Metabolic rewiring is a characteristic hallmark of cancer cells. This phenomenon sustains uncontrolled proliferation and resistance to apoptosis by increasing nutrients and energy supply. However, reprogramming comes together with vulnerabilities that can be used against tumor and can be applied in targeted therapy. In the last years, the genetic background of tumors has been identified thoroughly and new therapies targeting those mutations tested. Nevertheless, we propose that targeting the phenotype of cancer cells could be another way of treatment aiming to avoid drug resistance and non-responsiveness of cancer patients. Amino acid metabolism is part of the altered processes in cancer cells. Amino acids are building blocks and also sensors of signaling pathways regulating main biological processes. In this comprehensive review, we described four amino acids (asparagine, arginine, methionine, and cysteine) which have been actively investigated as potential targets for anti-tumor therapy. Asparagine depletion is successfully used for decades in the treatment of acute lymphoblastic leukemia and there is a strong implication to apply it to other types of tumors. Arginine auxotrophic tumors are great candidates for arginine-starvation therapy. Higher requirement for essential amino acids such as methionine and cysteine point out promising targetable weaknesses of cancer cells.

• Klíčová slova
• Amino acid metabolism, Arginine, Asparagine, Cancer, Cysteine, Methionine, Targeted therapy,
• MeSH
• aminokyseliny metabolismus   MeSH
• arginin metabolismus   terapeutické užití   MeSH
• asparagin * metabolismus   terapeutické užití   MeSH
• cystein metabolismus   MeSH
• lidé MeSH
• methionin MeSH
• nádory * metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• aminokyseliny MeSH
• arginin MeSH
• asparagin * MeSH
• cystein MeSH
• methionin MeSH

The metabolism of sulfur-containing amino acids (SAAs) requires an orchestrated interplay among several dozen enzymes and transporters, and an adequate dietary intake of methionine (Met), cysteine (Cys), and B vitamins. Known human genetic disorders are due to defects in Met demethylation, homocysteine (Hcy) remethylation, or cobalamin and folate metabolism, in Hcy transsulfuration, and Cys and hydrogen sulfide (H2S) catabolism. These disorders may manifest between the newborn period and late adulthood by a combination of neuropsychiatric abnormalities, thromboembolism, megaloblastic anemia, hepatopathy, myopathy, and bone and connective tissue abnormalities. Biochemical features include metabolite deficiencies (e.g. Met, S-adenosylmethionine (AdoMet), intermediates in 1-carbon metabolism, Cys, or glutathione) and/or their accumulation (e.g. S-adenosylhomocysteine, Hcy, H2S, or sulfite). Treatment should be started as early as possible and may include a low-protein/low-Met diet with Cys-enriched amino acid supplements, pharmacological doses of B vitamins, betaine to stimulate Hcy remethylation, the provision of N-acetylcysteine or AdoMet, or experimental approaches such as liver transplantation or enzyme replacement therapy. In several disorders, patients are exposed to long-term markedly elevated Met concentrations. Although these conditions may inform on Met toxicity, interpretation is difficult due to the presence of additional metabolic changes. Two disorders seem to exhibit Met-associated toxicity in the brain. An increased risk of demyelination in patients with Met adenosyltransferase I/III (MATI/III) deficiency due to biallelic mutations in the MATIA gene has been attributed to very high blood Met concentrations (typically >800 μmol/L) and possibly also to decreased liver AdoMet synthesis. An excessively high Met concentration in some patients with cystathionine β-synthase deficiency has been associated with encephalopathy and brain edema, and direct toxicity of Met has been postulated. In summary, studies in patients with various disorders of SAA metabolism showed complex metabolic changes with distant cellular consequences, most of which are not attributable to direct Met toxicity.

