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Histidine
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Histidine (abbreviated as His or H) is one of the 20 standard amino acids present in proteins. In the nutritional sense, in humans, histidine is considered an essential amino acid, but only in children. After a human is a few years old, the human will start to produce this amino acid, thus making it a non-essential amino acid. Its codons are CAU and CAC.
Histidine was first isolated by German physician Albrecht Kossel in 1896.
imidazole sidechain of histidine has a pKa of approximately 6, and overall, the amino acid has a pI of 7.6.
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Histidine (abbreviated as His or H) is one of the 20 standard amino acids present in proteins. In the nutritional sense, in humans, histidine is considered an essential amino acid, but only in children. After a human is a few years old, the human will start to produce this amino acid, thus making it a non-essential amino acid. Its codons are CAU and CAC.
Histidine was first isolated by German physician Albrecht Kossel in 1896.
Chemical properties
The imidazole sidechain of histidine has a pKa of approximately 6, and overall, the amino acid has a pI of 7.6. This means that at physiologically relevant pH values, relatively small shifts in pH will change its charge. Below a pH of 6, the imidazole ring is fully protonated and bears two NH bonds. The positive charge is equally distributed between both nitrogens and can be represented with two equally important resonance structures. As expected, the 15N chemical shifts of these nitrogens are indistinguishable (About 200 ppm relative to nitric acid). As the pH increases to approximately 8, the protonation of the imidazole ring is lost. The remaining proton of the now neutral imidazole can exist on either nitrogen, giving rise to what are known as the N-1 or N-3 tautomers. NMR shows that the chemical shift of N-1 drops slightly, while the chemical shift of N-3 drops considerably (about 190 vs. 145 ppm). Because these chemical shifts are relative to nitric acid, a substance which resonantes far downfield, a decrease in chemical shift corresponds to deshielding. This indicates that the N-1-H tautomer is preferred, presumably due to hydrogen bonding to the neighboring ammonium. The shielding at N-3 is substantially reduced due to the second-order paramagnetic effect, which involves a symmetry-allowed interaction between the nitrogen lone pair and the excited pi* states of the aromatic ring. As the pH rises above 9, the chemical shifts of N-1 and N-3 become approximately 185 and 170 ppm. It is worth noting that the deprotonated form of imidazole, imidazolate ion, would only be formed above a pH of 14, and is therefore not physiologically relevant. This change in chemical shifts can be explained by the presumably decreased hydrogen bonding of an amine over an ammonium ion, and the favorable hydrogen bonding between a carboxylate and an NH. This should act to decrease the N-1-H tautomer preference.
For more information, see "ABCs of FT-NMR" by John D. Roberts, page 258-259.
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.
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 doesn't absorb at 280nm in either state, but does in the lower UV range more than some amino acids .
Metabolism
The amino acid is a precursor for histamine and carnosine biosynthesis.
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.
Supplementation
Supplementation of Histidine has been shown to cause rapid zinc excretion in rats with an excretion rate 3 to 6 times normal. Some people take histidine in an attempt to raise their histamine levels. Histamine is released under conditions of higher osmolality (dehydration/salt). Raising histamine may be more effective by adapting the body to a higher osmolality by eating sodium without greatly increasing water intake and taking supplements that help the body adapt to those conditions (zinc/taurine/B1/B12). Histidine supplementation likely tricks the body into believing it is producing less histamine and assumes it is well or overhydrated and is better off without the nutrients used to maintain cellular hydration in a hyperosmotic state. Histidine supplementation however is inadvisable because one of the hallmarks of today's chronic diseases (diabetes, Alzheimer's, Parkinson's) is zinc depletion.
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