Effects of quinones on free-radical processes of oxidation and fragmentation of hydroxyl-containing organic compounds

The coenzymes Q and Vitamin K(3), as well as their synthetic analogues, have been found to inhibit free-radical processes of fragmentation of hydroxyl-containing organic compounds and oxidation of the latter by molecular oxygen. It has been established that the observed effects are due to the ability of quinones to oxidize the alpha-hydroxyl-containing carbon-centered radicals formed from the starting compounds.     

The effects of ascorbic acid on homolytic processes involving alpha-hydroxyl-containing carbon-centered radicals

Effects of ascorbic acid and 5,6-O-isopropylidene-2,3-O-dimethylascorbic acid on final product formation in radiolysis of ethanol, aqueous solutions of ethanol, ethylene glycol, alpha-methylglycoside, maltose, alpha-glycerophosphate, and alpha-glucose phosphate were studied. It was found that ascorbic acid is able to suppress reactions involving various alpha-hydroxyl-containing carbon-centered radicals and depending on the experimental conditions can either oxidize or reduce alpha-hydroxyethyl radicals.     

Inhibition of muscle glycogen phosphorylase b by heterocyclic vitamins and coenzymes

Inhibition of rabbit skeletal muscle glycogen phosphorylase b by biotin, pyridoxine, lipoic acid, as well as by thiamine and cobalamine vitamins and coenzymes has been found. The values of "half-saturation" concentration and Hill coefficients are determined for biotin (27 mM, 1.3), pyridoxine (19 mM, 1.7), 5'-deoxyadenosyl-cobalamine (2.5 mM, 1.5), lipoic acid (3.4 mM, 1.1), thiamine (11 mM, 1.3), thiamine diphosphate (11 mM, 1.0). Effectiveness of the enzyme inhibition by vitamins and coenzymes containing different heterocyclic groups is analysed; riboflavin and its coenzymic forms are suggested to be the most effective inhibitors.     

The role of plant mitochondria in the biosynthesis of coenzymes

This last decade, many efforts were undertaken to understand how coenzymes, including vitamins, are synthesized in plants. Surprisingly, these metabolic pathways were often “quartered” between different compartments of the plant cell. Among these compartments, mitochondria often appear to have a key role, catalyzing one or several steps in these pathways. In the present review we will illustrate these new and important biosynthetic functions found in plant mitochondria by describing the most recent findings about the synthesis of two vitamins (folate and biotin) and one non-vitamin coenzyme (lipoate). The complexity of these metabolic routes raise intriguing questions, such as how the intermediate metabolites and the end-product coenzymes are exchanged between the various cellular territories, or what are the physiological reasons, if any, for such compartmentalization.     

Biochemical aspects of free radicals

Toxic free radicals can be produced by many reactions required for the maintenance of normal metabolism and the production of energy in the cell. The reactivity of both primary and secondary radicals with biomolecules and in whole tissue systems is of interest, not only because of their importance in radiobiology but also because of the role these species play in toxicity and various disorders. Oxidant stress is known to increase the production of free radicals. In the presence of metals, especially iron, these radicals are converted into more damaging species. Trace elements play an important role in many systems that have evolved to deal with free radicals. The dietary status of the cell can affect the preventative antioxidant constituents of the cell. The chain-breaking antioxidant status can clearly be influenced by the dietary content of substances such as vitamins E and C.     

Mitochondrial function and toxicity: role of B vitamins on the one-carbon transfer pathways

