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Writer's pictureRajlaxmi Baswanti

HISTIDINE - AN ESSENTIAL AMINO ACID


 

Formula: C6H9N3O2

Molar mass:155.1546 g/mol

 

Histidine or L- Histidine is an essential amino acid that the human body requires carrying unique physiological properties that helps the human body grow and function efficiently. To understand L Histidine we must first know about Amino Acid.

Amino acids are molecules that are combined to form proteins. It is used by all living things for the generation of proteins. Amino Acids play a vital role in body functions as a biological buffer, for nitrogen storage, and the formation of various other compounds.

There are two types of amino acids

  1. Essential amino acids: They are not produced by our human body, they can only be acquired through the diet.

  2. Nonessential amino acids: They are produced by the body itself.

L-Histidine is one of the essential amino acids. If we see L-HIS chemically it contains an Alpha-amino acid group, a carboxylic acid group and an imidazole side chain. During a chemical reaction in the body, the alpha amino group goes under protonation while the carboxyl group is deprotonated. Lastly, an imidazole ring is responsible for the proton buffering, metal ion chelating and exerts antioxidant properties.


Daily intake of L Histidine

The recommended daily intake of L Histidine is:

​For adults (19 years)

​11mg/kg/day

​For older

​ 14mg/kg/day

Role of L-histidine in the human body:

L-Histidine has several functions in the body, these are some key functions which have major assistance in the maintenance of the body.


Metal Binding:

The imidazole ring of histidine contains a nitrogen atom that can act as a ligand for metal ion binding. Because of this feature, histidine becomes essential for metalloprotein tasks such as carrying and storing metal ions such as iron and zinc.


pH regulation:

Histidine's imidazole side chain is unique among amino acids in that it can exist in two states: protonated (positively charged) and unprotonated (neutral). Because of this feature, histidine can act as a buffer in maintaining the pH equilibrium of cells and body fluids.


Synthesis of Histamine:

Histidine is a precursor of histamine. It is a neurotransmitter that is released in response to allergic reactions and is associated with inflammatory responses.


As a biomarker for skeletal muscle tissue:

Histidine is converted into 3-methylhistidine which is a biomarker in the damage of skeletal muscle tissue. This is conducted by methyltransferase enzymes. It Contributes to muscle development and repair. It aids in the synthesis of new muscle proteins as well as tissue upkeep.


Detoxification of body:

Histidine is also involved in the detoxification of heavy metals in the body, which helps to limit their negative effects.Histidine aids in the detoxification of heavy metals in the body via the chelation process. Chelation is a chemical reaction that occurs when a chelating substance, in this case histidine, binds to metal ions and creates stable complexes that are expelled from the body. When histidine binds to metal ions, stable complexes known as chelates form. These chelates are water-soluble and quickly removed from the body via urine. Chelation stops metal ions from interacting with other molecules in the body, hence lowering their toxicity.


Formation of Carnosine:

Carnosine is abundant in skeletal muscles and the brain and serves a variety of physiological activities. Carnosine helps maintain the acid-base balance in muscle cells during hard exercise by contributing to intracellular pH regulation. It also functions as an antioxidant, shielding cells from oxidative damage and possibly lowering muscle tiredness.

Let us understand How histidine forms carnosine? It is a chemical reaction happening inside the body, the steps and mechanism is mentioned below,

Combination of Histidine and Beta-Alanine: A condensation event between histidine and beta-alanine produces carnosine. One of the two amino acid units necessary for carnosine synthesis is histidine.

Carnosine Synthase Enzyme: Carnosine synthase is an enzyme that catalyzes the condensation process between histidine and beta-alanine ( for every reaction to happen enzymes are necessary. They act as catalysts that improve the rate of reaction as well as they act as signaling messengers for a function to start). This enzyme joins the two amino acids and helps the creation of a peptide bond, resulting in the synthesis of the carnosine molecule.

During the condensation reaction: The amino group (-NH2) of the histidine molecule combines with the carboxyl group (-COOH) of the beta-alanine molecule to form dipeptides. The removal of water (H2O) and the formation of a peptide bond between the two amino acids occur as a result of this reaction.


Histidine and oxygen supply the body:

Histidine is required for the synthesis of hemoglobin, the protein that transports oxygen in red blood cells. The chemical process of histidine in the body is explained below,

Synthesis of Hemoglobin: Histidine is an important component in the construction of hemoglobin, the protein that binds to oxygen in the lungs and releases it in the tissues. Hemoglobin is made up of four protein subunits, each of which contains a heme group. An iron ion in the heme group bonds to oxygen. Histidine is an amino acid that surrounds and interacts with the iron ion in the heme group, assisting in the stabilization of oxygen binding.

