Histidine

Histidine (abbreviated His or H) is an a-amino acid with an imidazole functional group. It is one of the 22 proteinogenic amino acids. Its codons are CAU and CAC. Histidine was first isolated by German physician Albrecht Kossel in 1896. Histidine is an essential amino acid in humans and other mammals. It was initially thought that it was only essential for infants, but longer-term studies established that it is also essential for adult humans. Its formula is C 6 H 9 N 3 O 2.  

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Histidine is an essential amino acid, manufactured in sufficient quantities in adults, but children may at some time have a shortage of this important vitamin. It is one of the basic (reference to pH factor) amino acids due to its aromatic nitrogen-heterocyclic imidazole side chain. This amino acid is metabolized into the neurotransmitter histamine and the set of genes that produce the enzymes responsible for histidine synthesis. ====== Histidine is also a precursor of histamine, a compound released by immune system cells during an allergic reaction.

It is needed for growth and for the repair of tissue, as well as the maintenance of the myelin sheaths that act as protector for nerve cells.

It is further required for the manufacture of both red and white blood cells, and helps to protect the body from damage caused by radiation and in removing heavy metals from the body.

In the stomach, histidine is also helpful in producing gastric juices, and people with a shortage of gastric juices or suffering from indigestion, may also benefit from this nutrient.



Chemical properties
The imidazole sidechain  of histidine has a pKa of approximately 6.0, and, overall, the amino acid has a pKa of 6.5. This means that, at physiologically relevant pH values, relatively small shifts in pH will change its average charge. Below a pH of 6, the imidazole ring is mostly protonated as described by the Henderson–Hasselbalch equation. When protonated, the imidazole ring bears two NH bonds and has a positive charge. The positive charge is equally distributed between both nitrogens and can be represented with two equally important resonance structures.

Biochemistry
The imidazole sidechain of histidine is a common coordinating [|ligand] in [|metalloproteins] and is a part of [|catalytic] sites in certain [|enzymes]. In [|catalytic triads], the basic nitrogen of histidine is used to abstract a proton from [|serine] , [|threonine] , or [|cysteine] to activate it as a [|nucleophile]. In a histidine [|proton shuttle], histidine is used to quickly shuttle protons, it can do this by abstracting a proton with its basic nitrogen to make a positively-charged intermediate and then use another molecule, a buffer, to extract the proton from its acidic nitrogen. In [|carbonic anhydrases], a histidine proton shuttle is utilized to rapidly shuttle protons away from a [|zinc] -bound water molecule to quickly regenerate the active form of the enzyme. Histidine is also important in [|haemoglobin] in helices E and F. Histidine assists in stabilising oxyhaemoglobin and destabilising CO-bound haemoglobin. As a result, [|carbon monoxide] binding is only 200 times stronger in haemoglobin, compared to 20,000 times stronger in free haem.

Aromaticity
The imidazole ring of histidine is aromatic at all pH values. It contains six pi electrons : four from two double bonds and two from a nitrogen lone pair. It can form pi stacking interactions, but is complicated by the positive charge. It does not absorb at 280 nm in either state, but does in the lower UV range more than some amino acids.

Biochemistry
The imidazole sidechain of histidine is a common coordinating ligand in metalloproteins and is a part of catalytic sites in certain enzymes. In catalytic triads, the basic nitrogen of histidine is used to abstract a proton from serine , threonine , or cysteine to activate it as a nucleophile. In a histidine proton shuttle, histidine is used to quickly shuttle protons, it can do this by abstracting a proton with its basic nitrogen to make a positively-charged intermediate and then use another molecule, a buffer, to extract the proton from its acidic nitrogen. In carbonic anhydrases, a histidine proton shuttle is utilized to rapidly shuttle protons away from a zinc -bound water molecule to quickly regenerate the active form of the enzyme. Histidine is also important in haemoglobin in helices E and F. Histidine assists in stabilising oxyhaemoglobin and destabilising CO-bound haemoglobin. As a result, carbon monoxide binding is only 200 times stronger in haemoglobin, compared to 20,000 times stronger in free haem.

Metabolism
The amino acid is a precursor for histamine and carnosine biosynthesis. Conversion of histidine to histamine by histidine decarboxylase The enzyme histidine ammonia-lyase converts histidine into ammonia and urocanic acid. A deficiency in this enzyme is present in the rare metabolic disorder histidinemia. In Actinobacteria and filamentous fungi, such as // Neurospora crassa //, histidine can be converted into the antioxidant ergothioneine.

Supplementation
Supplementation of Histidine has been shown to cause rapid zinc excretion in rats with an excretion rate 3 to 6 times normal.