The B vitamins are water-soluble vitamins that are required as coenzymes for reactions essential for cellular function. This review focuses on the essential role of vitamins in maintaining the one-carbon transfer cycles. Folate and choline are believed to be central methyl donors required for mitochondrial protein and nucleic acid synthesis through their active forms, 5-methyltetrahydrofolate and betaine, respectively. Cobalamin (B12) may assist methyltetrahydrofolate in the synthesis of methionine, a cysteine source for glutathione biosynthesis. Pyridoxal, pyridoxine and pyridoxamine (B6) seem to be involved in the regeneration of tetrahydrofolate into the active methyl-bearing form and in glutathione biosynthesis from homocysteine. Other roles of these vitamins that are relevant to mitochondrial functions will also be discussed. However these roles for B vitamins in cell function are mostly theoretically based and still require verification at the cellular level. For instance it is still not known what B vitamins are depleted by xenobiotic toxins or which cellular targets, metabolic pathways or molecular toxic mechanisms are prevented by B vitamins. This review covers the current state of knowledge and suggests where this research field is heading so as to better understand the role vitamin Bs play in cellular function and intermediary metabolism as well as molecular, cellular and clinical consequences of vitamin deficiency. The current experimental and clinical evidence that supplementation alleviates deficiency symptoms as well as the effectiveness of vitamins as antioxidants will also be reviewed.     

Change in the ornithine carbamoyltransferase activity in rats following roentgen irradiation and administration of a vitamin-coenzyme complex

A whole-body X-irradiation (5.82 Gy) increases the activity of ornithine carbamoyl transferase (OCT) on days 3, 7, 15 and 60. After the administration of a complex of vitamins and coenzymes on days 7, 15 and 60 OCT activity decreased as compared to that of untreated animals. A correlation was noted between the activity of OCT in the liver and blood serum.     

Supplementation of the cultivation media with B-group vitamins enhances lovastatin biosynthesis by Aspergillus terreus

The impact of the supplementation of cultivation media with B-group vitamins on the biosynthesis of lovastatin (mevinolinic acid) by Aspergillus terreus ATCC20542 was investigated. A hypothesis was formulated that as the biosynthesis of lovastatin requires a high throughput of coenzymes in the cells, the application of its precursors in the form of B-group vitamins might positively influence the process. In a nitrogen-deficient medium the B-group vitamins, both single, especially nicotinamide, pyridoxine and calcium D-pantothenate, and a mixture of thiamine, riboflavin, pyridoxine, calcium d-pantothenate and nicotinamide increased the efficiency of lovastatin biosynthesis. The vitamin supplementation also increased both volumetric and specific production rates of mevinolinic acid, especially before 80 h of the process, when no lactose limitation had been observed yet.     

Mitochondrial function and toxicity: role of the B vitamin family on mitochondrial energy metabolism

The B vitamins are water-soluble vitamins required as coenzymes for enzymes essential for cell function. This review focuses on their essential role in maintaining mitochondrial function and on how mitochondria are compromised by a deficiency of any B vitamin. Thiamin (B1) is essential for the oxidative decarboxylation of the multienzyme branched-chain ketoacid dehydrogenase complexes of the citric acid cycle. Riboflavin (B2) is required for the flavoenzymes of the respiratory chain, while NADH is synthesized from niacin (B3) and is required to supply protons for oxidative phosphorylation. Pantothenic acid (B5) is required for coenzyme A formation and is also essential for alpha-ketoglutarate and pyruvate dehydrogenase complexes as well as fatty acid oxidation. Biotin (B7) is the coenzyme of decarboxylases required for gluconeogenesis and fatty acid oxidation. Pyridoxal (B6), folate and cobalamin (B12) properties are reviewed elsewhere in this issue. The experimental animal and clinical evidence that vitamin B therapy alleviates B deficiency symptoms and prevents mitochondrial toxicity is also reviewed. The effectiveness of B vitamins as antioxidants preventing oxidative stress toxicity is also reviewed.     

甲壳素及其衍生物在防病抗衰中的应用研究

甲壳素及其衍生物具有独特的生物学特性和生物保健功能,现已作为辅助药物,被广泛应用于肿瘤、糖尿病、骨关节炎和心脑血管等老年相关性疾病的治疗,也具有增强机体免疫、清除自由基、延缓机体衰老等功能.现逐渐被用作为继蛋白质、脂肪、碳水化合物、维生素和矿物质之后人体的第6生命要素.     

Radicals in Cellular Structures

Biophysics - The involvement of natural radicals in single-electron processes of cell activity is considered. It was shown that coenzymes that have intermediate free radical quinoid and semichinoid...     

