Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of growth-suppressing and muscle-wasting treatments on muscle protein turnover and amino acid concentrations were determined in vivo. All treatments depressed protein synthesis and some treatments depressed protein breakdown. Only prolonged starvation increased protein breakdown. Muscle protein mass is regulated primarily through alterations in protein synthesis in all except emergency conditions. The increased concentrations of the branched-chain amino acids indicate that they are unlikely to be involved in this regulation.
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PMID:The relative importance of muscle protein synthesis and breakdown in the regulation of muscle mass. 13 77

The effects of starvation on tumor and host growth were studied in growing male Fischer rats bearing methylcholanthrene-induced sarcomas. Tumor growth was evaluated by changes in weight, volume, and incorporation of tritiated methyl thymidine into tumor DNA, (dpm/microgram DNA). Host growth was followed by changes in total body weight, carcass weight, and dpm/microgram liver DNA. All periods of starvation (24 to 96 hr) caused significant decreases in host body and carcass weight and dpm/microgram liver DNA. Changes in tumor weight and tumor volume in fed and starved animals were equal. Tumor dpm/microgram DNA in starved animals increased (P less than 0.005) relative to fed controls at 48, 72, and 96 hr starvation intervals. Starvation allows continued tumor growth while host wasting occurs, and is accompanied by increased tumor dpm/microgram DNA in this system.
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PMID:Nutritional manipulations and tumor growth. I. The effects of starvation. 49 46

1. Little information is currently available on protein turnover during chronic protein loss situations. We have thus measured the whole-body and tissue protein fractional synthesis rates (ks), the whole-body fractional protein degradation rate (kd), the capacity for protein synthesis (Cs) and the efficiency of protein synthesis (kRNA) in vivo in fed and fasted (1, 5 and about 9 days) 400 g rats. 2. One day of starvation resulted in a reduced ks and an increased kd in the whole body. ks was selectively depressed in skeletal muscles, mainly owing to a reduced kRNA, and was not modified in heart, liver and skin. The contribution of skin to whole-body protein synthesis increased by 39%. 3. During the phase of protein sparing (5 days of fasting), kd in the whole body decreased below the control fed level. ks in skeletal muscles was sustained because kRNA was restored to 82-98% of the control value. 4. Rats were in a protein-wasting phase after 9 days of starvation. kd in the whole body did not increase and was actually 78% of the value observed in fed animals. By contrast, ks in the whole body and tissues decreased to 14-34% of the control values, owing to reductions in both Cs and kRNA. Whatever the duration of the fast, the contribution of the skin to whole-body protein synthesis largely exceeded that of skeletal muscle. 5. The present findings suggest that the main goal in the treatment of chronic protein loss should be to sustain protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Whole-body and tissue protein synthesis during brief and prolonged fasting in the rat. 166 47

We have developed a murine model of wasting by injecting intracerebrally cells which continuously secrete h-cachectin/TNF (CHO-TNF) to: (a) determine the effects of cachectin/TNF produced continuously in the central nervous system (CNS), and (b) compare the metabolic effects of cachectin/TNF-secreting tumor in the brain to the cachexia caused by CHO-TNF tumor in peripheral tissue (IM). Intracerebral CHO-TNF tumors produced increased serum h-cachectin/TNF levels with lethal hypophagia and weight loss (mean survival time of 11 d); these changes were not observed in association with nonsecretory control brain tumors. The metabolic consequences of intracerebral cachectin/TNF production were indistinguishable from acute, lethal starvation: whole-body lipid content was decreased significantly but protein was conserved. Although intramuscular cachectin/TNF-secreting tumors caused similar increases of serum h-cachectin/TNF levels, profound anorexia did not develop; wasting developed after a longer period of tumor burden (50 d) with classical signs of cachexia (i.e., anemia and depletion of both protein and lipid). These studies provide a reproducible animal model of site-specific cytokine production and suggest that, regardless of serum levels, cachectin/TNF produced locally in brain influences both the rate of development of wasting and its net metabolic effects.
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PMID:Metabolic effects of cachectin/tumor necrosis factor are modified by site of production. Cachectin/tumor necrosis factor-secreting tumor in skeletal muscle induces chronic cachexia, while implantation in brain induces predominantly acute anorexia. 225 57

