and 36 hours of fasting. It is proposed that the diurnal rhythm in alpha2u-globulin output in the urine represents translational control of its synthesis in the liver, whereas the more extensive reduction with prolonged fasting is partly due to a selective reduction in transcription of the messenger RNA for this protein.

Alpha-Globulins↗