• Klíčová slova
• S-adenosylhomocysteine hydrolase deficiency, adenosine kinase deficiency, cystathionine β-synthase deficiency, ethylmalonic encephalopathy, glycine N-methyltransferase deficiency, homocystinuria, methionine adenosyltransferase I/III deficiency, methionine restricted diet, remethylation defects, sulfite oxidase deficiency,
• MeSH
• aminokyseliny sírové metabolismus   MeSH
• cystein metabolismus   MeSH
• glutathion metabolismus   MeSH
• homocystein metabolismus   MeSH
• homocystinurie etiologie   metabolismus   MeSH
• játra metabolismus   MeSH
• lidé MeSH
• metabolické nemoci genetika   metabolismus   patologie   terapie   MeSH
• methionin metabolismus   MeSH
• methioninadenosyltransferasa metabolismus   MeSH
• metylace MeSH
• nemoci mozku etiologie   metabolismus   MeSH
• S-adenosylmethionin metabolismus   MeSH
• síra metabolismus   MeSH
• siřičitany metabolismus   MeSH
• sloučeniny síry metabolismus   MeSH
• sulfan metabolismus   MeSH
• vrozené poruchy metabolismu patologie   terapie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• aminokyseliny sírové MeSH
• cystein MeSH
• glutathion MeSH
• homocystein MeSH
• methionin MeSH
• methioninadenosyltransferasa MeSH
• S-adenosylmethionin MeSH
• síra MeSH
• siřičitany MeSH
• sloučeniny síry MeSH
• sulfan MeSH

Naturally occurring secondary amino acids, with proline as the main representative, contain an alpha-imino group in a cycle that is typically four-, five-, and six-membered. The unique ring structure exhibits exceptional properties-conformational rigidity, chemical stability, and specific roles in protein structure and folding. Many proline analogues have been used as valuable compounds for the study of metabolism of both prokaryotic and eukaryotic cells and for the synthesis of compounds with desired biological, pharmaceutical, or industrial properties. The D-forms of secondary amino acids play different roles in living organisms than the L-forms. They have different metabolic pathways, biological, physiological, and pharmacological effects, they can be indicators of changes and also serve as biomarkers of diseases. In the scientific literature, the number of articles examining D-amino acids in biological samples is increasing. The review summarises information on the occurrence and importance of D- and L-secondary amino acids-azetidic acid, proline, hydroxyprolines, pipecolic, nipecotic, hydroxypipecolic acids and related peptides containing these D-AAs, as well as the main analytical methods (mostly chromatographic) used for their enantiomeric determination in different matrices (biological samples, plants, food, water, and soil).

• Klíčová slova
• Chiral analysis, D- and L-secondary amino acids, Enantiomers, Imino acids, Proline analogues,
• MeSH
• aminokyseliny * chemie   MeSH
• iminokyseliny * chemie   MeSH
• peptidy MeSH
• prolin chemie   MeSH
• stereoizomerie MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• aminokyseliny * MeSH
• iminokyseliny * MeSH
• peptidy MeSH
• prolin MeSH

L-serine plays an essential role in a broad range of cellular functions including protein synthesis, neurotransmission, and folate and methionine cycles and synthesis of sphingolipids, phospholipids, and sulphur containing amino acids. A hydroxyl side-chain of L-serine contributes to polarity of proteins, and serves as a primary site for binding a phosphate group to regulate protein function. D-serine, its D-isoform, has a unique role. Recent studies indicate increased requirements for L-serine and its potential therapeutic use in some diseases. L-serine deficiency is associated with impaired function of the nervous system, primarily due to abnormal metabolism of phospholipids and sphingolipids, particularly increased synthesis of deoxysphingolipids. Therapeutic benefits of L-serine have been reported in primary disorders of serine metabolism, diabetic neuropathy, hyperhomocysteinemia, and amyotrophic lateral sclerosis. Use of L-serine and its metabolic products, specifically D-serine and phosphatidylserine, has been investigated for the therapy of renal diseases, central nervous system injury, and in a wide range of neurological and psychiatric disorders. It is concluded that there are disorders in which humans cannot synthesize L-serine in sufficient quantities, that L-serine is effective in therapy of disorders associated with its deficiency, and that L-serine should be classified as a "conditionally essential" amino acid.

