Novel Biosynthesis, Metabolism and Physiological Functions of L-Homoarginine

Adams, Sam; Che, Dongsheng; Qin, Guixin; Farouk, Mohammed Hamdy; Jiang, Hongrui; Han, Rui

doi:10.2174/1389203719666181026170049

Cited by 29 publications

(37 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this regard, the pregnancy-induced changes in metabolic correlations of cerebellar lysine are of interest, because gestational diabetes is associated with plasma levels of lysine and tyrosine [54], both of them correlating to each other much stronger in cerebellum of the pregnant than non-pregnant rats (Table 3). Besides, lysine catabolism is related to biosynthesis of homoarginine which is elevated in normal pregnancy [13], with some studies linking its elevation to pregnancy disorders, including preeclampsia [55]. Physiological manifestations of pre-eclampsia and eclampsia, associated with nearly one-tenth of all maternal deaths [56], involve changed cerebral hemodynamics and hypertensive encephalopathy [57][58][59], potentially linked to impaired signaling by homoarginine, known as a predictor of cardiovascular risk and mortality [3].…”

Section: Discussionmentioning

confidence: 99%

Hypoxic Adaptation of Mitochondrial Metabolism in Rat Cerebellum Decreases in Pregnancy

Граф

Trofimova

Ksenofontov

et al. 2020

Cells

View full text Add to dashboard Cite

Function of brain amino acids as neurotransmitters or their precursors implies changes in the amino acid levels and/or metabolism in response to physiological and environmental challenges. Modelling such challenges by pregnancy and/or hypoxia, we characterize the amino acid pool in the rat cerebellum, quantifying the levels and correlations of 15 amino acids and activity of 2-oxoglutarate dehydrogenase complex (OGDHC). The parameters are systemic indicators of metabolism because OGDHC limits the flux through mitochondrial TCA cycle, where amino acids are degraded and their precursors synthesized. Compared to non-pregnant state, pregnancy increases the cerebellar content of glutamate and tryptophan, decreasing interdependence between the quantified components of amino acid metabolism. In response to hypoxia, the dependence of cerebellar amino acid pool on OGDHC and the average levels of arginine, glutamate, lysine, methionine, serine, phenylalanine, and tryptophan increase in non-pregnant rats only. This is accompanied by a higher hypoxic resistance of the non-pregnant vs. pregnant rats, pointing to adaptive significance of the hypoxia-induced changes in the cerebellar amino acid metabolism. These adaptive mechanisms are not effective in the pregnancy-changed metabolic network. Thus, the cerebellar amino acid levels and OGDHC activity provide sensitive markers of the physiology-dependent organization of metabolic network and its stress adaptations.

show abstract

Section: Discussionmentioning

confidence: 99%

Hypoxic Adaptation of Mitochondrial Metabolism in Rat Cerebellum Decreases in Pregnancy

Граф

Trofimova

Ksenofontov

et al. 2020

Cells

View full text Add to dashboard Cite

show abstract

“…In addition to the 2-AAA pathway of lysine degradation, L-homoarginine may be also synthesized from lysine catabolism and, this alternative pathway, involving arginine and nitric oxide synthesis [19, 20], may be related to CVD and T2D, as we have previously reported [21, 22].…”

Section: Discussionmentioning

confidence: 99%

Lysine pathway metabolites and the risk of type 2 diabetes and cardiovascular disease in the PREDIMED study: results from two case-cohort studies

