Biochemistry (Moscow) (v.80, #9)

Hyaluronic acid is an evolutionarily ancient molecule commonly found in vertebrate tissues and capsules of some bacteria. Here we review modern data regarding structure, properties, and biological functions of hyaluronic acid in mammals and Streptococcus spp. bacteria. Various aspects of biogenesis and degradation of hyaluronic acid are discussed, biosynthesis and degradation metabolic pathways for glycosaminoglycan together with involved enzymes are described, and vertebrate and bacterial hyaluronan synthase genes are characterized. Special attention is given to the mechanisms underlying the biological action of hyaluronic acid as well as the interaction between polysaccharide and various proteins. In addition, all known signaling pathways involving hyaluronic acid are outlined. Impaired hyaluronic acid metabolism, changes in biopolymer molecular weight, hyaluronidase activity, and enzyme isoforms often accompany carcinogenesis. The interaction between cells and hyaluronic acid from extracellular matrix that may be important during malignant change is discussed. An expected role for high molecular weight hyaluronic acid in resistance of naked mole rat to oncologic diseases and the protective role of hyaluronic acid in bacteria are discussed.
Keywords: hyaluronic acid; hyaluronan synthase; hyaluronidase; hyaladherins; naked mole rat; Streptococcus spp. bacteria

Chitin and products of its hydrolysis in Vibrio cholerae ecology by E. Yu. Markov; E. S. Kulikalova; L. Ya. Urbanovich; V. S. Vishnyakov; S. V. Balakhonov (1109-1116).
The role of chitin and its hydrolysis products generated by Vibrio cholerae chitinases in mechanisms of its adaptation in water environments, metabolism, preservation, acquisition of pathogenic potential, and its epidemiological value are reviewed. Chitin utilization by V. cholerae as a source of energy, carbon, and nitrogen is described. Chitin association promotes biofilm formation on natural chitinous surfaces, increasing V. cholerae resistance to adverse factors in ecological niches: the human body and water environments with its inhabitants. Hydrolytic enzymes regulated by the corresponding genes result in complete chitin biodegradation by a chitinolytic catabolic cascade. Consequences of V. cholerae cell and chitin interaction at different hierarchical levels include metabolic and physiological cell reactions such as chemotaxis, cell division, biofilm formation, induction of genetic competence, and commensalic and symbiotic mutual relations with higher organisms, nutrient cycle, pathogenicity for humans, and water organisms that is an example of successful interrelation of bacteria and substratum in the ecology of the microorganism.
Keywords: Vibrio cholerae eltor ; chitinolytic cascade; genetic regulation; ecology

Circulating microRNAs by J. A. Makarova; M. U. Shkurnikov; A. A. Turchinovich; A. G. Tonevitsky; A. I. Grigoriev (1117-1126).
The detection of miRNAs in plasma and other body fluids opened up a fascinating possibility that animal noncoding RNAs can act as extracellular signaling molecules. In this review, we discuss recent progress in the field including the ability of miRNAs to participate in intercellular communication in vitro and in vivo, and the application of circulating miRNAs as diagnostic markers of a wide range of diseases. Special attention is paid to the relevance of the development and unification of current techniques for isolation of circulating miRNAs.
Keywords: miRNA; exosomes; biomarkers; noncoding RNA; cancer

Amyloids: from pathogenesis to function by A. A. Nizhnikov; K. S. Antonets; S. G. Inge-Vechtomov (1127-1144).
The term “amyloids” refers to fibrillar protein aggregates with cross-ß structure. They have been a subject of intense scrutiny since the middle of the previous century. First, this interest is due to association of amyloids with dozens of incurable human diseases called amyloidoses, which affect hundreds of millions of people. However, during the last decade the paradigm of amyloids as pathogens has changed due to an increase in understanding of their role as a specific variant of quaternary protein structure essential for the living cell. Thus, functional amyloids are found in all domains of the living world, and they fulfill a variety of roles ranging from biofilm formation in bacteria to long-term memory regulation in higher eukaryotes. Prions, which are proteins capable of existing under the same conditions in two or more conformations at least one of which having infective properties, also typically have amyloid features. There are weighty reasons to believe that the currently known amyloids are only a minority of their real number. This review provides a retrospective analysis of stages in the development of amyloid biology that during the last decade resulted, on one hand, in reinterpretation of the biological role of amyloids, and on the other hand, in the development of systems biology of amyloids, or amyloidomics.
Keywords: amyloid; prion; protein; ß-sheet; yeast; amyloidomics; amyloidosis

