Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0235394 (wasting)
 8,040 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amino acids contained in proteins can be transformed either in glucose precursors or in acetate, the end product of free fatty acid (FFA) oxidation. The dynamics of glucose, FFA, and amino acid competition for entry into the citric acid cycle (tricarboxylic acid [TCA] cycle) are very complex and not fully understood. Conditions where glucose is insufficiently driven to full oxidation are characterized by lowest efficiency in energy production per mole of oxygen consumed. Moreover, acetate provided by oxidation of FFA increases consumption of amino acids as precursors of the oxaloacetate required for condensation with acetate and for maintenance of citrate synthesis. Increased consumption of amino acids in the TCA cycle, if not matched by adequate intake, leads to muscular wasting and cachexia. Therefore, amino acid needs are very complex, and their intake must provide a balanced ratio of glucogenic and ketogenic precursors suitable to trigger entry of glucose to full oxidation and blunt the level of FFA utilization. Optimization of substrate entry into energy production must also be coupled with sufficient availability of amino acids in ratios suitable for maintaining protein synthesis, inhibiting the catabolic drive, and promoting integrity of cellular proteic structures. Alimentary proteins have a content of amino acids that is far from the stoichiometric ratios of essential amino acids required by humans. An amino acid formulation suitable to match energy needs, control carbohydrate and lipid flow into the TCA cycle, and promote protein synthesis in contracting cells is detailed in this article.
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PMID:Wasting and the substrate-to-energy controlled pathway: a role for insulin resistance and amino acids. 1509 98

Chronic kidney disease (CKD) leads to decreased sensitivity to the metabolic effects of insulin, contributing to protein energy wasting and muscle atrophy. Targeted metabolomics profiling during hyperinsulinemic-euglycemic insulin clamp testing may help identify aberrant metabolic pathways contributing to insulin resistance in CKD. Using targeted metabolomics profiling, we examined the plasma metabolome in 95 adults without diabetes in the fasted state (58 with CKD, 37 with normal glomerular filtration rate [GFR]) who underwent hyperinsulinemic-euglycemic clamp. We assessed heterogeneity in fasting metabolites and the response to insulin to identify potential metabolic pathways linking CKD with insulin resistance. Baseline differences and effect modification by CKD status on changes with insulin clamp testing were adjusted for confounders. Mean GFR among participants with CKD was 37.3 compared with 89.3 ml/min per 1.73 m2 among controls. Fasted-state differences between CKD and controls included abnormalities in tryptophan metabolism, ubiquinone biosynthesis, and the TCA cycle. Insulin infusion markedly decreased metabolite levels, predominantly amino acids and their metabolites. CKD was associated with attenuated insulin-induced changes in nicotinamide, arachidonic acid, and glutamine/glutamate metabolic pathways. Metabolomics profiling suggests disruption in amino acid metabolism and mitochondrial function as putative manifestations or mechanisms of the impaired anabolic effects of insulin in CKD.
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PMID:Chronic kidney disease attenuates the plasma metabolome response to insulin. 3013 9