Blood levels of branched-chain amino acids and α-ketoacids in uremic patients given keto analogues of essential amino acids

Schauder, P.; Matthaei, D.; Henning, Hans; Scheler, F.; Langenbeck, U.

doi:10.1093/ajcn/33.7.1660

Cited by 27 publications

(8 citation statements)

References 13 publications

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“…Such a device could explain the improvement of the nitrogen balance and the reduction of urea nitrogen excretion following oxoisocaproate infusion in patients [32]. Further, such a mechanism also could explain the increased glutamate release by the liver in uivo during starvation [I 11, because starvation is known to increase considerably the serum concentrations of the oxoanalogues of leucine and isoleucine [33]. …”

Section: Discussionmentioning

confidence: 99%

Regulation of hepatic glutamate metabolism

Häussinger

Gerok

1984

European Journal of Biochemistry

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1. In isolated perfused rat liver, addition of the oxoanalogues of leucine, isoleucine, methionine and phenylalanine is followed by a rapid and reversible stimulation of glutamate release. This is not observed with the corresponding amino acids or 2-oxoisovalerate, 2-oxoglutarate or oxaloacetate.2. The increased glutamate release by the liver is accompanied by a decrease in the tissue contents of 2-oxoglutarate and glutamate by about 25 "i, and 50 %, respectively. 3.During the metabolism of glutamine, i.e. conditions with elevated tissue glutamate concentrations, 2-oxoacid-induced glutamate release is stimulated. In the presence of glutamine (5 mM), 2-oxoisocaproate, 2-0x0-4-methylvalerate and 2-0x0-4-methylthiobutyrate were found to be most effective and glutamate release by the liver increased linearly from about 80 nmol g-' min-to 600 nmol g-' min-~ ' at increasing 2-oxoacid concentrations up to 1 mM. When glutamate tissue levels were decreased by phenylephrine, stimulation of glutamate release by 2-oxoisocaproate was markedly diminished.4. 2-Oxoacid-stimulated glutamate release is independent of oxoacid metabolism, indicating that the effect is probably not explained by a 2-oxoacid/glutamate exchange across the liver plasma membrane. 2-Oxoacid-induced glutamate export predominantly occurs in a sodium-independent way.5. At low concentrations of 2-oxoisocaproate (below 0.2 mM), the increased glutamate release was accompanied by a slight inhibition of 14C02 production from added ['4C]glutamate, indicating a simultaneous glutamate uptake and release also under these conditions. 6. Stimulation of glutamate release by 2-oxoisocaproate is followed by a decreased rate of urea and glutamine synthesis from portal ammonia, as a consequence of an increased glutamate release.From the high intra/extracellular glutamate concentration gradient in liver, it was concluded that the plasma membrane of hepatocytes is virtually impermeable for glutamate [1,2]. However, it has been demonstrated that addition of [ l-'4C]glutamate to isolated perfused rat liver is followed by the production of 14C0, and other 14C-labeled compounds [3,4]. Studies with isolated rat liver plasma membrane vesicles showed the existence of a sodium-dependent transport system specific for aspartate and glutamate with a high substrate affinity, but a low transport capacity [5]. More recently, in cultured hepatocytes a high-affinity and a low-affinity component of this sodium-dependent glutamate transport system had been described besides a sodium-independent glutamate carrier [6].With respect to hepatocyte heterogeneity in ammonia and glutamine metabolism 17 -91 portal glutamate is predominantly taken up by the perivenous glutamine-synthetasecontaining hepatocytes and an about 20-fold higher glutamate transport capacity has been calculated for these hepatocytes compared to others [4]. These studies also showed that glutamate is simultaneously taken up and released by perfused Llcdicated to Prof. Dr Karl Decker on the occasion of his 60th birthday.Enzymes. 2...

