Carnosine Metabolism and Its Physiological Implications

Carnosine is an endogenous dipeptide synthesised primarily in skeletal muscle and the central nervous system by carnosine synthase and degraded by carnosinases. Its biochemical activities include pH buffering, metal-ion chelation and scavenging of reactive oxygen and nitrogen species. These properties underpin protective roles in muscle fatigue resistance, neurotransmission and cellular defence against oxidative damage. Beyond these classical functions, emerging evidence links carnosine metabolism to modulation of glucose homeostasis, attenuation of inflammatory signalling and preservation of tissue integrity in ageing and chronic disease. Alterations in carnosine turnover have been implicated in neurodegenerative disorders, metabolic syndrome and diabetic complications, suggesting that fine-tuning of synthesis, hydrolysis and conjugation pathways may offer novel avenues for therapeutic intervention.

Research from Nature Portfolio

In a mammalian model of type 2 diabetes, long-term supplementation with carnosine improved glycaemic control, raised circulating insulin and C-peptide levels, and reduced albuminuria and renal hypertrophy. Histological analyses revealed restoration of glomerular ultrastructure and reduced mesangial expansion, accompanied by formation of protective carnosine–acrolein adducts. This work demonstrates that augmenting endogenous dipeptide pools can both ameliorate systemic metabolic dysregulation and preserve kidney function, highlighting carnosine as a candidate for preventing or treating diabetic nephropathy.

Carnosine Metabolism and Its Physiological Implications publication trend

The graph below shows the total number of articles in carnosine metabolism and its physiological implications across all publications each year (not limited to Nature Index journals).

Technical terms

Carnosine: Endogenous dipeptide composed of β-alanine and L-histidine, abundant in muscle and brain, with antioxidant, pH-buffering and metal-chelating functions.

Carnosinase: Enzyme that hydrolyses carnosine into constituent amino acids, regulating its bioavailability and physiological effects.

Oxidative stress: Cellular damage caused by imbalance between reactive oxygen species generation and antioxidant defence mechanisms.

Diabetic nephropathy: Progressive kidney damage in diabetes characterised by proteinuria, glomerular sclerosis and declining renal function.

Nrf2: Transcription factor that, upon activation, induces expression of a network of genes encoding antioxidant and cytoprotective proteins.

References

1. Molecular Identification of Carnosine Synthase as ATP-grasp Domain-containing Protein 1 (ATPGD1)*. Journal of Biological Chemistry (2010).
2. Carnosinases, Their Substrates and Diseases. Molecules (2014).
3. Important roles of dietary taurine, creatine, carnosine, anserine and 4-hydroxyproline in human nutrition and health. Amino Acids (2020).
4. Carnosine Attenuates the Development of both Type 2 Diabetes and Diabetic Nephropathy in BTBR ob/ob Mice. Scientific Reports (2017).
5. Human carnosinases: A brief history, medicinal relevance, and in silico analyses. Drug Discovery Today (2023).
6. Carnosine supplementation improves cognitive outcomes in younger participants of the NEAT trial. Neurotherapeutics (2025).
7. Copper(II) Complexes with Carnosine Conjugates of Hyaluronic Acids at Different Dipeptide Loading Percentages Behave as Multiple SOD Mimics and Stimulate Nrf2 Translocation and Antioxidant Response in In Vitro Inflammatory Model. Antioxidants (2023).