The hepatic branched-chain alpha-ketoacid dehydrogenase complex plays an important role in regulating branched-chain amino acid levels. These compounds are essential for protein synthesis but toxic if present in excess. When dietary protein is deficient, the hepatic enzyme is converted to the inactive, phosphorylated state to conserve branched-chain amino acids for protein synthesis. When dietary protein is excessive, the enzyme is in the active, dephosphorylated state to commit the excess branched-chain amino acids to degradation. Inhibition of protein synthesis by cycloheximide, even when the animal is starving for dietary protein, results in activation of the hepatic branched-chain alpha-ketoacid dehydrogenase complex to prevent accumulation of branched-chain amino acids. Likewise, the increase in branched-chain amino acids caused by body wasting during starvation and uncontrolled diabetes is blunted by activation of the hepatic branched-chain alpha-ketoacid dehydrogenase complex. The activity state of the complex is regulated in the short term by the concentration of branched-chain alpha-ketoacids (inhibitors of branched-chain alpha-ketoacid dehydrogenase kinase) and in the long term by alteration in total branched-chain alpha-ketoacid dehydrogenase kinase activity. cDNAs have been cloned and the primary structure of the mature proteins deduced for the E1 alpha subunit of the human and rat liver branched-chain alpha-ketoacid dehydrogenase complex. The cDNA and protein sequences are highly conserved for the two species. Considerable sequence similarity is also apparent between the E1 alpha subunits of the human branched-chain alpha-ketoacid dehydrogenase complex and the pyruvate dehydrogenase complex. Maple syrup urine disease is caused by an inherited deficiency in the branched-chain alpha-ketoacid dehydrogenase complex. The molecular basis of one maple syrup urine disease family has been determined for the first time. The patient was found to be a compound heterozygote, inheriting an allele encoding an abnormal E1 alpha from the father, and an allele which is not expressed from the mother. The only known animal model for the disease (Polled Hereford cattle) has also been characterized. The mutation in these animals introduces a stop codon in the leader peptide of the E1 alpha subunit, resulting in premature termination of translation. Two thiamine responsive patients have been studied. The deduced amino acid sequences of the mature E1 alpha subunit and its leader sequence were normal, suggesting that the defect in these patients must exist in some other subunit of the complex. 3-Hydroxyisobutyrate dehydrogenase and methylmalonate-semialdehyde dehydrogenase, two enzymes of the valine catabolic pathway, were purified from liver tissue and characterized.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Regulation of the branched-chain alpha-ketoacid dehydrogenase and elucidation of a molecular basis for maple syrup urine disease. 240 34

Malnutrition is a common complicating factor in surgical illness. To investigate the cellular changes and mechanisms responsible for the protein wasting associated with nutritional deprivation, Sprague-Dawley rats were subjected to total protein-calorie starvation for 3 (n = 12) or 5 days (n = 12) and compared to freely fed animals monitored for 3 (n = 8) or 5 (n = 8) days. Gastrocnemius protein and RNA content and levels of mRNA coding for the myofibrillar proteins myosin heavy chain, myosin light chain, and alpha-actin were measured. Starvation resulted in a significant decrease in gastrocnemius mass and protein content, and was associated with decreases in mRNA levels for the three myofibrillar proteins assayed. We conclude that changes in mRNA levels for these proteins likely contribute to the loss of peripheral protein which occurs during total nutritional deprivation. In addition, the changes in mRNA levels for these three structural proteins appear to be coordinate, suggesting that transcription of no single myofibrillar protein is rate-limiting in the regulation of skeletal muscle protein content.
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PMID:Starvation leads to decreased levels of mRNA for myofibrillar proteins. 249 68

The hepatic branched-chain alpha-keto acid dehydrogenase complex plays an important role in regulating branched-chain amino acid levels. These compounds are essential for protein synthesis but are toxic if present in excess. When dietary protein is deficient, the hepatic enzyme is present in the inactive, phosphorylated state to allow conservation of branched-chain amino acids for protein synthesis. When dietary protein is excessive, the enzyme is in the active, dephosphorylated state to commit the excess branched-chain amino acids to degradation. Inhibition of protein synthesis by cycloheximide, even when the animal is starving for protein, results in activation of the hepatic branched-chain alpha-keto acid dehydrogenase complex to prevent accumulation of branched-chain amino acids. Likewise, the increase in branched-chain amino acids caused by body wasting during starvation and uncontrolled diabetes is blunted by activation of the hepatic branched-chain alpha-keto acid dehydrogenase complex. The activity state of the hepatic branched-chain alpha-keto acid dehydrogenase complex is regulated in the short term by the concentration of branched-chain alpha-keto acids (inhibitors of branched-chain alpha-keto acid dehydrogenase kinase) and in the long term by alteration in the total branched chain alpha-keto acid dehydrogenase kinase activity.
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PMID:Nutritional and hormonal regulation of the activity state of hepatic branched-chain alpha-keto acid dehydrogenase complex. 263 49

