Accelerated lysine metabolism conveys kidney protection in salt-sensitive hypertension. Nat Commun 2022 Jul 14;13(1):4099
Date
07/15/2022Pubmed ID
35835746Pubmed Central ID
PMC9283537DOI
10.1038/s41467-022-31670-0Scopus ID
2-s2.0-85134142317 (requires institutional sign-in at Scopus site) 18 CitationsAbstract
Hypertension and kidney disease have been repeatedly associated with genomic variants and alterations of lysine metabolism. Here, we combined stable isotope labeling with untargeted metabolomics to investigate lysine's metabolic fate in vivo. Dietary 13C6 labeled lysine was tracked to lysine metabolites across various organs. Globally, lysine reacts rapidly with molecules of the central carbon metabolism, but incorporates slowly into proteins and acylcarnitines. Lysine metabolism is accelerated in a rat model of hypertension and kidney damage, chiefly through N-alpha-mediated degradation. Lysine administration diminished development of hypertension and kidney injury. Protective mechanisms include diuresis, further acceleration of lysine conjugate formation, and inhibition of tubular albumin uptake. Lysine also conjugates with malonyl-CoA to form a novel metabolite Nε-malonyl-lysine to deplete malonyl-CoA from fatty acid synthesis. Through conjugate formation and excretion as fructoselysine, saccharopine, and Nε-acetyllysine, lysine lead to depletion of central carbon metabolites from the organism and kidney. Consistently, lysine administration to patients at risk for hypertension and kidney disease inhibited tubular albumin uptake, increased lysine conjugate formation, and reduced tricarboxylic acid (TCA) cycle metabolites, compared to kidney-healthy volunteers. In conclusion, lysine isotope tracing mapped an accelerated metabolism in hypertension, and lysine administration could protect kidneys in hypertensive kidney disease.
Author List
Rinschen MM, Palygin O, El-Meanawy A, Domingo-Almenara X, Palermo A, Dissanayake LV, Golosova D, Schafroth MA, Guijas C, Demir F, Jaegers J, Gliozzi ML, Xue J, Hoehne M, Benzing T, Kok BP, Saez E, Bleich M, Himmerkus N, Weisz OA, Cravatt BF, Krüger M, Benton HP, Siuzdak G, Staruschenko AAuthor
Ashraf El-Meanawy MD, PhD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AlbuminsAnimals
Carbon
Disease Models, Animal
Hypertension
Kidney
Lysine
Malonyl Coenzyme A
Rats