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 physiological ...

molecule, made up of the

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

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 Amine, α-amino group (which is in the protonated –NH3+ form under Physiological condition, biological conditions), a carboxylic ...

. It is highly concentrated in

muscle Muscle is a soft tissue, one of the four basic types of animal tissue. There are three types of muscle tissue in vertebrates: skeletal muscle, cardiac muscle, and smooth muscle. Muscle tissue gives skeletal muscles the ability to muscle contra ...

and

brain The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...

tissues. Carnosine was discovered by Russian chemist Vladimir Gulevich. 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 from the cytosol into mitochondria to be oxidized for f ...

, 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. Carnosine can chelate divalent metal ions. Carnosine is also considered a geroprotectant. Products containing carnosine are also used in topical preparations to reduce wrinkles on the skin. Carnosine may increase the Hayflick limit in human fibroblasts, it also appears to reduce the rate of telomere shortening. This could potentially promote the growth of certain cancers that thrive due to telomere preservation.

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 forms ...

. 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 * Lysis buffer, in cell biology * Metal ion buffer * Mineral redox buffer, in geology Technology and engineeri ...

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 shown to scavenge

reactive oxygen species In chemistry and biology, reactive oxygen species (ROS) are highly Reactivity (chemistry), reactive chemicals formed from diatomic oxygen (), water, and hydrogen peroxide. Some prominent ROS are hydroperoxide (H2O2), superoxide (O2−), hydroxyl ...

(ROS) as well as alpha-beta unsaturated

aldehydes In organic chemistry, an aldehyde () (lat. ''al''cohol ''dehyd''rogenatum, dehydrogenated alcohol) is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred ...

formed from peroxidation of cell membrane

fatty acids In chemistry, in particular 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, ...

during

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

. 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. : (1,2- dipolar compounds, such as ylides, are sometimes excluded from ...

, 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 Glycation, 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 dia ...

(substances that can be a factor in the development or worsening of many degenerative diseases, such as

diabetes Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or the cells of th ...

atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis, characterized by development of abnormalities called lesions in walls of arteries. This is a chronic inflammatory disease involving many different cell types and is driven by eleva ...

chronic kidney failure Chronic kidney disease (CKD) is a type of long-term kidney disease, defined by the sustained presence of abnormal kidney function and/or abnormal kidney structure. To meet criteria for CKD, the abnormalities must be present for at least three mo ...

, and

Alzheimer's disease Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...

), 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 typically with a spindle shape that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibrobla ...

, 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 (see #Sequences, Sequences). Telomeres are a widespread genetic feature most commonly found in eukaryotes. In ...

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

Other

Carnosine can

chelate Chelation () is a type of bonding of ions and their 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 l ...

divalent In chemistry, the valence (US spelling) or valency (British spelling) of an atom is a measure of its combining capacity with other atoms when it forms chemical compounds or molecules. Valence is generally understood to be the number of chemica ...

metal ions. It has been suggested that binding Ca²⁺ may displace protons, thereby providing a link between Ca²⁺ and H⁺ buffering. However, there is still controversy as to how much Ca²⁺ is bound to carnosine under physiological conditions.

References

{{Neuropeptides Dipeptides Anti-aging substances Dietary supplements