Carnosine (''beta''-alanyl-L-histidine) is a

dipeptide A dipeptide is an organic compound derived from two amino acids. The constituent amino acids can be the same or different. When different, two isomers of the dipeptide are possible, depending on the sequence. Several dipeptides are physiologicall ...

molecule, made up of the

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

s beta-alanine and

histidine Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated –NH3+ form under biological conditions), a carboxylic acid group (which is in the de ...

. It is highly concentrated in

muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...

and

brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...

tissues. Carnosine was discovered by Russian chemist

Vladimir Gulevich Vladimir Sergeevich Gulevich (russian: Владимир Сергеевич Гулевич; 18 November 1867 – 6 September 1933) was a Russian and Soviet biochemist who first isolated carnitine from mammalian muscle. Biography Gulevich graduated ...

. Carnosine is naturally produced by the body in the liver from beta-alanine and

. Like

carnitine Carnitine is a quaternary ammonium compound involved in metabolism in most mammals, plants, and some bacteria. In support of energy metabolism, carnitine transports long-chain fatty acids into mitochondria to be oxidized for energy production, an ...

, carnosine is composed of the root word ''carn'', meaning "flesh", alluding to its prevalence in meat. There are no plant-based sources of carnosine. Carnosine is readily available as a synthetic nutritional supplement.

Biosynthesis

Carnosine is synthesized within the body from beta-alanine and

. Beta-alanine is a product of pyrimidine catabolism and histidine is an

essential amino acid An essential amino acid, or indispensable amino acid, is an amino acid that cannot be synthesized from scratch by the organism fast enough to supply its demand, and must therefore come from the diet. Of the 21 amino acids common to all life form ...

. Since beta-alanine is the limiting substrate, supplementing just beta-alanine effectively increases the intramuscular concentration of carnosine.

Physiological effects

pH buffer

Carnosine has a pK_a value of 6.83, making it a good

buffer Buffer may refer to: Science * Buffer gas, an inert or nonflammable gas * Buffer solution, a solution used to prevent changes in pH * Buffering agent, the weak acid or base in a buffer solution * Lysis buffer, in cell biology * Metal ion buffer * ...

for the pH range of animal muscles. Since beta-alanine is not incorporated into proteins, carnosine can be stored at relatively high concentrations (millimolar). Occurring at 17–25 mmol/kg (dry muscle), carnosine (β-alanyl-L-histidine) is an important intramuscular buffer, constituting 10-20% of the total buffering capacity in type I and II muscle fibres.

Anti-oxidant

Carnosine has been proven to scavenge

reactive oxygen species In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of molecular oxygen () p ...

(ROS) as well as alpha-beta unsaturated

aldehydes In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl group ...

formed from peroxidation of cell membrane

fatty acids In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, f ...

during

oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily Detoxification, detoxify the reactive intermediates or to repair the resulting damage. Disturbances ...

. It also buffers pH in muscle cells, and acts as a neurotransmitter in the brain. It is also a

zwitterion In chemistry, a zwitterion ( ; ), also called an inner salt or dipolar ion, is a molecule that contains an equal number of positively- and negatively-charged functional groups. : With amino acids, for example, in solution a chemical equilibrium wil ...

, a neutral molecule with a positive and negative end.

Antiglycating

Carnosine acts as an antiglycating agent, reducing the rate of formation of

advanced glycation end-products Advanced glycation end products (AGEs) are proteins or lipids that become glycated as a result of exposure to sugars. They are a bio-marker implicated in aging and the development, or worsening, of many degenerative diseases, such as diabetes, at ...

(substances that can be a factor in the development or worsening of many

degenerative diseases Degenerative disease is the result of a continuous process based on degenerative cell changes, affecting biological tissue, tissues or Organ (anatomy), organs, which will increasingly deteriorate over time. In neurodegenerative diseases, cells of ...

, such as

diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...

atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheroma, atheromatous plaque. At onset there are usu ...

chronic kidney failure Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vom ...

, and

Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...

), and ultimately reducing development of atherosclerotic plaque build-up.

Geroprotective

Carnosine is considered as a geroprotector. Carnosine can increase the Hayflick limit in human

fibroblasts A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells o ...

, as well as appearing to reduce the

telomere A telomere (; ) is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes. Although there are different architectures, telomeres, in a broad sense, are a widespread genetic feature mos ...

shortening rate. Carnosine may also slow aging through its anti-glycating properties (chronic glycolysis is speculated to accelerate aging).

Other

Carnosine can

chelate Chelation is a type of bonding of ions and molecules to metal ions. It involves the formation or presence of two or more separate coordinate bonds between a polydentate (multiple bonded) ligand and a single central metal atom. These ligands are ...

divalent In chemistry, the valence (US spelling) or valency (British spelling) of an element is the measure of its combining capacity with other atoms when it forms chemical compounds or molecules. Description The combining capacity, or affinity of an ...

metal ions. Carnosine administration has been shown to have cardioprotective properties, protecting against ischaemia-reperfusion injury, and doxorubicin-induced cardiomyopathy. Carnosine demonstrated neuroprotective effects in multiple animal studies. Research has demonstrated a positive association between muscle tissue carnosine concentration and exercise performance. β-Alanine supplementation is thought to increase exercise performance by promoting carnosine production in muscle. Exercise has conversely been found to increase muscle carnosine concentrations, and muscle carnosine content is higher in athletes engaging in anaerobic exercise. Carnosine appears to protect in experimental ischemic stroke by influencing a number of mechanisms that are activated during stroke. It is a potent pH buffer and has anti-matrix metalloproteinase activity, antioxidant and antiexcitotoxic properties and protects the blood brain barrier.

References

{{Neuropeptides Dipeptides Anti-aging substances Dietary supplements