BIOCHEMISTRY - Textbook - Ostapchenko L. I. - 2012

Chapter 6. AMINO ACID METABOLISM AND FUNCTIONS. PROTEIN BIOSYNTHESIS

6.9. Nitrogenous Compounds — Amino Acid Derivatives

6.9.2. Nitrogenous Compounds — Histidine Derivatives

In various Tissues, The amino acid Histidine is acted upon by different Enzymes and enters two distinct metabolic pathways:

✵ Catabolism to end products;

✵ synthesis of histamine.

In The Liver and Skin, histidine undergoes deamination catalyzed by the enzyme histidase, yielding urocanic acid (Fig. 6.31). The End products of Histidine METABOLISM are glutamate, NH₃, and H₄-folate derivatives (N⁵-formimino-H₄-folate and N¹⁰-formyl-H₄-folate). A hereditary deficiency of histidase leads to histidine accumulation and The Development of histidinemia, which manifests as delayed mental and physical development in children. A hereditary deficiency of liver Urocanase can cause urocanemia, resulting in elevated levels of urocanate in the Blood. The symptoms of this pathological condition share many features with other enzymopathies and are manifested by retarded mental and physical development.

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Fig. 6.31. Scheme of histidine metabolism in various tissues

The enzymes histidase and urocanase are hepatospecific; therefore, their assay is used clinically to diagnose liver damage.

Histamine is produced by the decarboxylation of histidine in mast Cells of Connective Tissue:

Histamine forms complexes with Proteins and is stored in the secretory granules of mast cells. It is secreted into the blood As a result of tissue damage (trauma, burn, exposure to endo- and exogenous substances), as well as immune and allergic reactions. Histamine performs the following Functions in The Human Body:

✵ stimulates the secretion of gastric juice and saliva (thus acting as a digestive hormone);

✵ increases capillary permeability, causes edema, lowers blood pressure (while increasing intracranial pressure and causing headaches);

✵ constricts smooth Muscles of the Lungs, causing asphyxia;

✵ participates in the development of inflammatory responses by causing vasodilation, skin redness, and tissue edema;

✵ triggers allergic reactions;

✵ acts as a neurotransmitter;

✵ serves as a pain mediator.

The histidine dipeptides Carnosine and Anserine are synthesized in muscles and the Brain, with particularly high concentrations in skeletal muscles reaching 100–200 mg/100 g of tissue. Carnosine was discovered by the Russian biochemist V. S. Gulevich in 1900, and anserine was identified somewhat later.

Carnosine is synthesized from β-Alanine and histidine under the action of carnosine synthetase:

Subsequently, in the presence of SAM, carnosine undergoes methylation catalyzed by N-methyltransferase to form anserine. The β-alanine required for this synthesis is produced during the Catabolism of pyrimidine NUCLEOTIDES.

Carnosine can enter the bloodstream from muscles and be absorbed by the Kidneys and enterocytes. Human blood and kidneys contain a Zn-dependent enzyme, carnosinase, capable of hydrolyzing carnosine into β-alanine and histidine.

The Physiological effects of histidine dipeptides were studied by the Russian biochemist S.E. Severin in the 1960s and continue to be investigated by many scientists to this day. Carnosine increases the contraction amplitude of skeletal muscles, activates the operation of Muscle Cell ion pumps, and stimulates the ATPase activity of Myosin. The content of histidine Peptides in smooth and cardiac Muscle Tissues is many times lower than in Skeletal Muscle. They account for up to 40% of the buffer capacity of fast-twitch muscles and allow for the accumulation of large amounts of lactate, the excess of which, in the absence of histidine peptides, leads to acidosis and contracture. Carnosine and anserine exhibit antioxidant activity, inhibit NO-dependent guanylyl cyclase, and slow down human Aging processes by influencing The rate of apoptosis.