When oxygen levels are high, such as in the lungs, the iron ion in hemoglobin's heme group attaches to oxygen. The presence of histidine aids in the maintenance of the appropriate geometry and stability of the iron-oxygen link, ensuring efficient oxygen binding and release by hemoglobin. Because histidine interacts with the iron ion in hemoglobin, oxygen molecules can connect to the heme group. Because this interaction is reversible, hemoglobin releases oxygen in tissues with low oxygen concentrations, such as muscles and organs. This guarantees that oxygen is distributed properly to cells throughout the body.


Histidine and RBC formation:

RBCs as red blood cells are formed by a process known as ‘Erythropoiesis". Histidine plays a vital role in the Hb formation that results in the well-maintenance of red blood cells and the process of Erythropoiesis.

Intracellular Synthesis: Carnosine synthesis occurs primarily within cells, most notably in muscle tissue. Carnosine production requires the presence of both histidine and beta-alanine within the cells.

Summarizing the key functions of L-histidine, it is involved in the processes like cognitive function, appetite regulation and wakefulness.


Deficiency of Histidine:

The deficiency of histidine occurs rarely. Histidinemia is a rare inherited metabolic condition in which the body's capacity to break down and metabolize the amino acid histidine is impaired. A lack of the enzyme histidase, which is responsible for breaking down histidine into other chemicals that may be metabolized and removed from the body, causes this condition.

Symptoms:
  • Language and speaking problems

  • hyperactivity

  • Neurological imbalance - learning disability, growth delays etc

  • Frequent seizure attacks

Treatment:

Histidinemia is often detected during newborn screening or through genetic testing. Early detection and care, including dietary changes, can help decrease the disorder's potential detrimental effects and enhance the quality of life for those with histidinemia.


How to maintain L-histidine daily intake?

Histidine levels can be maintained with the help of proper diet and supplements.

If you have histidine deficiency disorder then, the parenteral injections are available when you are under doctor’s surveillance.

Sources of Animal Protein:

  • Meat options include hog, lamb, and other red meats.

  • Poultry: chicken, turkey, duck, and so on.

  • Tuna, salmon, sardines, haddock, and so on.

  • Seafood: Shrimp, crab, lobster, and so forth.

  • Eggs, especially egg whites.

Milk and dairy products:

  • Milk: This category includes both cow's milk and alternatives such as almond, soy, or oat milk.

  • Cheddar, mozzarella, Swiss, and more types of cheese are available.

  • Yogurt can be regular or Greek.

Plant-Based Ingredients:

  • Legumes include lentils, chickpeas, black beans, kidney beans, and other legumes. Spinach,Potatoes, Corn, Mushrooms,

  • Pumpkin seeds, sunflower seeds, chia seeds, flaxseeds, almonds, and other seeds and nuts.

  • Quinoa: A complete protein source including histidine. Brown rice, whole wheat, oats, and other whole grains.

  • Soy protein isolate, dried-frozen tofu, defatted soy flour and soy meal, soybeans, full-fat soy flour are all examples of soy products.

  • Mustard seeds, dried parsley, dried basil, dried spearmint, curry powder, and garlic powder

Histidine supplements

  • Histidine is supposed to be consumed throughout the diet. Short-term use of histidine supplements may be safe.

  • Doses of up to 4 grams per day have been successfully used for up to 12 weeks. It seemed to be highly received.

  • A well-balanced diet will provide enough histidine for the majority of people. Histidine supplements are generally not suggested for most healthy persons who eat a well-balanced diet.

  • Individual amino acid supplements containing histidine are available, however, they are not generally used or suggested except under the supervision of a healthcare expert.


NOTE: It is critical to check with a healthcare physician before contemplating any supplements, especially if you have specific health concerns or illnesses. Excessive use of individual amino acid supplements might upset the body's amino acid balance and have unforeseen health consequences.


Metabolism of L-Histidine:

As per the daily intake of Histidine, we need to consume 11-14 mg per day.Let us understand how this histidine is metabolized in the body via different organs. As we know, metabolism has two phases i.e. Catabolism ( it is a process that break down larger molecules into smaller ones in order to produce energy and anabolism

As we have L histidine from diet it also needs to be degraded from the body. With the following mechanism, Histidine is catabolized. The pathway for histidine catabolism begins with the deamination of catalyzed histidase that produces trans-urocanate and ammonia. The enzyme is located in the liver and stratum corneum of the skin.



REFERENCES:


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