Amino Acids in the Blood and Urine of Human Subjects Ingesting Different Amounts of the Same Proteins

Steele, Betty F.; Reynolds, May S.; Baumann, C. A.

doi:10.1093/jn/40.1.145

Cited by 46 publications

(5 citation statements)

References 18 publications

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“…Urine concentrations of branch-chain amino acids may depend on protein intake. We do not have data on diet, but secretion for most amino acids is not strongly influenced by protein intake in healthy individuals [ 23 ]. However, high protein intake in prevalent CKD may further kidney function decline [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Urinary metabolite profiling and risk of progression of diabetic nephropathy in 2670 individuals with type 1 diabetes

Mutter

Valo

Aittomäki³

et al. 2021

Diabetologia

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Aims/hypothesis This prospective, observational study examines associations between 51 urinary metabolites and risk of progression of diabetic nephropathy in individuals with type 1 diabetes by employing an automated NMR metabolomics technique suitable for large-scale urine sample collections. Methods We collected 24-h urine samples for 2670 individuals with type 1 diabetes from the Finnish Diabetic Nephropathy study and measured metabolite concentrations by NMR. Individuals were followed up for 9.0 ± 5.0 years until their first sign of progression of diabetic nephropathy, end-stage kidney disease or study end. Cox regressions were performed on the entire study population (overall progression), on 1999 individuals with normoalbuminuria and 347 individuals with macroalbuminuria at baseline. Results Seven urinary metabolites were associated with overall progression after adjustment for baseline albuminuria and chronic kidney disease stage (p < 8 × 10−4): leucine (HR 1.47 [95% CI 1.30, 1.66] per 1-SD creatinine-scaled metabolite concentration), valine (1.38 [1.22, 1.56]), isoleucine (1.33 [1.18, 1.50]), pseudouridine (1.25 [1.11, 1.42]), threonine (1.27 [1.11, 1.46]) and citrate (0.84 [0.75, 0.93]). 2-Hydroxyisobutyrate was associated with overall progression (1.30 [1.16, 1.45]) and also progression from normoalbuminuria (1.56 [1.25, 1.95]). Six amino acids and pyroglutamate were associated with progression from macroalbuminuria. Conclusions/interpretation Branched-chain amino acids and other urinary metabolites were associated with the progression of diabetic nephropathy on top of baseline albuminuria and chronic kidney disease. We found differences in associations for overall progression and progression from normo- and macroalbuminuria. These novel discoveries illustrate the utility of analysing urinary metabolites in entire population cohorts. Graphical abstract

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Section: Discussionmentioning

confidence: 99%

Urinary metabolite profiling and risk of progression of diabetic nephropathy in 2670 individuals with type 1 diabetes

Mutter

Valo

Aittomäki³

et al. 2021

Diabetologia

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“…Serum aspartate content, like other amino acidic contents, is highly variable, being dependent on age and nutrition . For instance, many of the children in malaria-endemic regions possess extremely low, even undetectable, levels of plasma amino acids. , Studies that measured specific levels of aspartate in serum have reported values that disagree by more than 10 orders of magnitude. ,− However, the consensus is that aspartate is one the least common (the least common according to ref ) amino acids available within human serum. Moreover, although aspartate is available in hemoglobin, which is used as a source of amino acids (except isoleucine) during the blood stage, the PIA experiments on AspAT and MDH enzymes suggested the insufficiency of this source to support rapid proliferation of the parasite .…”

Section: Discussionmentioning

confidence: 99%

Molecular Target Validation of Aspartate Transcarbamoylase from Plasmodium falciparum by Torin 2

et al. 2020

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Malaria is a tropical disease that kills about half a million people around the world annually. Enzymatic reactions within pyrimidine biosynthesis have been proven to be essential for Plasmodium proliferation. Here we report on the essentiality of the second enzymatic step of the pyrimidine biosynthesis pathway, catalyzed by aspartate transcarbamoylase (ATC). Crystallization experiments using a double mutant ofPlasmodium falciparum ATC (PfATC) revealed the importance of the mutated residues for enzyme catalysis. Subsequently, this mutant was employed in protein interference assays (PIAs), which resulted in inhibition of parasite proliferation when parasites transfected with the double mutant were cultivated in medium lacking an excess of nutrients, including aspartate. Addition of 5 or 10 mg/L of aspartate to the minimal medium restored the parasites' normal growth rate. In vitro and whole-cell assays in the presence of the compound Torin 2 showed inhibition of specific activity and parasite growth, respectively. In silico analyses revealed the potential binding mode of Torin 2 to PfATC. Furthermore, a transgenic ATCoverexpressing cell line exhibited a 10-fold increased tolerance to Torin 2 compared with control cultures. Taken together, our results confirm the antimalarial activity of Torin 2, suggesting PfATC as a target of this drug and a promising target for the development of novel antimalarials.

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“…About one-tenth of the population excretes P-aminoisobutyric acid in amounts as high as 200 mg in 24 hours (Crumpler, Dent, Harris & Westall 1951 (Evered 1956). In the literature there have been described unsuccessful attempts to correlate the excretion of several amino acids with body weight, or with the elimination of creatinine, ammonia or uric acid (Steele et al 1950; Woodson et al 1948). Only the urinary threonine and leucine, but not lysine, were related to body weight (Thompson & Kirby acids is generally high.…”

Section: Earlier Relevant Investigationsmentioning

confidence: 99%

Urinary and Blood Amino Acids in Rheumatoid Arthritis

Kulonen¹,

Kulonen²

1960

Scand J Clin Lab Invest

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Amino Acids in the Blood and Urine of Human Subjects Ingesting Different Amounts of the Same Proteins

Cited by 46 publications

References 18 publications

Urinary metabolite profiling and risk of progression of diabetic nephropathy in 2670 individuals with type 1 diabetes

Urinary metabolite profiling and risk of progression of diabetic nephropathy in 2670 individuals with type 1 diabetes

Molecular Target Validation of Aspartate Transcarbamoylase from Plasmodium falciparum by Torin 2

Urinary and Blood Amino Acids in Rheumatoid Arthritis

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