INTRODUCTION
Over 600 inherited metabolic disorders, including hereditary disorders of amino acid metabolism (histi-dinemia, phenylketonuria, tyrosinemia, alkaptonuria, and others), have been identified to date. Diseases associated with disturbed amino acid metabolism develop if the activity of an enzyme involved in the metabolism of ingested amino acids is selectively reduced. These diseases affect the central nervous system, resulting in mental retardation with motor and speech defects, impaired vision and hearing, emotional and behavioral disorders, and seizures [1, 4].
Hereditary metabolic disorders are caused by mutations introducing changes into the nucleotide sequence of genomic DNA. Mutations result in the synthesis of abnormal proteins (including structural proteins, enzymes, hormones, growth factors, and receptor proteins). For instance, if the mutation affects a gene encoding an enzyme, the latter loses its catalytic activity partially or completely [2, 21]. The vast majority of hereditary metabolic disorders is caused by genetic defects affecting enzymes involved in the metabolism of amino acids, carbohydrates, and lipids. Pathogenesis and clinical manifestations are determined by the lack of normal metabolites (intermediate or final) and the ac-cumulation of toxic metabolites. The clinical presentation largely depends on the degree of the mutant gene expression, as well as on other genetic factors and environmental conditions. Mental retardation and neurological disorders are among the most frequent and severe consequences of the biochemical defect in the majority of patients [3, 5, 17].
Total screening for histidinemia, an innate defect of amino acid metabolism, in newborn babies has been recently introduced in Russia. Histidinemia is a hereditary disease associated with a disturbance of the metabolism of the amino acid histidine. The disease is a congenital defect of histidine-ammonia-lyase, an enzyme that belongs to the lyase class (EC 4.3.1.3, gene HAL, 12q22-q23) and catalyzes the deamination of L-histidine to form urocanic acid and ammonia. Histidine (L-α-amino-β-imidazolylpropionic acid) is an essential amino acid which must be present in the diet of young children. Besides, a histidine residue is often present in the active centers of enzyme molecules, and the biosynthesis of histamine in the human organism requires histidine as well. The metabolic block leads to accumulation of large amounts of histidine and the products of its abnormal metabolism (imidazolepyruvic, imidazolelactic, and imidazoleacetic acids) in the tissues and body fluids of the patient, this having a toxic effect on the central nervous system [8, 9, 14, 19, 24].
Diet therapy based on limiting the ingestion of histidine to a value that is the most appropriate for the individual metabolic requirements of the patient’s organism is the only efficient treatment for histidinemia currently available [6, 7, 13, 20].
The aim of the present work was to study histidine biotransformation in milk protein hydrolyzates treated by L-histidine-ammonia-lyase, to develop a technique for biotransformation, and to elaborate a procedure for the production of a milk protein concentrate for use in specialized dietary products.
