Origin and characteristics of an unusual pyridine nucleotide accumulating in erythrocytes: positive correlation with degree of renal failure

Carrey, Elizabeth A.; Smolenski, Ryszard T.; Edbury, S. M.; Laurence, Arian; Duley, John A.; Zhu, Li‐Min; Goldsmith, David; Simmonds, H. Anne

doi:10.1016/s0009-8981(03)00294-8

Cited by 30 publications

(43 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These data indicate that the healthy human erythrocyte concentration of 4PYTP is significant, corresponding to ϳ2% of the ATP level. Massive accumulation of 4PYTP was observed in patients with renal failure, up to 10% of ATP on average or up to 30% in advanced chronic renal failure, which is consistent with our previous suggestions (7,8). Fig.…”

Section: Formation Of 4pytp In the Erythrocytes And Itssupporting

confidence: 91%

“…These results together with data from our earlier study (7,8) provide evidence for the pathway by which 4PYTP is formed in the erythrocytes. Because specific inhibitor totally blocked this process, nucleoside phosphorylation mediated by adenosine kinase is the most likely step leading to incorporation of 4PYR into the nucleotide pool.…”

Section: Formation Of 4pytp In the Erythrocytes And Itssupporting

confidence: 79%

“…However, the exact source and pathway leading to the formation of 4PYR in plasma is less certain. We suggested earlier that the activity of aldehyde oxidase is essential for generation of the 4PYR, as no 4PYTP accumulation was observed in an erythrocyte extract of a patient with molybdenum cofactor deficiency who developed chronic renal failure (7,8). Because aldehyde oxidase is not present in the erythrocytes (liver is the major site of its expression in humans (30)), formation of erythrocyte 4PYTP may depend on the provision of 4PYR into the circulation by the other organs, such as the liver.…”

Section: Formation Of 4pytp In the Erythrocytes And Itsmentioning

confidence: 97%

“…Therefore, it was very surprising for us to note an unknown nucleoside triphosphate that was present at high levels in the erythrocytes of patients with renal failure but also at low concentrations in the erythrocytes of healthy subjects (7,8). A correlation between concentrations of this unknown nucleotide in erythrocytes and the plasma concentration of a nicotinamide catabolite N-methyl-2-pyridone-5-carboxamide (Met2PY) 2 suggested that both compounds could be related (7,8). However, further comparison of chemical properties indicated that this is not the case.…”

Section: H Nuclear Magnetic Resonance and Infrared Spectroscopy As 4-mentioning

confidence: 99%

See 3 more Smart Citations

A Novel Nucleotide Found in Human Erythrocytes, 4-Pyridone-3-carboxamide-1-β-d-ribonucleoside Triphosphate

Słomińska

Carrey

Foks

et al. 2006

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

We report the identification of a hitherto unknown nucleotide that is present in micromolar concentrations in the erythrocytes of healthy subjects and accumulates at levels comparable with the ATP concentration in erythrocytes of patients with chronic renal failure. The unknown nucleotide was isolated and identified by liquid chromatography with UV and tandem mass detection, . We suggest that 4PYTP formation in the erythrocytes is a hitherto unknown process aimed at sequestering potentially toxic 4PYR in a form that could be safely transported and subsequently released and excreted during passage of erythrocytes through the kidney.

show abstract

Section: Formation Of 4pytp In the Erythrocytes And Itssupporting

confidence: 91%

Section: Formation Of 4pytp In the Erythrocytes And Itssupporting

confidence: 79%

Section: Formation Of 4pytp In the Erythrocytes And Itsmentioning

confidence: 97%

Section: H Nuclear Magnetic Resonance and Infrared Spectroscopy As 4-mentioning

confidence: 99%

See 2 more Smart Citations

A Novel Nucleotide Found in Human Erythrocytes, 4-Pyridone-3-carboxamide-1-β-d-ribonucleoside Triphosphate

Słomińska

Carrey

Foks

et al. 2006

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…N-methyl-2-pyridone-5-carboxamide (Met2PY) and N-methyl-4-pyridone-3-carboxamide (Met4PY) are the end products of nicotinamide-adenine dinucleotide (NAD) degradation (Carrey et al, 2003). Rutkowski et al identified Met2PY and Met4PY as uremic toxins (Slominska et al, 2002;Rutkowski et al, 2003Rutkowski et al, , 2008Rutkowski et al, , 2010.…”

Section: Nicotinamide Metabolitesmentioning

confidence: 99%

Update of uremic toxin research by mass spectrometry

Niwa

2011

Mass Spectrometry Reviews

View full text Add to dashboard Cite

Mass spectrometry (MS) has been successfully applied for the identification and quantification of uremic toxins and uremia-associated modified proteins. This review focuses on the recent progress in the MS analysis of uremic toxins. Uremic toxins include low-molecular weight solutes, protein-bound low-molecular weight solutes, and middle molecules (peptides and proteins). Based on MS analysis of these uremic toxins, the pathogenesis of the uremic symptoms will be elucidated to prevent and manage the symptoms. Notably, protein-bound uremic toxins such as indoxyl sulfate, p-cresyl sulfate, and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid have emerged as important targets of therapeutic removal. Hemodialysis even with a high-flux membrane cannot efficiently remove the protein-bound uremic toxins because of their high albumin-binding property. The accumulation of these protein-bound uremic toxins in the blood of dialysis patients might play an important role in the development of uremic complications such as cardiovascular disease. Indoxyl sulfate is the most promising protein-bound uremic toxin as a biomarker of progress in chronic kidney disease. Novel dialysis techniques or membranes should be developed to efficiently remove these protein-bound uremic toxins for the prevention and management of uremic complications.

show abstract

Nicotinamide Metabolites

Rutkowski

2012

Uremic Toxins

View full text Add to dashboard Cite

Origin and characteristics of an unusual pyridine nucleotide accumulating in erythrocytes: positive correlation with degree of renal failure

Cited by 30 publications

References 23 publications

A Novel Nucleotide Found in Human Erythrocytes, 4-Pyridone-3-carboxamide-1-β-d-ribonucleoside Triphosphate

A Novel Nucleotide Found in Human Erythrocytes, 4-Pyridone-3-carboxamide-1-β-d-ribonucleoside Triphosphate

Update of uremic toxin research by mass spectrometry

Nicotinamide Metabolites

Contact Info

Product

Resources

About