Ribonucleotide reductase--transition enzymes from RNA metabolism to DNA metabolism]

Ribonucleotide reductases catalyze the reduction of ribonucleotides to deoxyribonucleotides, this reaction being vitally important for all organisms. The enzyme provides a link between RNA and DNA metabolisms. Several forms of the enzyme occur in nature and those differ in their structure and catalytic mechanisms. While the direct reduction of ribonucleotides via a radical mechanism is a general mode of dNTP synthesis in all organisms, the way in which this is achieved varies. The ability of the enzyme to control DNA synthesis is of considerable clinical interest. Selective inhibition of DNA synthesis is desired, for example, in clinical applications, such as restriction of tumour growth or virus replication.     

The metabolism of taurine to isethionate

The biosynthesis of isethionate from taurine in mammalian tissue has been reexamined. In vivo metabolism of taurine to isethionate was demonstrated but it was shown that a number of acyltaurine metabolites also behave like isethionate on the conventional dual column ion-exchange chromatographic analytical system. Hydrolysis of these column effluates coupled with high-voltage electrophoresis resolves this ambiguity. In vivo formation of isethionate from taurine in mammals seems to occur from gut microorganism metabolism since: (a) germ-free mice could not convert taurine to isethionate, (b) gut anaerobes were able to metabolize taurine, (c) in vitro rat and mouse tissue failed to metabolize taurine to isethionate. These findings are in conflict with earlier reports.     

Application of macroscopic principles to microbial metabolism

General expressions for mass, elemental, energy, and entropy balances are derived and applied to microbial growth and product formation. The state of the art of the application of elemental balances to aerobic and heterotrophic growth is reviewed and extended somewhat to include the majority of the cases commonly encountered in biotechnology. The degree of reduction concept is extended to include nitrogen sources other than ammonia. The relationship between a number of accepted measures for the comparison of substrate yields is investigated. The theory is illustrated using a generalized correlation for oxygen yield data. The stoichiometry of anaerobic product formation is briefly treated, a limit to the maximum carbon conservation in product is derived, using the concept of elemental balance. In the treatment of growth energetics the correct statement of the second law of thermodynamics for growing organisms is emphasized. For aerobic heterotrophic growth the concept of thermodynamic efficiency is used to formulate a limit the substrate yield can never surpass. It is combined with a limit due to the fact that the maximum carbon conservation in biomass can obviously never surpass unity. It is shown that growth on substrates of a low degree of reduction is energy limited, for substrates of a high degree of reduction carbon limitation takes over. Based on a literature review concerning yield data some semiempirical notions useful for a preliminary evolution of aerobic heterotrophic growth are developed. The thermodynamic efficiency definition is completed by two other efficiency measures, which allow derivation of simple equations for oxygen consumption and heat production. The range of validity of the constancy of the rate of heat production to the rate of oxygen consumption is analyzed using these efficiency measures. The energetic of anaerobic growth are treated—it is shown that an approximate analysis in terms of an enthalpy balance is not valid for this case, the evaluation of the efficiency of growth has to be based on Gibbs free energy changes. A preliminary analysis shows the existence of regularities concerning the free energy conservation on anaerobic growth. The treatment is extended to include the effect of growth rate by the introduction of a linear relationship for substrate consumption. Aerobic and anaerobic growth are discussed using this relationship. A correlation useful in judging the potentialities for improvement in anaerobic product formation processes is derived. Finally the relevance of macroscopic principles to the modeling of bioengineering systems is discussed.     

Oxylipin metabolism in response to stress

Oxylipins comprise a group of biologically active compounds whose structural diversity is generated by the coordinate action of lipases, lipoxygenases, and a group of cytochromes P450 that are specialized for the metabolism of hydroperoxy fatty acids. Research on oxylipins has focused mainly on the biosynthesis of the plant signaling molecule jasmonic acid, and its role in the regulation of developmental and defense-related processes. Recent genetic studies indicate that metabolic precursors of jasmonate are active as signals in their own right, and that the synthesis and perception of jasmonates is critical for wound-induced systemic defense responses. Increasing evidence indicates that the collective biological importance of oxylipins in plants is comparable to that of the eicosanoid family of lipid mediators in animals.     

Hypoglycosylation due to dolichol metabolism defects

Dolichol phosphate is a lipid carrier embedded in the endoplasmic reticulum (ER) membrane essential for the synthesis of N-glycans, GPI-anchors and protein C- and O-mannosylation. The availability of dolichol phosphate on the cytosolic site of the ER is rate-limiting for N-glycosylation. The abundance of dolichol phosphate is influenced by its de novo synthesis and the recycling of dolichol phosphate from the luminal leaflet to the cytosolic leaflet of the ER. Enzymatic defects affecting the de novo synthesis and the recycling of dolichol phosphate result in glycosylation defects in yeast or cell culture models, and are expected to cause glycosylation disorders in humans termed congenital disorders of glycosylation (CDG). Currently only one disorder affecting the dolichol phosphate metabolism has been described. In CDG-Im, the final step of the de novo synthesis of dolichol phosphate catalyzed by the enzyme dolichol kinase is affected. The defect causes a severe phenotype with death in early infancy. The present review summarizes the biosynthesis of dolichol-phosphate and the recycling pathway with respect to possible defects of the dolichol phosphate metabolism causing glycosylation defects in humans.