Life's utilization of B vitamins on early Earth

Coenzymes are essential across all domains of life. B vitamins (B₁‐thiamin, B₂‐riboflavin, B₃‐niacin, B₅‐pantothenate, B₆‐pyridoxine, B₇‐biotin, and B₁₂‐cobalamin) represent the largest class of coenzymes, which participate in a diverse set of reactions including C₁‐rearrangements, DNA repair, electron transfer, and fatty acid synthesis. B vitamin structures range from simple to complex heterocycles, yet, despite this complexity, multiple lines of evidence exist for their ancient origins including abiotic synthesis under putative early Earth conditions and/or meteorite transport. Thus, some of these critical coenzymes likely preceded life on Earth. Some modern organisms can synthesize their own B vitamins de novo while others must either scavenge them from the environment or establish a symbiotic relationship with a B vitamin producer. B vitamin requirements are widespread in some of the most ancient metabolisms including all six carbon fixation pathways, sulfate reduction, sulfur disproportionation, methanogenesis, acetogenesis, and photosynthesis. Understanding modern metabolic B vitamin requirements is critical for understanding the evolutionary conditions of ancient metabolisms as well as the biogeochemical cycling of critical elements such as S, C, and O.     

Vitamin‐regulated cytokines and growth factors in the CNS and elsewhere

There is a growing awareness that natural vitamins (with the only exception of pantothenic acid) positively or negatively modulate the synthesis of some cytokines and growth factors in the CNS, and various mammalian cells and organs. As natural vitamins are micronutrients in the human diet, studying their effects can be considered a part of nutritional genomics or nutrigenomics. A given vitamin selectively modifies the synthesis of only a few cytokines and/or growth factors, although the same cytokine and/or growth factor may be regulated by more than one vitamin. These effects seem to be independent of the effects of vitamins as coenzymes and/or reducing agents, and seem to occur mainly at genomic and/or epigenetic level, and/or by modulating NF‐κB activity. Although most of the studies reviewed here have been based on cultured cell lines, but their findings have been confirmed by some key in vivo studies. The CNS seems to be particularly involved and is severely affected by most avitaminoses, especially in the case of vitamin B₁₂. However, the vitamin‐induced changes in cytokine and growth factor synthesis may initiate a cascade of events that can affect the function, differentiation, and morphology of the cells and/or structures not only in the CNS, but also elsewhere because most natural vitamins, cytokines, and growth factors cross the blood–brain barrier. As cytokines are essential to CNS‐immune and CNS‐hormone system communications, natural vitamins also interact with these circuits. Further studies of such vitamin‐mediated effects could lead to vitamins being used for the treatment of diseases which, although not true avitaminoses, involve an imbalance in cytokine and/or growth factor synthesis.     

代谢工程在维生素生产中的应用及研究进展

维生素是维持人体生命活动必需的一类有机物质,机体本身一般不能合成或合成量不足,因此需经食物或其他强化产品获取。目前,维生素产品已广泛应用于医药、食品添加剂、饲料添加剂、化妆品等领域,而且全球对维生素的需求也是呈逐年增长态势。维生素的生产方法主要包括化学合成法和生物合成法。化学合成法通常安全隐患大、反应条件严苛、废物污染严重,相比之下,代谢工程生产维生素绿色环保安全、能耗低,因此建立微生物细胞工厂具有重大的科学意义和应用需求。文中回顾了近30年来代谢工程在维生素生产领域的研究进展,详细阐述了水溶性维生素(维生素B1、B2、B3、B5、B6、B7、B9、B12和维生素C的前体)和脂溶性维生素(维生素A、维生素D的前体、维生素E和维生素K)的生物合成研究现状,并对其发酵生产的瓶颈进行了探讨,最后对合成生物技术创建维生素生产菌种进行了展望。     

The effect of functionally bound vitamins and their coenzyme forms on the activity of 2-oxoacid dehydrogenases in mouse organs

Ever-growing doses (beginning from the therapeutic up to 10-fold doses of a complex of five functionally bound vitamins (B1, FMN, nicotinamide, pantothenate, lipoic acid) being administered to F1 mice (CBA x Black) induced a constant and considerable rise of the pyruvate- and 2-oxoglutarate dehydrogenase (PDG and OGDG) activity in the mouse organs. In the in vitro experiments the addition of the corresponding coenzymes or their mixture (in the optimal concentrations) to the incubation medium containing mitochondria of the mouse liver led to a greater activation of these dehydrogenases in the group of animals which were preliminary injected the above complex of vitamins.     

