ArticleThe Journal of biological chemistry2013
Role of aldose reductase in the metabolism and detoxification of carnosine-acrolein conjugates.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 95 citations in OpenAlex.
- Effect of Carnosine or β-Alanine Supplementation on Markers of Glycemic Control and Insulin Resistance in Humans and Animals: A Systematic Review and Meta-analysis.Advances in nutrition (Bethesda, Md.) · 2021Pooled it
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- Trial
- Carnosinylation of Cardiac Antigens Attenuates Immunogenic Responses and Improves Function in Failing Hearts.Journal of the American Heart Association · 2026Article
- Structural and Metabolic Remodeling of Skeletal Muscle in Heart Failure with Reduced Ejection Fraction: A Review: Beyond the Failing Heart.International journal of molecular sciences · 2026Review
- The Carnosine-HNE Michael Adduct as a Redox-Active Species Associated with Nrf2-Dependent Antioxidant and Anti-Inflammatory Responses.Antioxidants (Basel, Switzerland) · 2026Article
- Preclinical evidence and therapeutic perspectives on carnosine for the treatment of neurodegenerative disorders.AIMS neuroscience · 2025Review
- Metabolic pathways for removing reactive aldehydes are diminished in the skeletal muscle during heart failure.Skeletal muscle · 2024Article
- Quantitative Analysis of Glutathione and Carnosine Adducts with 4-Hydroxy-2-nonenal in Muscle in a hSOD1Chemical research in toxicology · 2024Article
- Exploring protein relative relations in skeletal muscle proteomic analysis for insights into insulin resistance and type 2 diabetes.Scientific reports · 2024Article
- Reactive Carbonyl Species Scavenger: Epigallocatechin-3-Gallate.Foods (Basel, Switzerland) · 2024Review
- Metabolic Pathways for Removing Reactive Aldehydes are Diminished in Atrophic Muscle During Heart Failure.Research square · 2023Article
- Skeletal muscle analysis of cancer patients reveals a potential role for carnosine in muscle wasting.Journal of cachexia, sarcopenia and muscle · 2023Article
- Carnosine increases insulin-stimulated glucose uptake and reduces methylglyoxal-modified proteins in type-2 diabetic human skeletal muscle cells.Amino acids · 2023Article
- Iron scavenging and suppression of collagen cross-linking underlie antifibrotic effects of carnosine in the heart with obesity.Frontiers in pharmacology · 2023Article
- Physiological Roles of Carnosine in Myocardial Function and Health.Advances in nutrition (Bethesda, Md.) · 2022Review
- Integrated Multilayer Omics Reveals the Genomic, Proteomic, and Metabolic Influences of Histidyl Dipeptides on the Heart.Journal of the American Heart Association · 2022Article
- Absence of endogenous carnosine synthesis does not increase protein carbonylation and advanced lipoxidation end products in brain, kidney or muscle.Amino acids · 2022Article
- Synergistic Effect of L-Carnosine and Hyaluronic Acid in Their Covalent Conjugates on the Antioxidant Abilities and the Mutual Defense against Enzymatic Degradation.Antioxidants (Basel, Switzerland) · 2022Article
- Carnosine quenches the reactive carbonyl acrolein in the central nervous system and attenuates autoimmune neuroinflammation.Journal of neuroinflammation · 2021Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Oxidation of unsaturated lipids generates reactive aldehydes that accumulate in tissues during inflammation, ischemia, or aging. These aldehydes form covalent adducts with histidine-containing dipeptides such as carnosine and anserine, which are present in high concentration in skeletal muscle, heart, and brain. The metabolic pathways involved in the detoxification and elimination of these conjugates are, however, poorly defined, and their significance in regulating oxidative stress is unclear. Here we report that conjugates of carnosine with aldehydes such as acrolein are produced during normal metabolism and excreted in the urine of mice and adult human non-smokers as carnosine-propanols. Our studies show that the reduction of carnosine-propanals is catalyzed by the enzyme aldose reductase (AR). Carnosine-propanals were converted to carnosine-propanols in the lysates of heart, skeletal muscle, and brain tissue from wild-type (WT) but not AR-null mice. In comparison with WT mice, the urinary excretion of carnosine-propanols was decreased in AR-null mice. Carnosine-propanals formed covalent adducts with nucleophilic amino acids leading to the generation of carnosinylated proteins. Deletion of AR increased the abundance of proteins bound to carnosine in skeletal muscle, brain, and heart of aged mice and promoted the accumulation of carnosinylated proteins in hearts subjected to global ischemia ex vivo. Perfusion with carnosine promoted post-ischemic functional recovery in WT but not in AR-null mouse hearts. Collectively, these findings reveal a previously unknown metabolic pathway for the removal of carnosine-propanal conjugates and suggest a new role of AR as a critical regulator of protein carnosinylation and carnosine-mediated tissue protection.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.