Emerging Insights into the Relationship Between Amino Acid Metabolism and Diabetic Cardiomyopathy

Figures

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  Figure 1. Pathways of amino acid metabolism. Most amino acids undergo catabolic processes in the liver, primarily through deamination to form α-keto acids and ammonia (NH3/NH4+). The resulting α-keto acids are oxidized in the mitochondria for energy production, converted into glucose and fatty acids, or resynthesized into NEAAs. Ammonia is predominantly detoxified via the ornithine cycle to form urea and ultimately excreted by the kidneys. Moreover, certain amino acids can be decarboxylated to yield carbon dioxide and amines. The arrows in the figure represent either the transport of substances or the course of biochemical processes.

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  Figure 2. Regulation of amino acid metabolic enzymes. Enzymes involved in amino acid metabolism are regulated by a variety of factors. Bioactive compounds in food, such as quercetin and organic acids, can inhibit or activate the activity of different digestive enzymes. Cofactor dysfunction may lead to impaired enzyme activity and disease pathogenesis. In addition, the transcription of enzymes is regulated by factors such as diet, the gut microbiota, hormone levels, and transcription factors. + and − represent the activation and inhibition of digestive enzyme activity, respectively.

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  Figure 3. Branched-Chain Amino Acids Metabolism in DCM. Under physiological conditions, BCAAs undergo catabolism via a series of enzymatic reactions in the mitochondria of skeletal muscle, myocardium, and hepatic tissues. In diabetes, the interplay of impaired glucose/lipid metabolism, vagal dysfunction, and gut microbiota disruption alters the status of substrates and enzymes within the myocardial BCAA metabolic pathway, which contributes to the pathogenesis of DCM. Mechanistically, autophagy dysregulation, oxidative stress, and inflammatory responses collectively drive myocardial hypertrophy and fibrosis, ultimately manifesting as impaired cardiac function. An upward arrow indicates an increase in a substance or the promotion of a biological process, while a downward arrow indicates a decrease in a substance or the inhibition of a biological process.