• Klíčová slova
• deoxysphingolipids, diabetes, glycine, hyperhocysteinemia, neuropathy, serine supplementation,
• MeSH
• esenciální aminokyseliny MeSH
• fosfolipidy MeSH
• lidé MeSH
• serin * MeSH
• sfingolipidy metabolismus   MeSH
• vrozené poruchy metabolismu aminokyselin * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• esenciální aminokyseliny MeSH
• fosfolipidy MeSH
• serin * MeSH
• sfingolipidy MeSH

• Klíčová slova
• AMINO ACIDS/metabolism *,
• MeSH
• aminokyseliny metabolismus   MeSH
• antifibrinolytika * MeSH
• biochemické jevy * MeSH
• bioreaktory * MeSH
• fermentace * MeSH
• molekulová hmotnost * MeSH
• Streptomyces * MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aminokyseliny MeSH
• antifibrinolytika * MeSH

Decarboxylation of aromatic amino acid in mammalian tissues is catalyzed by aromatic amino acid decarboxylase (EC. 4.1.1.28, AAD). The enzyme differs in its affinity to individual aromatic amino acids, the best substrates being 3,4-dihydroxyphenylalanine (dopa) and 5-hydroxytroptophan. Surprisingly, AAD is abundant in the liver, where the substrates with rather low affinity to AAD as tryptophan, phenylalanine, and tyrosine are offered to decarboxylation. In the present paper, the possibility of interference of tryptophan with decarboxylation of phenylalanine, tyrosine as well as dopa in the liver was investigated. The AAD activity was measured radiometrically with 1-14C-labeled aromatic amino acid substrates using the rat liver enzyme. The influence of tryptophan on decarboxylation of tyrosine was formally competitive with Ki = 9.2 x 10(-3) M, while the inhibition of decarboxylation of phenylalanine by tryptophan was non-competitive with Ki at 2.75 x 10(-2) M. The effect of tryptophan on decarboxylation of dopa was small and it could not be expressed in terms of inhibition kinetics and inhibition constant. At physiological concentrations of aromatic amino acids in plasma, tryptophan does not seem to have remarkable effects on decarboxylation of phenylalanine, tyrosine, and dopa in the liver.

• MeSH
• aminokyseliny metabolismus   MeSH
• dekarboxylasy aromatických L-aminokyselin metabolismus   MeSH
• dihydroxyfenylalanin metabolismus   MeSH
• fenylalanin metabolismus   MeSH
• játra metabolismus   MeSH
• krysa rodu Rattus MeSH
• potkani Wistar MeSH
• techniky in vitro MeSH
• tryptofan farmakologie   MeSH
• tyrosin metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aminokyseliny MeSH
• dekarboxylasy aromatických L-aminokyselin MeSH
• dihydroxyfenylalanin MeSH
• fenylalanin MeSH
• tryptofan MeSH
• tyrosin MeSH

Metabolic reprogramming of cancer cells is a common hallmark of malignant transformation. The preference for aerobic glycolysis over oxidative phosphorylation in tumors is a well-studied phenomenon known as the Warburg effect. Importantly, metabolic transformation of cancer cells also involves alterations in signaling cascades contributing to lipid metabolism, amino acid flux and synthesis, and utilization of ketone bodies. Also, redox regulation interacts with metabolic reprogramming during malignant transformation. Flavonoids, widely distributed phytochemicals in plants, exert various beneficial effects on human health through modulating molecular cascades altered in the pathological cancer phenotype. Recent evidence has identified numerous flavonoids as modulators of critical components of cancer metabolism and associated pathways interacting with metabolic cascades such as redox balance. Flavonoids affect lipid metabolism by regulating fatty acid synthase, redox balance by modulating nuclear factor-erythroid factor 2-related factor 2 (Nrf2) activity, or amino acid flux and synthesis by phosphoglycerate mutase 1. Here, we discuss recent preclinical evidence evaluating the impact of flavonoids on cancer metabolism, focusing on lipid and amino acid metabolic cascades, redox balance, and ketone bodies.

