This article provides a comprehensive review and explores the gaps in current knowledge of lysine metabolism in humans and its potential nutritional and therapeutic indications. The first part of this study examines lysine sources, requirements, transport through the plasma membrane, lysine catabolism, and its disorders. The central part is focused on post-translational modifications of lysine in proteins, primarily desmosine formation in elastin, hydroxylation in collagen, covalent bonds with glutamine, methylation, ubiquitination, sumoylation, neddylation, acylation, lactylation, carbamylation, and glycation. Special sections are devoted to using lysine as a substrate for homoarginine and carnitine synthesis and in nutrition and medicine. It is concluded that the identification and detailed knowledge of writers, readers, and erasers of specific post-translational modifications of lysine residues in proteins is needed for a better understanding of the role of lysine in epigenetic regulation. Further research is required to explore the influence of lysine availability on homoarginine formation and how the phenomenon of lysine-arginine antagonism can be used to influence immune and cardiovascular functions and cancer development. Of unique importance is the investigation of the use of lysine in osteoporosis therapy and in reducing the resorption of harmful substances in the kidneys, as well as the therapeutic potential of polylysine and lysine analogs.

• Keywords
• cadaverine, carnitine, desmosine, homoarginine, homocitrulline, lysine–arginine antagonism, saccharopine,
• MeSH
• Humans MeSH
• Lysine * metabolism   MeSH
• Protein Processing, Post-Translational MeSH
• Dietary Supplements * MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Lysine * MeSH

Aspartic acid exists in L- and D-isoforms (L-Asp and D-Asp). Most L-Asp is synthesized by mitochondrial aspartate aminotransferase from oxaloacetate and glutamate acquired by glutamine deamidation, particularly in the liver and tumor cells, and transamination of branched-chain amino acids (BCAAs), particularly in muscles. The main source of D-Asp is the racemization of L-Asp. L-Asp transported via aspartate-glutamate carrier to the cytosol is used in protein and nucleotide synthesis, gluconeogenesis, urea, and purine-nucleotide cycles, and neurotransmission and via the malate-aspartate shuttle maintains NADH delivery to mitochondria and redox balance. L-Asp released from neurons connects with the glutamate-glutamine cycle and ensures glycolysis and ammonia detoxification in astrocytes. D-Asp has a role in brain development and hypothalamus regulation. The hereditary disorders in L-Asp metabolism include citrullinemia, asparagine synthetase deficiency, Canavan disease, and dicarboxylic aminoaciduria. L-Asp plays a role in the pathogenesis of psychiatric and neurologic disorders and alterations in BCAA levels in diabetes and hyperammonemia. Further research is needed to examine the targeting of L-Asp metabolism as a strategy to fight cancer, the use of L-Asp as a dietary supplement, and the risks of increased L-Asp consumption. The role of D-Asp in the brain warrants studies on its therapeutic potential in psychiatric and neurologic disorders.

• Keywords
• aspartame, aspartate and cell-to-cell interactions, branched-chain amino acids, gluconeogenesis, glutamate–glutamine cycle, malate–aspartate shuttle, neurotransmission, oxaloacetate, purine-nucleotide cycle, urea cycle,
• Publication type
• Journal Article MeSH
• Review MeSH

Aspartate-glutamate carrier 2 (AGC2, citrin) is a mitochondrial carrier expressed in the liver that transports aspartate from mitochondria into the cytosol in exchange for glutamate. The AGC2 is the main component of the malate-aspartate shuttle (MAS) that ensures indirect transport of NADH produced in the cytosol during glycolysis, lactate oxidation to pyruvate, and ethanol oxidation to acetaldehyde into mitochondria. Through MAS, AGC2 is necessary to maintain intracellular redox balance, mitochondrial respiration, and ATP synthesis. Through elevated cytosolic Ca2+ level, the AGC2 is stimulated by catecholamines and glucagon during starvation, exercise, and muscle wasting disorders. In these conditions, AGC2 increases aspartate input to the urea cycle, where aspartate is a source of one of two nitrogen atoms in the urea molecule (the other is ammonia), and a substrate for the synthesis of fumarate that is gradually converted to oxaloacetate, the starting substrate for gluconeogenesis. Furthermore, aspartate is a substrate for the synthesis of asparagine, nucleotides, and proteins. It is concluded that AGC2 plays a fundamental role in the compartmentalization of aspartate and glutamate metabolism and linkage of the reactions of MAS, glycolysis, gluconeogenesis, amino acid catabolism, urea cycle, protein synthesis, and cell proliferation. Targeting of AGC genes may represent a new therapeutic strategy to fight cancer. [BMB Reports 2023; 56(7): 385-391].

• MeSH
• Glucose * metabolism   MeSH
• Liver metabolism   MeSH
• Aspartic Acid * metabolism   MeSH
• Glutamic Acid metabolism   MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• aspartate-glutamate carrier MeSH Browser
• citrin MeSH Browser
• Glucose * MeSH
• Aspartic Acid * MeSH
• Glutamic Acid MeSH

The aim of the article is to examine side effects of increased dietary intake of amino acids, which are commonly used as a dietary supplement. In addition to toxicity, mutagenicity and carcinogenicity, attention is focused on renal and gastrointestinal tract functions, ammonia production, and consequences of a competition with other amino acids for a carrier at the cell membranes and enzymes responsible for their degradation. In alphabetic order are examined arginine, beta-alanine, branched-chain amino acids, carnosine, citrulline, creatine, glutamine, histidine, beta -hydroxy- beta -methylbutyrate, leucine, and tryptophan. In the article is shown that enhanced intake of most amino acid supplements may not be risk-free and can cause a number of detrimental side effects. Further research is necessary to elucidate effects of high doses and long-term consumption of amino acid supplements on immune system, brain function, muscle protein balance, synthesis of toxic metabolites, and tumor growth and examine their suitability under certain circumstances. These include elderly, childhood, pregnancy, nursing a baby, and medical condition, such as diabetes and liver disease. Studies are also needed to examine adaptive response to a long-term intake of any substance and consequences of discontinuation of supplementation.

• MeSH
• Amino Acids adverse effects   metabolism   MeSH
• Arginine pharmacology   MeSH
• Child MeSH
• Glutamine * metabolism   pharmacology   MeSH
• Histidine metabolism   MeSH
• Muscle, Skeletal metabolism   MeSH
• Humans MeSH
• Dietary Supplements * adverse effects   MeSH
• Aged MeSH
• Pregnancy MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Aged MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Amino Acids MeSH
• Arginine MeSH
• Glutamine * MeSH
• Histidine MeSH