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Histidine

Amino acids are organic compounds containing both amino group and carboxylic acid group in the same compound. If the amino group and carboxylic acid group are attached to the same carbon atom then they are classified as α-amino acids. There may be more than one amino group and carboxylic acid group in an amino acid.

The number of carboxylic acid group and amino group determines the pKa value of amino acid. Similarly there may be some other functional groups like imidazaole and other nitrogeneous groups may also present and determine the pKa value. Except glycine all other amino acids are optically active. They rotate the plane polarized light in specific direction.
The pair of dextro and laevo rotatory compounds of the same compound are called as enantiomers. Out of the two enantiomer one alone will be biologically important as it can interact with biological systems effectively.

 

Histidine Structure

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Histidine is an alpha amino acid with imidazole functional group having the molecular formula C6H9N3O2. The structural formula of histidine is given as

Histidine Structure

The structure contains an amino group and carboxylic acid group in the the same carbon atom and an imidazole ring in the β position. Due to the presence of imidazole ring histidine is basic in nature. The imidazole ring is aromatic in nature with 6 $\pi $ electrons. In the strong acid solutions the imidazole ring is protonated and there are two N-H bonds in the ring. The imidazole side chain is strong ligand and is used to coordinate in metal proteins.
As the histidine structure is mostly protonated in the imidazole ring, it is common to represent the general structure of histidine as protonated in the nitrogen atom. But this ion is stabilized by resonance and the overall resonance structures are given as
Resonance Structure of Histidine

Hence there exists a tautomerism of shift in hydrogen attached with nitrogen through the cation formation in the solution. This is schematically explained here.

Tautomerism

The above conclusion can be supported by NMR studies. At lower pH the N chemical shifts are indistinguishable. When the pH increases, at nearly 8 the protonation is lost.

Hence there is two distinguishable shifts are observed for nitrogen and the studies shown that N1-H tautomer is preferred over N3-H tautomer. However complete deprotonation of histidine is possible only at pH of above 14 which is not relevant.

L-Histidine

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L- Histidine is one of the optical isomer (enantiomer) of Histidine which is biologically important. It is the starting material for histamine which is associated with allergy producing symptoms. Histamine will increase the inflammatory response of skin and mucous membranes. This inflammatory action of histamine is essential during severe infection like cold etc. The structure of L-Histadine is given herewith.

L-Histidine

It may be noted that the position of H and NH2 will be exchanged in D-histidine which is not that much importance in biological activities.

Histidine Synthesis

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  1. Histidine is non essential amino acid which is required a little for children but produced from other sources and amino acids.
  2. But it should be supplied in moderate quantities to the population with deficiency symptoms.
  3. The nitrogen atoms in the histidine (both at imidazole ring and at amino group) can be protonated and released at specific pKa values.
  4. Hence histidine is used as proton shuttle in metabolism.
  5. Histidine is useful in hemoglobin as it stabilizes oxyhemoglobin then carbonyl hemoglobin.
  6. So the stability of carboxy hemoglobin is relatively decreased in our blood.

Histidine pKa

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There are one amino group and one carboxylic acid group in histidine. Apart from this there is one imidazole ring with basic nitrogen. Hence imidazole is overall basic in nature. The pKa of imidazole ring is approximately 6.0 while that of the entire compound is 6.5. In strong acid solution it will exist as cation form.

Histidine Protonation

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Histidine molecule can easily be protonated at two points. One is at the amino group in the alpha carbon and the other point is at the nitrogen atom in the imidazole ring. Hence it is strong ligand capable of donating electrons and this property is used in binding of metal proteins. This property is used to rapidly remove proton from zinc bound water molecule to restore the active site of enzyme.

Histidine Metabolism

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Histidine is useful in the synthesis of histamine. It undergoes decarboxylation reaction with histidine decarboxylase to give histamine.

Metabolism of Histidine
Similarly it is converted to ammonia and urocanic acid by histidine ammonia-lysase.

Histidine Uses

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It is useful in the synthesis of many metal containing proteins like hemoglobin, Metals like copper, iron, zinc are transported by binding with histidine and hence it is essential for excretion of excess metals from our body.

L-Cystein and L-Histidine are important in protecting the metals in the original form in our body without any oxidation. It is useful for the healthy functioning of hemoglobin as it destabilizes carboxy hemoglobin and stabilizes oxyhemoglobin.

Histidine and Histamine

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  • Histamine is an organic nitrogen compound having the structure analogous to histidine.
  • It is synthesized within our body by the decarboxylation of histidine by histidine decarboxylase.
  • It initiates the inflammatory response during the response to foreign pathogens and it increases the permeability of blood capillaries to while blood cells and some other proteins so that they can reach the affected part easily. It is also working as a neurotransmitter.
  • It is continuously generated at mast cells and basophiles (blood white cells)

Histamine Uses

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  1. As a neurotransmitter histamine regulates sleep. Hence we feel drowsy when we take antihistamines for some allergic reactions like running nose. Studies revealed that irregular levels of histamine will affect the cognitive ability of persons.
  2. It is also also used in gastric system by controlling the amount of stomach pile secreted.
  3. The symptoms produced by histamine towards allergy producing substances are clear and measurable. Hence it can also be used to detect the allergic response of the skin to certain allergy inducing substances.
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