Adaptive epibiochemistry and epigenetics by Ya. I. Buryanov (1145-1156).
Enzymatic reactions of post-synthetic modification of macromolecules occur in the cells of all organisms. These reactions, which can be designated as epibiochemical, are of a special type and, as discriminated from reactions with low molecular weight substrates, occur on the level of biopolymers, causing their covalent modification. The majority of epibiochemical modifications of proteins, DNA, and RNA are reversible and are carried out by modification transferases and demodification enzymes, respectively. Epibiochemical, i.e. those located above the low molecular weight metabolites, modifications of proteins and nucleic acids perform various functions, including participation in molecular mechanisms of adaptive epigenetic heredity. This paper presents an overview of some adaptive epibiochemical modifications of macromolecules and the adaptive epigenetic processes on their basis. The features of epigenetic inheritance of acquired characteristics and the limits of biological evolution are discussed.
Keywords: adaptation; epibiochemistry; epigenetics; transgenerational heredity; evolution

Activity of redox enzymes in the thallus of Anthoceros natalensis by A. V. Chasov; R. P. Beckett; F. V. Minibayeva (1157-1168).
Anthocerotophyta (hornworts) belong to a group of ancient nonvascular plants and originate from a common ancestor with contemporary vascular plants. Hornworts represent a unique model for investigating mechanisms of formation of stress resistance in higher plants due to their high tolerance to the action of adverse environmental factors. In this work, we demonstrate that the thallus of Anthoceros natalensis exhibits high redox activity changing under stress. Dehydration of the thallus is accompanied by the decrease in activities of intracellular peroxidases, DOPA-peroxidases, and tyrosinases, while catalase activity increases. Subsequent rehydration results in the increase in peroxidase and catalase activities. Kinetic features of peroxidases and tyrosinases were characterized as well as the peroxidase isoenzyme composition of different fractions of the hornwort cell wall proteins. It was shown that the hornwort peroxidases are functionally similar to peroxidases of higher vascular plants including their ability to form superoxide anion-radical. The biochemical mechanism was elucidated, supporting the possible participation of peroxidases in the formation of reactive oxygen species (ROS) via substrate—substrate interactions in the hornwort thallus. It has been suggested that the ROS formation by peroxidases is an evolutionarily ancient process that emerged as a protective mechanism for enhancing adaptive responses of higher land plants and their adaptation to changing environmental conditions and successful colonization of various ecological niches.
Keywords: hornwort; peroxidase; superoxide; catalase; tyrosinases; dehydration; rehydration

The effect of carotenoids on the assembly of LH2 complex in cells of the purple nonsulfur bacterium Rhodoblastus acidophilus was investigated. For this purpose, the bacterial culture was cultivated with an inhibitor of carotenoid biosynthesis — 71 µM diphenylamine (DPA). The inhibitor decreased the level of biosynthesis of the colored carotenoids in membranes by ~58%. It was found that a large amount of phytoene was accumulated in them. This carotenoid precursor was bound nonspecifically to LH2 complex and did not stabilize its structure. Thermostability testing of the isolated LH2 complex together with analysis of carotenoid composition revealed that the population of this complex was heterogeneous with respect to carotenoid composition. One fraction of the LH2 complex with carotenoid content around 90% remains stable and was not destroyed under heating for 15 min at 50°C. The other fraction of LH2 complex containing on average less than one molecule of carotenoid per complex was destroyed under heating, forming a zone of free pigments (and polypeptides). The data suggest that a certain part of the LH2 complexes is assembled without carotenoids in cells of the nonsulfur bacterium Rbl. acidophilus grown with DPA. These data contradict the fact that the LH2 complex from nonsulfur bacteria cannot be assembled without carotenoids, but on the other hand, they are in good agreement with the results demonstrated in our earlier studies of the sulfur bacteria Allochromatium minutissimum and Ectothiorhodospira haloalkaliphila. Carotenoidless LH2 complex was obtained from these bacteria with the use of DPA (Moskalenko, A. A., and Makhneva, Z. K. (2012) J. Photochem. Photobiol., 108, 1–7; Ashikhmin, A., et al. (2014) Photosynth. Res., 119, 291–303).
Keywords: photosynthetic bacteria; photosynthesis; LH2 complex; assembly; carotenoid; inhibitor