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Section: Discussionmentioning

confidence: 99%

Regulation of hepatic glutamate metabolism

Häussinger

Gerok

1984

European Journal of Biochemistry

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“…Most studies of amino acid patterns in CRF reported decreased BCAA and BCKA levels in the blood plasma [ 59 – 61 ] and reduced concentrations of valine in muscles [ 61 , 62 ]. The derangements are caused by the action of multiple factors, notably acidosis and glucocorticoids.…”

Section: Disorders With Decreased Bcaa Levelsmentioning

confidence: 99%

Branched-chain amino acids in health and disease: metabolism, alterations in blood plasma, and as supplements

2018

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Branched-chain amino acids (BCAAs; valine, leucine, and isoleucine) are essential amino acids with protein anabolic properties, which have been studied in a number of muscle wasting disorders for more than 50 years. However, until today, there is no consensus regarding their therapeutic effectiveness.In the article is demonstrated that the crucial roles in BCAA metabolism play: (i) skeletal muscle as the initial site of BCAA catabolism accompanied with the release of alanine and glutamine to the blood; (ii) activity of branched-chain keto acid dehydrogenase (BCKD); and (iii) amination of branched-chain keto acids (BCKAs) to BCAAs. Enhanced consumption of BCAA for ammonia detoxification to glutamine in muscles is the cause of decreased BCAA levels in liver cirrhosis and urea cycle disorders. Increased BCKD activity is responsible for enhanced oxidation of BCAA in chronic renal failure, trauma, burn, sepsis, cancer, phenylbutyrate-treated subjects, and during exercise. Decreased BCKD activity is the main cause of increased BCAA levels and BCKAs in maple syrup urine disease, and plays a role in increased BCAA levels in diabetes type 2 and obesity. Increased BCAA concentrations during brief starvation and type 1 diabetes are explained by amination of BCKAs in visceral tissues and decreased uptake of BCAA by muscles.The studies indicate beneficial effects of BCAAs and BCKAs in therapy of chronic renal failure. New therapeutic strategies should be developed to enhance effectiveness and avoid adverse effects of BCAA on ammonia production in subjects with liver cirrhosis and urea cycle disorders. Further studies are needed to elucidate the effects of BCAA supplementation in burn, trauma, sepsis, cancer and exercise. Whether increased BCAA levels only markers are or also contribute to insulin resistance should be known before the decision is taken regarding their suitability in obese subjects and patients with type 2 diabetes.It is concluded that alterations in BCAA metabolism have been found common in a number of disease states and careful studies are needed to elucidate their therapeutic effectiveness in most indications.

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“…3d) as compared to the healthy and non-COVID-19 groups (p-value = 8E-06 coefficient -0.4 for leucine in Severe COVID-19 vs. healthy group). BCAAs play a critical role in protein anabolism 29 , lowered BCAA levels are often observed in various conditions, including liver cirrhosis 30 , urea cycle disorders 31 , chronic renal failure 32,33 , and impaired renal function 34 . Thus, our finding is congruent with the impaired renal function observed in severe COVID-19 cases 35 .…”

Section: Multi-organ Dysfunctionmentioning

confidence: 99%

Metabolite, Protein, And Tissue Dysfunction Associated With COVID-19 Disease Severity

Rahnavard

Mann

Giri

et al. 2021

Preprint

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Proteins are direct products of the genome and metabolites are functional products of interactions between the host and other factors such as environment, disease state, clinical information, etc. Omics data, including proteins and metabolites, are useful in characterizing biological processes underlying COVID-19 along with patient data and clinical information, yet few methods are available to effectively analyze such diverse and unstructured data. Using an integrated approach that combines proteomics and metabolomics data, we investigated the changes in metabolites and proteins in relation to patient characteristics (e.g., age, gender, and health outcome) and clinical information (e.g., metabolic panel and complete blood count test results). We found significant enrichment of biological indicators of lung, liver, and gastrointestinal dysfunction associated with disease severity using metabolite and protein profiles. Our analyses specifically identified enriched proteins that play a critical role in responses to injury or infection within these anatomical sites, but may contribute to excessive systemic inflammation within the context of COVID-19. Furthermore, we have used this information in conjunction with machine learning algorithms to predict the health status of patients presenting symptoms of COVID-19. This work provides a roadmap for understanding the biochemical pathways and molecular mechanisms that drive disease severity, progression, and treatment of COVID-19.

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Blood levels of branched-chain amino acids and α-ketoacids in uremic patients given keto analogues of essential amino acids

Cited by 27 publications

References 13 publications

Regulation of hepatic glutamate metabolism

Regulation of hepatic glutamate metabolism

Branched-chain amino acids in health and disease: metabolism, alterations in blood plasma, and as supplements

Metabolite, Protein, And Tissue Dysfunction Associated With COVID-19 Disease Severity

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