단백질 ≫ 아미노산 ≫ 아미노산 합성

이미다졸 디펩타이드 imidazole dipeptide

- histidine
- 이미다졸 디펩타이드

Carnosine, anserine, balenine and homocarnosine are imidazole dipeptides found exclusively in animal tissue, especially in skeletal muscle and nerves. These compounds exist as an equilibrium of two tautomeric structures of their imidazole ring, known as Nτ-H and Nπ-H, usually shifted towards the former tautomer. While terrestrial mammals and amphibians contain mostly carnosine, anserine predominates in fish and birds, and balenine in reptiles and cetaceans. The imidazole ring of these peptides is fairly prone to electrophilic attack at the imine nitrogen, but it is much less likely to undergo a nucleophilic substitution reaction unless the ring is activated by strongly electron-withdrawing groups. Synthesis of imidazole peptides is usually done by chemical routes, but enzymatic approaches are being increasingly used, especially due to their higher specificity and lower environmental impact. Imidazole dipeptides play an important role as intracellular buffers in vertebrate muscle (up to 60% of buffering capacity) due to their pK values, which are close to physiological pH, a theory known as "alphastat regulation". Moreover, carnosine and anserine show in vivo antioxidant activity through metal-chelating and free-radical scavenging mechanisms.

Carnosine, anserine, balenine 및 homocarnosine은 동물 조직, 특히 골격근과 신경에서만 발견되는 이미다졸디펩티드다. 이 화합물은 Nut-H와 Nπ-H로 알려진이 두 가지 형태를 가진다. 육지 포유류와 양서류는 주로 Carnosine이 포함되어 있지만 anserine은 물고기와 새에서 주로 발생하며 파충류와 고래류에서는 balenine이 많다. 이러한 펩타이드의 이미다졸 고리는 이민 질소에서의 친 전자성 공격을 받기 쉽지만, 고리가 강하게 전자 흡인 그룹에 의해 활성화되지 않는다면 친핵성 치환 반응을 거치지는 않는다.
이미다졸 디펩티드는 "alphastat regulation"으로 알려진 이론 인 생리적 pH에 가까운 pK 값으로 인해 척추 근육에서 세포 내 완충제 (완충 능력의 60 %까지)로 중요한 역할을 한다. 또한, 카르노신 및 안세린은 금속 킬레이트 및 자유 라디칼 소거 메카니즘을 통해 생체 내 항산 활성을 나타낸다.

 


 

 

 

● Carnosine is a dipeptide consisting of l-histidine and β-alanine and is present in millimolar concentrations in human skeletal muscles.
● Most animals, except humans, also possess a methylated variant of carnosine, either anserine or ophidine/balenine, collectively called the histidine-containing dipeptides.
● Within-subject muscle-carnosine levels are quite stable, while a relative large between-subjects variation exists.
● Young, male subjects with a high proportion of fast-twitch muscle fibers have the highest carnosine concentration within a healthy population.
● An excess dietary intake of β-alanine (1.6–6.4 g per day) for several weeks (2–10 weeks) results in 1.3- to 2-fold higher muscle carnosine stores.
● β-Alanine is a popular nutritional supplement amongst athletes as it has been shown to improve some high-intensity exercise performances that last at least 1 min.
● As its dissociation constant is ideal (pKa 6.83) and as the carnosine content is positively correlated to the buffering capacity, it is generally
accepted that carnosine can act as a pH buffer in humans.
● In vitro data on both single fibers and intact muscles further suggest that carnosine can improve calcium handling during muscle contraction.
● Although more research is needed, several suggestions have been made that carnosine can be released from skeletal muscle into the interstitium and that it further acts as depot for the histidine–histamine pathway during periods of increased demands.

Intramyocellular Buffering
The accumulation of intracellular protons during high-intensity exercises can be counteracted by different proton-buffering systems, e.g. inorganic phosphate, proteins, histidine-containing dipeptides, bicarbonate and phosphocreatine. Of all the amino acids, histidine is the only one with a pKa value (= 6.1) in the range of the physiological pH of the muscle (i.e. 7.0–6.0).
When bounded together with β-alanine to form carnosine, the pKa value of the imidazole ring of histidine increases to 6.83 (Bate Smith, 1938). Next to an ideal pKa value, also a high intramuscular concentration is contributing to the buffering capacity of this dipeptide.
The contribution of carnosine to the total intracellular muscle buffering capacity is dependent on its concentration and thus on the species and muscle type under investigation. The contribution of HCDs to the total muscle-buffering capacity accounts, for example, for 23% in chicken, 25% in whale and 40% in skipjack tuna skeletal muscle (Abe, 2000). In humans, muscle contains a smaller amount of carnosine, which results in relatively lower contributions of 4.5% and 9.4% in type I and II fibers of vastus lateralis (Mannion et al., 1992). Not only between but also within species there is a positive correlation (0.34 < r < 0.69 for humans, r = 0.67 for horses) between HCD content and muscle-buffering capacity (Parkhouse et al., 1985; Sewel et al., 1992; Baguet et al., 2011a).
Despite these clear, but indirect, evidences for the role of carnosine as buffering agent, only 2 intervention studies have investigated the effect of muscle-carnosine loading on proton accumulation during high-intensity exercise. Baguet and colleagues showed that the blood pH decline following a 6 min high-intensity cycling exercise bout was attenuated following longterm β-alanine supplementation compared to control (Baguet et al., 2010b).
On the other hand, carnosine loading (+24%, +1.8 mmol kg−1 WW) following β-alanine supplementation (38 days, 3.2 g per day) was not able to attenuate the decline in vastus lateralis pH (from 7.01 to 6.76) during 90 s high-intensity cycling (Gross et al., 2013). In contrast to the hypothesis, muscle-buffering capacity was also not affected by β-alanine supplementation. As β-alanine enhanced the aerobic energy contribution and decreased the O2 deficit and muscle lactate accumulation during 90 s severe cycling, the authors hypothesized that the improved capacity for severe exercise after β-alanine supplementation could be due to mechanisms other than proton buffering (Gross
et al., 2013). To conclude, further research on human muscle samples during  high-intensity exercise is definitely required to validate the theoretical rationale of carnosine’s buffering function.


히스티딘의 기능
근육을 구성하는 성분 중 하나인 카르노신에 쓰이기 때문에 단백질 보충제에 포함되어 있는 경우가 많다. 또한 위액 분비 촉진, 혈구 생성, 관절염 및 알레르기 증상 개선, 신경세포 보호, 중금속 및 방사선에 대한 저항력 증가 등의 기능이 알려져 있다.
또한 많은 효소의 활성 부위에는 히스티딘이 존재해 효소 반응에 중심적인 역할을 한다. 이는 히스티딘의 곁가지에 달려 있는 이미다졸(imidazole) 고리 때문이다. 이미다졸 고리의 두 개의 질소 원자는 모두 양이온를 받았다가 내놓았다가를 할 수 있으며, 또한 이 이미다졸의 작용기 pKa가 7에 근접하기 때문에 중성인 체내에서 약간의 변화만 가해도 H+의 해리를 쉽게 조절할 수 있다. 이를 통해 효소는 기질에 H+를 주거나 가져가는 과정을 효과적으로 촉매할 수 있게 된다.