Histidine found in protein, function and role
November 25 2015 by
Ray Sahelian, M.D.

L Histidine is an amino acid and is one of the 22 most common natural amino acids present in proteins. In humans, histidine is considered an essential amino acid, but mostly in children.

Carnosine (β-alanyl-l-histidine) was discovered in 1900 as an abundant non-protein nitrogen-containing compound of meat. The dipeptide is not only found in skeletal muscle, but also in other excitable tissues. Most animals, except humans, also possess a methylated variant of carnosine, either anserine or ophidine/balenine, collectively called the histidine-containing dipeptides.

Diabetologia. 2013. Histidine supplementation improves insulin resistance through suppressed inflammation in obese women with the metabolic syndrome: a randomised controlled trial.

L Histidine -rich glycoprotein  is an abundant plasma glycoprotein that has a multidomain structure, interacts with many ligands, and has been shown to regulate a number of important biological processes. Histidine -rich glycoprotein ligands include Zn(2+) and haem, tropomyosin, heparin and heparan sulphate, plasminogen, plasmin, fibrinogen, thrombospondin, IgG, FcgammaR and complement. In many cases, the histidine -rich region of the molecule enhances ligand binding following interaction with Zn(2+) or exposure to low pH, conditions associated with sites of tissue injury or tumour growth. The multidomain nature of Histidine -rich glycoprotein indicates that it can act as an extracellular adaptor protein, bringing together disparate ligands, particularly on cell surfaces. Histidine -rich glycoprotein binds to most cells primarily via heparan sulphate proteoglycans, binding which is also potentiated by elevated free Zn(2+) levels and low pH. Recent reports have shown that Histidine -rich glycoprotein can modulate angiogenesis and additional studies have shown that it may regulate other physiological processes such as cell adhesion and migration, fibrinolysis and coagulation, complement activation, immune complex clearance and phagocytosis of apoptotic cells.

L Histidine and lysine are two representative targets of oxidative modifications. Histidine is extremely sensitive to a metal-catalyzed oxidation, generating 2-oxo-histidine and its ring-ruptured products, whereas the oxidation of lysine generates carbonyl products, such as aminoadipic semialdehyde.

Histidine decarboxylase (HDC), the rate-limiting enzyme for mammalian histamine synthesis.

The existence of protein kinases, known as histidine kinases, which phosphorylate their substrates on histidine residues has been well documented in bacteria and also in lower eukaryotes such as yeast and plants. Their biological roles in cellular signalling pathways within these organisms have also been well characterised. The evidence for the existence of such enzymes in mammalian cells is much less well established and little has been determined about their cellular functions.

Q. What do you think of a l histidine supplement?
   A. I'm still not sure whether taking a histidine supplement could lead to allergic symptoms since histidine converts into histamine.

Q. Some people (myself!) get an allergic response (sinus problems, skin rash) to oral carnosine at 500-1000mg,
   A. Carnosine converts into histidine which converts into histamine. Perhaps too high of a carnosine dose can shift the metabolic pathway towards histamine.