• Klíčová slova
• Cancer cells, Carcinogenesis, Flavonoids, Metabolic reprogramming, Metabolism,
• MeSH
• aminokyseliny * MeSH
• faktor 2 související s NF-E2 metabolismus   MeSH
• flavonoidy farmakologie   MeSH
• ketolátky metabolismus   MeSH
• lidé MeSH
• metabolismus lipidů MeSH
• nádorová transformace buněk metabolismus   MeSH
• nádory * farmakoterapie   metabolismus   MeSH
• oxidace-redukce MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• aminokyseliny * MeSH
• faktor 2 související s NF-E2 MeSH
• flavonoidy MeSH
• ketolátky MeSH

The branched-chain amino acids (BCAAs; valine, isoleucine, and leucine) are the major nitrogen source for glutamine and alanine synthesis in muscle. Synthesis of glutamine, alanine, and BCAA use is activated in critical illnesses such as in sepsis, cancer, and trauma. The use of glutamine often exceeds its synthesis, resulting in the lack of glutamine in plasma and tissues. In critical illness, resynthesis of BCAA from branched-chain keto acids is activated, particularly in hepatic tissue. The BCAA released to circulation may be used for protein synthesis or synthesis of alanine and glutamine. Glutamine and/or alanine infusion has an inhibitory effect on the breakdown of body proteins and decreases BCAA catabolism in postabsorptive control, endotoxemic, and irradiated rats. Decreased protein breakdown also was observed when glutamine synthesis was activated by ammonia infusion. In conclusion some favorable effects of BCAA supply can be explained by its role in the synthesis of glutamine and some positive effects of glutamine exogenous supply can be explained by its effect on metabolism of BCAA.

• MeSH
• alanin biosyntéza   metabolismus   MeSH
• glutamin biosyntéza   metabolismus   MeSH
• játra metabolismus   MeSH
• kosterní svaly metabolismus   MeSH
• kritický stav MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• proteiny metabolismus   MeSH
• větvené aminokyseliny metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• alanin MeSH
• glutamin MeSH
• proteiny MeSH
• větvené aminokyseliny MeSH

The aim of this study was to find some relationship between amino acid metabolism and the embryo morphokinetic parameters studied via time-lapse analysis. Study included 48 human embryo samples and their culture media. Two groups of embryos were identified: embryos reached the 8-cell stage on day 3 (n=34) and embryos failed to develop at any point during the incubation (n=14). Amino acids levels were measured on day 3 of embryo development; using time-lapse analysis, the precise timing of embryo cleavage, synchrony of division, grade of fragmentation etc. were established. No statistically significant differences between dividing and arresting embryos were observed in terms of amino acids production/consumption and turnover. Amino acids which were part of the culture medium did not exhibit any statistically significant correlation with kinetic parameters with the exception of the grade of fragmentation on day 3; there were negative correlation with glutamate, and positive with glutamine, glycine and taurine. In some dividing and in some arresting embryos appeared new amino acids which strongly correlated with each other, with methionine, but not with any other amino acid that is a regular part of the culture medium.

• MeSH
• aminokyseliny metabolismus   MeSH
• embryo savčí metabolismus   MeSH
• embryonální vývoj * MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• aminokyseliny MeSH

So far multiple differences in prostate cancer-specific amino acids metabolism have been discovered. Moreover, attempts to utilize these alterations for prostate cancer diagnosis and treatment have been made. The prostate cancer metabolism and biosynthesis of amino acids are particularly focused on anaplerosis more than on energy production. Other crucial requirements on amino acids pool come from the serine, one‑carbon cycle, glycine synthesis pathway and folate metabolism forming major sources of interproducts for synthesis of nucleobases necessary for rapidly proliferating cells. Considering the lack of some amino acids biosynthetic pathways and/or their extraordinary importance for prostate cancer cells, there is a widespread potential for targeted therapeutic applications with no effect on non-malignant cells. This review summarizes the up-to-date knowledge of the importance of amino acids for prostate cancer pathogenesis with a special emphasis on potential applications of metabolic variabilities in the new oncologic paradigm of precision medicine.

• Klíčová slova
• Mitochondria, Personalized medicine, Prostate, Sarcosine, Serine, Warburg effect,
• MeSH
• aminokyseliny metabolismus   MeSH
• individualizovaná medicína * MeSH
• lidé MeSH
• nádory prostaty metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• aminokyseliny MeSH