Low concentrations of hydrogen peroxide activate the antioxidant defense system in human sperm cells by V. V. Evdokimov; K. V. Barinova; V. B. Turovetskii; V. I. Muronetz; E. V. Schmalhausen (1178-1185).
The effect of low concentrations of hydrogen peroxide (10–100 µM) on sperm motility and on the activity of the sperm enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDS) was investigated. Incubation of semen samples with 10 and 100 µM hydrogen peroxide increased the content of spermatozoa with progressive motility by 20 and 18%, respectively, and enhanced the activity of GAPDS in the sperm cells by 27 and 20% compared to a semen sample incubated without additions. It was also found that incubation with 10 µM hydrogen peroxide increased the content of reduced glutathione (GSH) in sperm cells by 50% on average compared to that in the control samples. It is supposed that low concentrations of hydrogen peroxide activate the pentose phosphate pathway, resulting in NADPH synthesis and the reduction of the oxidized glutathione by glutathione reductase yielding GSH. The formed GSH reduces the oxidized cysteine residues of the GAPDS active site, increasing the activity of the enzyme, which in turn enhances the content of sperm cells with progressive motility. Thus, the increase in motile spermatozoa in the presence of low concentrations of hydrogen peroxide can serve as an indicator of normal functioning of the antioxidant defense system in sperm cells.
Keywords: glyceraldehyde-3-phosphate dehydrogenase; spermatozoa; reactive oxygen species; antioxidant defense

Four components of the conjugated redox system in organisms: Carbon, nitrogen, sulfur, oxygen by E. V. Tereshina; V. N. Laskavy; S. I. Ivanenko (1186-1200).
C1 compounds participate in various metabolic processes and regulations including DNA methylation. Formaldehyde (FA), a product of methyl group oxidation, is highly cytotoxic. In the cell, there are two pathways of its utilization: assimilation and oxidation. Formaldehyde displays cytotoxicity, and therefore its oxidation is considered as detoxification. The sensitivity to the threshold concentration of FA we regard as an indication of its major role in biosystem functioning. A model of a three-component conjugated redox system is proposed in which the methyl group oxidation pathway is an archaic and conservative donor of protons and electrons, the reduction of O2 serves as an acceptor, and the arginine amino group is used for production of both urea and nitric oxide (the donor and acceptor, respectively). The fourth component of the redox system is glutathione, which maintains redox balance. The three-level system of proton donors includes the oxidation of a methyl group (first level), the oxidation of acetate in mitochondria (second level), and glucose catabolism in the pentose phosphate pathway (third level). The whole redox system is united by the sulfhydryl groups of cysteines, glutathione, thioredoxin, and α-lipoic acid. The central regulatory role in this redox system belongs to glutathione-dependent formaldehyde dehydrogenase, which controls FA binding with tetrahydrofolic acid, arginine methylation, and denitrosation of sulfhydryl groups. The conjugated redox system was formed during evolution as a union of separate redox cycles of carbon, nitrogen, sulfur, and oxygen.
Keywords: redox system; formaldehyde; arginine; hydrogen peroxide; sulfhydryl groups; regulation