The peripheral nitrogen wasting and loss of functional capacity caused by the malnutrition of disease and the immobilization of hospitalization may not be readily reversed by refeeding alone. In order to examine submaximal exercise as an adjunctive anabolic stimulus to intravenous refeeding (IVF) in depleted subjects, 14 volunteers were studied in the postabsorptive (PA) state, after 10 days of total starvation, and again after 10 days of nutritional repletion with I.V. feedings. The subjects were randomized to one group that received IVF alone and one group that performed 1 hour of submaximal (51% of VO2max) stationary bicycle exercise daily during IVF. The exercised group was not significantly different from the nonexercised group in urinary nitrogen balance, resting energy expenditure, extremity amino acid flux, or maximal oxygen consumption. Acute exercise did not induce significant derangements in electrolytes or counter-regulatory hormone concentrations. Ten days of submaximal exercise does not appear to be detrimental in this population recovering from moderate hospitalized malnutrition, but additional anabolic stimulae may be needed for improvements in protein accrual or functional capacity.
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PMID:Submaximal exercise during intravenous hyperalimentation of depleted subjects. 312

Evidence for muscle protein wasting and abnormal muscle metabolism is common in uremia. Muscle DNA content is considered a reliable reference standard in normal and undernourished adults. Muscle RNA content rapidly changes during starvation and refeeding. The ratio of noncollagen alkali-soluble proteins (ASP) to DNA is considered to be an estimate of the cytoplasmic volume of a single cell, and the RNA: DNA ratio is an index of the ribosomal capacity for protein synthesis. Muscle DNA, RNA, ASP, water, and fat content were determined in muscle biopsy specimens from chronically uremic patients receiving conservative treatment (CT), maintenance hemodialysis (two centers), or CAPD. Nutrient intake was low and the anthropometric indices were decreased in all groups of patients, except in the hemodialysis patients from one center. Serum proteins and muscle ASP: DNA and RNA: DNA ratios were decreased. The nutritional status was reassessed in some malnourished CAPD patients after about one year of careful nutritional advice and was unchanged. These results suggest that chronically uremic patients on CT are often malnourished, primarily because of an inadequate protein and/or energy intake. Muscle nucleic acid and protein content are useful tools for nutritional assessment at a cellular level in humans with chronic renal failure and can be used to monitor the response to nutritional therapy.
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PMID:Muscle biopsy studies in chronically uremic patients: evidence for malnutrition. 620

Protein degradation was measured as tyrosine release rate from proteins of extensor digitorum longus (EDL) muscles and as urinary excretion of 3-methylhistidine in freely fed adult nongrowing C57BL/6J mice with sarcomas, to study protein degradation in cancer-induced wasting of skeletal muscles. Whole muscle protein breakdown rate was unchanged, whereas protein synthesis was depressed, leading to an increased net degradation of skeletal muscles with loss of soluble, myofibrillar, and collagen proteins. Starvation for 24 hours elevated whole muscle protein breakdown in mice with and without sarcomas. Subsequent refeeding for 24 hours normalized the degradation. Adaptation to anorexia in pair-fed controls was achieved by a decrease in muscle protein turnover evaluated by urinary excretion of 3-methylhistidine over 5 days. The measurement of "catabolic decrease" of muscle protein breakdown protected the muscle mass in mice without tumors, but it was ineffective in tumor-bearing animals. The unchanged rate of breakdown of proteins in whole EDL muscles from tumor-bearing mice was accompanied by increased maximum cathepsin D activity and by elevated autolytic activity at acid pH in some muscles. Therefore, cathepsin D activity and net protease activities did not reflect whole muscle protein degradation in tumor-induced malnutrition. The results demonstrate that wasting of skeletal muscles in experimental cancer was not dependent on increased degradation but was dependent on depressed protein synthesis.
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PMID:Lack of evidence for elevated breakdown rate of skeletal muscles in weight-losing, tumor-bearing mice. 657 91


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