Beta-alanyl-L-histidine

Written by Ypera Lifesciences™. Posted in Science Blog.

Beta-alanyl-L-histidine (Carnosine) is one of the active QoL Enhancer ™ ingredients in the proprietary Molecular Action Blend ™ of Ypera ®.

Introduction

Carnosine (β-Alanyl-L-histidine or beta-alanyl-L-histidine) was discovered in 1900 as an abundant non-protein nitrogen-containing compound of meat. The dipeptide is not only found in skeletal muscle, but also other excitable tissues. Most animals, except humans, also possess a methylated variant of carnosine, either anserine or ophidine/balenine collectively called the histidine-containing dipeptides. This review aims to decipher the physiological roles of carnosine, based on its biochemical properties. The latter include pH-buffering, metal ion chelation, and antioxidant capacity as well as the ability to protect against the formation of advanced glycation and lipoxidation end-products. 

For these reasons, the therapeutic potential of carnosine supplementation has been tested in numerous diseases in which ischemic or oxidative stress is involved. For several pathologies, such as diabetes and its complications, ocular disease, aging, and neurological disorders, promising preclinical and clinical results have been obtained. Also, the pathophysiological relevance of serum carnosinase, the enzyme actively degrading carnosine into L-histidine and -alanine is discussed. The carnosine system has evolved as a pluripotent solution to many homeostatic challenges. (105)

Specification

Nomenclature

IUPAC name: (2S)-2-[(3-Amino-1-oxopropyl)amino]-3-(3H-imidazol-4-yl)propanoic acid

Chemical name: β-Alanyl-L-histidine or beta-alanyl-L-histidine

CAS Registry number: 305-84-0

Structure

Structural formula

Beta-alanyl-L-histidine (Carnosine) is one of the active ingredients of Ypera ®

Molecular formula: C9H14N4O3

Molecular mass: 226.24 g·mol−1

General Properties

Appearance: Crystalline solid

Melting point: 253 °C (487 °F; 526 K) (decomposition)

Safety

The LD50 in oral intake of mice is = >14930 mg/kg. This is a normally unreachable dose for humans consuming carnosine containing supplements. Therefore, the supplementation is generally considered as uncritical.

L-Carnosine is not listed as a carcinogen by ACGIH, IARC, NTP, or CA Prop 65.

Antioxidant Activity

The antioxidant activity of carnosine was initially studied by Boldyrev et al. since the 1980s (106 – 110). Later on, several studies were reported, showing a direct and indirect antioxidant activity of carnosine, as demonstrated in several in vitro studies (see below). The antioxidant activity of carnosine is mediated by different mechanisms involving metal ion chelation and scavenging reactive oxygen species (ROS) and peroxyl radicals.

At physiological concentrations, carnosine was found to directly react with superoxide anion like superoxide dismutase (SOD), and the constant for the interaction of carnosine with O2· was calculated to be 105 M 1·s 1 and not significantly different in respect to that of ascorbic acid and -tocopherol (111). The mechanism of interaction of carnosine with superoxide radicals was studied by Pavlov et al. (112) in water solutions and is based on the ability of carnosine to form a charge-transfer complex with the superoxide radical which changes the reactivity of O2·. Carnosine is also an effective quencher of other ROS such as hydroxyl radicals (·OH). In particular, evidence was provided through pulse- radiolysis (113), indicating that carnosine is an adequate scavenger of OH radicals.

Inhibiting Protein Carbonylisation and Glycolysation

Several in vitro and in vivo studies have reported the ability of carnosine and related peptides to prevent the formation of advanced lipoxidation end-products (ALEs) and advanced glycoxidation end- products (AGEs). These compounds are both involved in the aging process as well as in the onset and propagation of several oxidative-based diseases such as diabetes, atherosclerosis, and Alzheimer’s disease.

Hipkiss first reported a series of papers showing the ability of carnosine to inhibit AGEs and ALEs formation induced by different precursors, including reducing sugars such as glucose (114), deoxyribose, ribose, fructose(115), and reactive carbonyls such as malondialdehyde (116, 117), glyoxal, methylglyoxal (118), acetaldehyde, and formaldehyde (119).

Carnosin Content in the Muscle

An essential aspect of the physiological role of carnosine in skeletal muscle is related to contractile function in general and more specifically to excitation-contraction coupling (calcium handling) as well as to the protection against exercise-induced acidosis (pH buffering). 

Thus possessing high muscle carnosine content may be advantageous for high-intensity exercise capacity. Below we will discuss the determinants of muscle carnosine content in humans, its implications for exercise capacity, as well as the nutritional strategies that influence muscle carnosine content.

There is a considerable variation in muscle carnosine con- tent among humans, as three- to fourfold differences have been demonstrated between the lowest ( 10 mmol/kg dry wt) and highest ( 40 mmol/kg dry wt) reported levels in humans (120) (121, 122) (123). Despite the sizeable interindividual variation, the intraindividual difference is somewhat limited. Re- peated measurements of muscle carnosine over time in the same person displays only small fluctuations (124), and very high correlations have been found for muscle carnosine content within monozygotic twin pairs (125).

It has been suggested that exercise training can also alter muscle carnosine content. However, most short-term training intervention studies seem to agree that a few weeks of training will not stimulate carnosine accumulation in muscle (126–129). 

It remains to be established whether long-term (months to years) training intervention can modulate muscle carnosine content, especially when this chronic exercise intervention is possibly accompanied by a shift in fiber type composition (130).

Carnosine in Sports Nutrition

The above-described carnosine supplementation-induced muscle carnosine loading strategy is beneficial for certain types of exercise performance. In 2012, Hill et al. (131) reported that the capacity to cycle at 110% of maximal power (Wmax) was improved by 13 and 16% following, respectively, 4 and 10 wk of chronic carnosine supplementation in healthy untrained volunteers. 

Later studies confirmed that ergogenic effects could also be obtained in well-trained athletes, such as cyclists and rowers (132) (133).

Conclusion

Beta-alanyl-L-histidine (Carnosine) is one of the active QoL Enhancer ™ ingredients in the proprietary Molecular Action Blend ™ of  Ypera ®.

Beneficial Effects:

  • Prevention of muscle damage (105, 115, 134, 135)
  • Muscle nutrition while performing (105, 124, 132)
  • Anti-oxidative effect (105, 132, 136, 137)
  • Enhances cognitive capacity (105, 134)
  • Alzheimer’s disease (119)
  • Anti-aging (105, 138)
  • Heart damage (135)
  • Cancer-prevention (105, 114, 115)
  • Diabetes Mellitus (114, 138)
  • Eyesight (139)
  • Kidney disease (140)
  • Neurological disorders (105, 134, 141)

Abbreviations

Carnosine (Beta-alanyl-L-histidine)

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