Download PDF

What is Histidine?

Histidine is an α-amino acid including the symbol "His" or 'H,' that is used in the biosynthesis of proteins. It holds a carboxylic acid group (in the deprotonated –COO− form under the biological conditions), α-amino group (in the form of protonated –NH3+, under biological conditions), and also an imidazole side chain (which is protonated partially), classifying it as a positively charged amino acid at the physiological pH. Initially, this acid thought was essential only for infants, but it has now been shown in longer-term studies to be essential for adults. Moreover, it is encoded by condoms, CAC, CAU.

Chemical Properties of Histidine

  • Histidine is an evident acid because it comprises the ring structure in its 'R' group by holding 2 nitrogen groups.

  • The histidine Chemical Structure can be given as C6H9N3O2.

  • An abbreviation that is used to represent this necessary amino acid is either 'H' or 'His.' In general, they are positively charged.


The imidazole chain is one of the elements of catalytic sites found in some enzymes, and it is taken as one of the most prevalent coordinating ligands present in metalloproteins. To activate it in catalytic triads as a nucleophile, basic histidine nitrogen is used to abstract a proton from a threonine, serine, and cysteine. Whereas in the proton shuttle case, it is used to shuttle the protons.


At every level of the ph-value, the imidazole ring of histidine results in aromatic. It holds 6 pi electrons, where 2 form a nitrogen lone pair and the other 4 forms 2 double bonds. It can lead to pi-stacking interaction formation, but it is hard because of the positive charges.

Benefits of Histidine

Let us look at the benefits of histidine.

  • L-Histidine can be said as a vital amino acid, which is required by the body primarily in the growing stage of children. Therefore, it is present in the form of supplementary or in food.

  • Different food products that include histidine are given as meat, fish, and dairy products.

  • It is also helpful to transfer a large amount of copper and iron.

  • It can control diarrhea because it boosts calcium absorption, thus decreasing the histidine level. However, excessive consumption would lead to a few side effects like constipation.

  • It contains a symbolic mechanism in preventing the clotting and internal bleeding of blood.

Role of Histidine in the Human Body

Nutritionally, histidine is a necessary amino acid that can also help as a precursor for various hormones (For example, the thyrotropin-releasing hormone), and also the critical metabolites affecting renal function, gastric secretion, neurotransmission, including the immune system. Its unique acid or base properties make it a versatile catalytic residue in various enzymes and those enzymes and proteins that coordinate the metal ions.


Histidine is one of the 9 important amino acids that humans must get to gain their diet, and it is available in most protein-rich foods like fish, meat, eggs, whole grains, soy, nuts, and beans. The histidine's imidazole side chain is unique amongst amino acids, giving rise to its amphoteric and aromatic properties at physiologic pH. Furthermore, this property makes it a key catalytic residue in several enzymes. It also performs an important anti-oxidant, anti-inflammatory, anti-secretory functions within the body.

Issues of Concern

A specific dietary intake of histidine is crucial, both during the development and throughout life. The histidine deficiencies and genetic defects in histidine metabolism as well can pose problems across different body systems. Notably, the metabolic byproducts are urocanic acid, histamine, and including muscle dipeptides like anserine and carnosine. Histamine is crucial as a neurotransmitter to modulating the inflammatory response and acid regulation, gastric as well. Urocanic acid (otherwise called urocanate) is vital to the formation of the epidermal barrier of the skin. It also contains links to UV light absorption, immunosuppression. Finally, muscle dipeptides, such as anserine and carnosine, play the roles of homeostatic regulators that protect tissues.


Histidine holds a diverse role in cellular function. Besides playing a catalytic and structural role in several enzymes, histidine residues are also allowed to undergo enzyme-catalyzed methylation (using S-adenosyl methionine as a methyl donor). Histidine residues are also a key to myelin sheath maintenance because they participate in the galactosylceramide hydroxylation, which is responsible for the myelin compaction.

The histidine metabolite carnosine (otherwise called beta-alanyl-L-histidine) also combats the intramuscular acidosis, maintaining an intracellular, extracellular buffering in the muscle tissue’s pH.


The importance of histidine to the human body derives from the properties that are described by its distinctive structure. Moreover, its side-chain is composed of an imidazole ring that is heterocyclic in nature and contains nitrogen atoms at position 1 (pi) and position 3 (tau). It is ionizable and exists both in protonated and neutral body forms, which gives histidine one pK and one pH unit below neutrality, allowing it to be acid & base at physiologic pH. Also, histidine's imidazole ring is defined as aromatic, which confers stability and makes it apolar at a physiologic pH.

Did You Know?

  • Amino Acids acidic due to the carboxyl group on 1 terminus, -COOH. The other terminus can be defined as an amine group or simply NH2-. Between these two, there is a volumetric side chain that defines which amino acid it is. The major story of amino acids relates to how they were discovered. If a protein is hydrolyzed, we get acidic, made of fragments and amino acids.

FAQ (Frequently Asked Questions)

1. Explain the TGA Role that Plays in the Human Body.

Answer: Triglyceraldehydes or triglycerides are very important.

  • They are fats that can be energy stores if much glucose or other sugars are consumed. Mostly, they can be stored in the adipose tissue under the skin.

  • They can also be turned into phospholipid by removing a fatty acid and adding a phosphate group to the rest of the 2 fatty acid chains. Phospholipids can make cell membranes and surround many cell organelles enabling chemical reactions to occur isolated from the environment.

2. Why is Histidine Considered as Basic Amino Acid and Tryptophan as a Neutral Amino Acid?

Answer: In the tryptophan case, the nitrogen lone pairs are delocalized, and they are part of an aromatic system. Therefore, that nitrogen is not basic enough, and hence it has a low “pKa” of around -3.8.

Whereas, in histidine, the nitrogen whose lone pair is not donated in the ring can be defined as basic enough.

3. What are Amino Acids?

Answer: Amino acids, together, combined with a peptide bond into the primary structure of a protein. This primary structure is referred to as a polypeptide chain. An amino acid is given as a form of a carboxyl group and an amino group.

Share this with your friends