Histidine

It contains an α-amino group (which is in the protonated –NH3+ form under biological conditions), a carboxylic acid group (which is in the deprotonated –COO− form under biological conditions), and an imidazole side chain (which is partially protonated), classifying it as a positively charged amino acid at physiological pH.

The conjugate acid (protonated form) of the imidazole side chain in histidine has a pKa of approximately 6.0.

The remaining proton of the imidazole ring can reside on either nitrogen, giving rise to what are known as the N3-H or N1-H tautomers.

[9] The acid-base properties of the imidazole side chain are relevant to the catalytic mechanism of many enzymes.

[10] In catalytic triads, the basic nitrogen of histidine abstracts a proton from serine, threonine, or cysteine to activate it as a nucleophile.

The tautomerism and acid-base properties of the imidazole side chain has been characterized by 15N NMR spectroscopy.

This change indicates that the N1-H tautomer is preferred, possibly due to hydrogen bonding to the neighboring ammonium.

The shielding at N3 is substantially reduced due to the second-order paramagnetic effect, which involves a symmetry-allowed interaction between the nitrogen lone pair and the excited π* states of the aromatic ring.

Poly-histidine tags (of six or more consecutive H residues) are utilized for protein purification by binding to columns with nickel or cobalt, with micromolar affinity.

[15] Histidine is synthesized from phosphoribosyl pyrophosphate (PRPP), which is made from ribose-5-phosphate by ribose-phosphate diphosphokinase in the pentose phosphate pathway.

The first reaction of histidine biosynthesis is the condensation of PRPP and adenosine triphosphate (ATP) by the enzyme ATP-phosphoribosyl transferase.

[18] A genetic study of N. crassa histidine mutants indicated that the individual activities of the multienzyme complex occur in discrete, contiguous sections of the His-3 genetic map, suggesting that the different activities of the multienzyme complex are encoded separately from each other.

[18] However, mutants were also found that lacked all three activities simultaneously, suggesting that some mutations cause loss of function of the complex as a whole.

[22] The Food and Nutrition Board (FNB) of the U.S. Institute of Medicine set Recommended Dietary Allowances (RDAs) for essential amino acids in 2002.

[29] Supplemental histidine is being investigated for use in a variety of different conditions, including neurological disorders, atopic dermatitis, metabolic syndrome, diabetes, uraemic anaemia, ulcers, inflammatory bowel diseases, malignancies, and muscle performance during strenuous exercise.

NFPA 704 four-colored diamond Health 1: Exposure would cause irritation but only minor residual injury. E.g. turpentine Flammability 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g. canola oil Instability 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogen Special hazards (white): no code
Histidine ball and stick model spinning
The histidine-bound heme group of succinate dehydrogenase , an electron carrier in the mitochondrial electron transfer chain . The large semi-transparent sphere indicates the location of the iron ion . From PDB : 1YQ3 ​.
The tricopper site found in many laccases , notice that each copper center is bound to the imidazole sidechains of histidine (color code: copper is brown, nitrogen is blue).
Histidine Biosynthesis Pathway Eight different enzymes can catalyze ten reactions. In this image, His4 catalyzes four different reactions in the pathway.
Conversion of histidine to histamine by histidine decarboxylase
Unspecified L-amino acid