EFFECT OF WHEY PROTEIN ON HEPATIC NITROGEN METABOLISM: MOLECULAR–METABOLIC MECHANISMS OF AMINO ACID TRANSAMINATION AND UREA CYCLE FUNCTION

Аннотация

This article presents a comprehensive analysis of the role of whey protein in hepatic nitrogen metabolism, with particular emphasis on amino acid transamination and the molecular and metabolic bases of the urea (ornithine) cycle. Whey protein has a high biological value; its rapid digestion and balanced amino acid composition make it an effective modulator that enhances aminotransferase activity, stimulates glutamate and glutamine synthesis, and accelerates detoxification of ammonia in the form of urea. Experimental data indicate that moderate intake of whey protein improves the energetic state of hepatocytes, optimizes amino acid metabolism, and stabilizes nitrogen balance. Keywords: whey protein, amino acid transamination, alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamate–glutamine exchange system, ammonia detoxification, urea (ornithine) cycle, CPS-I activity, stability of nitrogen balance, hepatic metabolism, protein metabolism, biologically active protein supplements. INTRODUCTION. The liver is the central organ of nitrogen metabolism in the body. It is the site where amino acid transamination, oxidative deamination, detoxification of ammonia, urea synthesis, protein biosynthesis, and multiple stages of energy metabolism take place [1,5]. Amino acid transamination is catalyzed by pyridoxal phosphate–dependent enzymes, primarily alanine aminotransferase (ALT) and aspartate aminotransferase (AST), which mediate the exchange of amino groups between amino acids and keto acids, thereby redistributing nitrogen fluxes in the organism [5,7]. Excessive accumulation of ammonia in the liver exerts a neurotoxic effect, disrupts central nervous system function, and in severe cases may lead to hepatic encephalopathy [6,9]. Therefore, rapid and efficient detoxification of ammonia via the urea cycle is one of the key conditions for maintaining homeostasis. The urea (ornithine) cycle is based on a sequence of reactions catalyzed by CPS-I, OTC, ASS, argininosuccinate lyase, and arginase, which incorporate two nitrogen atoms into one urea molecule and thus ensure excretion of nitrogen in a non-toxic form [9]. Whey protein is one of the leading dietary proteins in terms of biological value. It contains branched-chain amino acids (BCAA: leucine, isoleucine, valine), as well as glutamine, threonine, lysine, phenylalanine, and other chain amino acids in a balanced ratio [1,4]. According to A. A. Pokrovskiy and L. N. Berezovskiy, the rapid digestion and high absorption rate of whey protein allow it to be regarded as a natural substrate for transamination reactions and hepatic nitrogen metabolism [2]. 1014 ResearchBib IF - 11.01, ISSN: 3030-3753, Volume 2 Issue 11 Whey protein enhances synthesis of alanine and glutamate, activates the glucose–alanine cycle, increases glutamine formation, and promotes safe transport of ammonia from peripheral tissues to the liver [3,8]. These processes simultaneously support two key dimensions of hepatic metabolism: the molecular (enzymatic regulation) and the systemic metabolic level (influence on whole-body nitrogen balance). In this regard, the present article examines the role of whey protein in the liver in terms of: 1. its effect on aminotransferase activity and glutamate–alanine exchange; 2. its effect on the urea cycle and molecular mechanisms of ammonia detoxification. MAIN PART. Composition of whey protein and its metabolic significance Whey protein belongs to the group of complete proteins and contains almost all 20 proteinogenic amino acids, including 9 essential amino acids [1,4]. Its main fractions are β- lactoglobulin, α-lactalbumin, immunoglobulins, lactoferrin, and serum albumin, which have immunomodulatory, antioxidant, and trophic effects [4]. BCAA are predominantly oxidized in skeletal muscle; however, their transamination products return to the liver mainly in the form of alanine and glutamate [3,8]. Thus, whey protein influences hepatic metabolism in two ways: directly, by supplying free amino acids to hepatocytes; and indirectly, by activating transamination and deamination in peripheral tissues and thereby increasing alanine and glutamate flux to the liver [3,7]. 2. Role of whey protein in transamination processes Transamination reactions proceed in the presence of vitamin B6 (pyridoxal phosphate), which serves as a coenzyme for the transfer of an amino group from an amino acid to the corresponding keto acid [5,7]. ALT mainly catalyzes the alanine–pyruvate pair, whereas AST catalyzes the aspartate–oxaloacetate pair [5]. Their activity is considered an important biomarker for assessing the state of hepatic metabolic adaptation [6]. When whey protein is introduced into the diet: the content of essential amino acids increases, synthesis of alanine is significantly enhanced, the “pool” of glutamate expands, the amount of substrates entering energy metabolism (pyruvate, α-ketoglutarate) rises, and the formation of transamination pairs that transport