Salivary vitamins E and C in oral cancer

Lipid peroxidation may be involved in cancer and essential nutrients that can scavenge free radicals, such as vitamins E and C, operate in concert. Levels of antioxidant vitamins E and C were estimated in 50 patients with oral cancer and 24 healthy persons served as control. Significantly lower levels of vitamins E and C were observed in oral cancer patients as compared to controls (P < 0.011). Antioxidant nutrients may be utilized to a greater extent in oral cancer patients to counteract free radical-mediated cell disturbances, resulting in a reduction in salivary antioxidant levels.     

Vitamins C and E donate single hydrogen atoms in vivo.

The antioxidant vitamins, C and E, eliminate cytotoxic free radicals by redox cycling. Energetic and kinetic considerations suggest that cycling of vitamin C and vitamin E between their reduced and free radical forms occurs via the transfer of single hydrogen atoms rather than via separate electron transfer and protonation reactions. This may enable these vitamins to reduce many of the damaging free radicals commonly encountered by biological systems while minimizing the reduction of molecular oxygen to superoxide.     

Regulation of ox liver glutamate dehydrogenase activity by coenzymes

The effects of coenzymes NAD(P) and NAD(P)H on the kinetics of the ox liver glutamate dehydrogenase reaction have been studied. The oxidized coenzymes were shown to activate alpha-ketoglutarate amination at inhibiting concentrations of NADH and NADPH. The reduced coenzymes, NADH and NADPH, inhibit glutamate deamination with both NAD and NADP as coenzymes. The data obtained are discussed in terms of literature data on the mechanisms of the coenzyme effects on the glutamate dehydrogenase activity and are inconsistent with the theory of direct ligand--ligand interactions. It was shown that the peculiarities of the glutamate dehydrogenase kinetics can easily be interpreted in the light of the two state models.     

The formation and reaction of methyl radicals produced by direct photolysis of aqueous solutions of N-acetyl substituted aliphatic amino acids at 77K.

Photolysis of amino acids, peptides and their derivatives leads to the formation of free radicals in these substances. The electron-spin-resonance spectra obtained directly after irradiation at 77 K are not very well resolved. They are recognizable as the superposition of the spectra of different types of photoproduced radicals. CH3 radicals are formed by U.V. irradiation if methyl groups are present in the molecule. These radicals are easily detectable because of their four line spectrum. In this paper the formation of methyl radicals and their reaction with undamaged molecules of N-acetyl-substituted amino acids in investigated. The number of CH3 radicals present after a 30 min U.V. irradiation is higher if preceding U.V. irradiations and heat treatments are performed. The overall concentration of radicals is reduced only partially during this heat-treatment, while the CH3 radicals decay completely. Other experiments show that the rate of and the yield of CH3 radicals by U.V. irradiation increase with the dose of a preceding gamma-irradiation. The results suggest that there are substances present which are responsible for the higher production rate of methyl radicals after a preceding treatment. It is assumed that radicals are precursors of the fast-formed CH3 radicals     

S-adenosylmethionine as an oxidant: the radical SAM superfamily

A recently discovered superfamily of enzymes function using chemically novel mechanisms, in which S-adenosylmethionine (SAM) serves as an oxidizing agent in DNA repair and the biosynthesis of vitamins, coenzymes and antibiotics. Members of this superfamily, the radical SAM enzymes, are related by the cysteine motif CxxxCxxC, which nucleates the [4Fe-4S] cluster found in each. A common thread in the novel chemistry of these proteins is the use of a strong reducing agent--a low-potential [4Fe-4S](1+) cluster--to generate a powerful oxidizing agent, the 5'-deoxyadenosyl radical, from SAM. Recent results are beginning to determine the unique biochemistry for some of the radical SAM enzymes, for example, lysine 2,3 aminomutase, pyruvate formate lyase activase and biotin synthase.