Razquín

Ruiz‐Canela

Clish

et al. 2019

Cardiovasc Diabetol

View full text Add to dashboard Cite

BackgroundThe pandemic of cardiovascular disease (CVD) and type 2 diabetes (T2D) requires the identification of new predictor biomarkers. Biomarkers potentially modifiable with lifestyle changes deserve a special interest. Our aims were to analyze: (a) The associations of lysine, 2-aminoadipic acid (2-AAA) or pipecolic acid with the risk of T2D or CVD in the PREDIMED trial; (b) the effect of the dietary intervention on 1-year changes in these metabolites, and (c) whether the Mediterranean diet (MedDiet) interventions can modify the effects of these metabolites on CVD or T2D risk.MethodsTwo unstratified case-cohort studies nested within the PREDIMED trial were used. For CVD analyses, we selected 696 non-cases and 221 incident CVD cases; for T2D, we included 610 non-cases and 243 type 2 diabetes incident cases. Metabolites were quantified using liquid chromatography–tandem mass spectrometry, at baseline and after 1-year of intervention.ResultsIn weighted Cox regression models, we found that baseline lysine (HR+1 SD increase = 1.26; 95% CI 1.06–1.51) and 2-AAA (HR+1 SD increase = 1.28; 95% CI 1.05–1.55) were both associated with a higher risk of T2D, but not with CVD. A significant interaction (p = 0.032) between baseline lysine and T2D on the risk of CVD was observed: subjects with prevalent T2D and high levels of lysine exhibited the highest risk of CVD. The intervention with MedDiet did not have a significant effect on 1-year changes of the metabolites.ConclusionsOur results provide an independent prospective replication of the association of 2-AAA with future risk of T2D. We show an association of lysine with subsequent CVD risk, which is apparently diabetes-dependent. No evidence of effects of MedDiet intervention on lysine, 2-AAA or pipecolic acid changes was found.Trial registration ISRCTN35739639; registration date: 05/10/2005; recruitment start date 01/10/2003

show abstract

“…Wu [41] reported that the endogenous production of L-arginine is inadequate for the pregnant females. The significant increase in L-homoarginine concentrations during pregnancy may thus compensate for the insufficient endogenous production of L-arginine [42]. Unfortunately, the comprehensive physiological roles of the L-homoarginine during pregnancy still need to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Circulating Concentrations of Key Regulators of Nitric Oxide Production in Undernourished Sheep Carrying Single and Multiple Fetuses

Berlinguer

Porcu

Molle

et al. 2019

Animals

View full text Add to dashboard Cite

The aim of this study was to investigate the blood concentrations of L-arginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and L-homoarginine, which are regulators of nitric oxide (NO) synthesis, in single, twin, and triplet pregnancies in ewes undergoing either a dietary energy restriction or receiving 100% of their energy requirements. From day 24 to 100 of pregnancy, the ewes were fed ryegrass hay and two different iso-proteic concentrates fulfilling either 100% of ewes’ energy requirements (control group; n = 30, 14 singleton pregnancies, 12 twin pregnancies, and 4 triplet pregnancies) or only 45% (feed-restricted group; n = 29; 11 singleton pregnancies, 15 twin pregnancies, and 3 triplet pregnancies). Blood samples were collected monthly to measure, by capillary electrophoresis, the circulating concentrations of arginine, ADMA, homoarginine, SDMA, and of other amino acids not involved in NO synthesis to rule out possible direct effects of diet restriction on their concentrations. No differences between groups were observed in the circulating concentrations of most of the amino acids investigated. L-homoarginine increased markedly in both groups during pregnancy (p < 0.001). SDMA (p < 0.01), L-arginine, and ADMA concentrations were higher in feed-restricted ewes than in controls. The L-arginine/ADMA ratio, an indicator of NO production by NOS, decreased towards term without differences between groups. The ADMA/SDMA ratio, an index of the ADMA degrading enzyme activity, was higher in controls than in feed-restricted ewes (p < 0.001). Obtained results show that circulating concentrations of L-arginine, of its metabolites, and the ratio between NO synthesis boosters and inhibitors are altered in energy-restricted ewes, and that these alterations are more marked in ewes carrying multiple fetuses.

show abstract

Novel Biosynthesis, Metabolism and Physiological Functions of L-Homoarginine

Cited by 29 publications

References 0 publications

Hypoxic Adaptation of Mitochondrial Metabolism in Rat Cerebellum Decreases in Pregnancy

Hypoxic Adaptation of Mitochondrial Metabolism in Rat Cerebellum Decreases in Pregnancy

Lysine pathway metabolites and the risk of type 2 diabetes and cardiovascular disease in the PREDIMED study: results from two case-cohort studies

Circulating Concentrations of Key Regulators of Nitric Oxide Production in Undernourished Sheep Carrying Single and Multiple Fetuses

Contact Info

Product

Resources

About