Understanding D-Ribose and Mitochondrial Function

Mitochondria are important organelles referred to as cellular powerhouses for their unique properties of cellular energy production. With many pathologic conditions and aging, mitochondrial function declines, and there is a reduction in the production of adenosine triphosphate. The energy carrying molecule generated by cellular respiration and by pentose phosphate pathway, an alternative pathway of glucose metabolism. D-ribose is a naturally occurring monosaccharide found in the cells and particularly in the mitochondria is essential in energy production. Without sufficient energy, cells cannot maintain integrity and function. Supplemental D-ribose has been shown to improve cellular processes when there is mitochondrial dysfunction. When individuals take supplemental D-ribose, it can bypass part of the pentose pathway to produce D-ribose-5-phosphate for the production of energy. In this article, we review how energy is produced by cellular respiration, the pentose pathway, and the use of supplemental D-ribose.

L-Arabitol Is the Actual Inducer of Xylanase Expression in Hypocrea jecorina (Trichoderma reesei)

ABSTRACTThe saprophytic fungusHypocrea jecorina(anamorph,Trichoderma reesei) is an important native producer of hydrolytic enzymes, including xylanases. Regarding principles of sustainability, cheap and renewable raw materials, such asd-xylose (the backbone monomer of xylan), have been receiving increasing attention from industries. Recently, it was demonstrated that small (0.5 to 1 mM) amounts ofd-xylose induce the highest expression of xylanase inH. jecorina. However, it was also reported that active metabolism ofd-xylose is necessary for induction. In this report, we demonstrate that xylitol, the next intermediate in the pentose pathway afterd-xylose, does not trigger transcription of xylanase-encoding genes inH. jecorinaQM9414. The highest level of transcription of xylanolytic enzyme-encoding genes occurred in anxdh1(encoding a xylitol dehydrogenase) deletion strain cultured in the presence of 0.5 mMd-xylose, suggesting that a metabolite upstream of xylitol is the inducer. The expression levels of xylanases in anxdh1-lad1double-deletion strain were lower than that of anxdh1deletion strain. This observation suggested thatl-xylulose is not an inducer and led to the hypothesis thatl-arabitol is the actual inducer of xylanase expression. A direct comparison of transcript levels following the incubation of theH. jecorinaparental strain with various metabolites of the pentose pathway confirmed this hypothesis. In addition, we demonstrate thatxyr1, the activator gene, is not induced in the presence of pentose sugars and polyols, regardless of the concentration used; instead, we observed low constitutive expression ofxyr1.

Characterization of Escherichia coliD-arabinose 5-phosphate isomerase encoded by kpsF: implications for group 2 capsule biosynthesis

In Escherichia coli, there are multiple paralogous copies of the enzyme API [A5P (D-arabinose 5-phosphate) isomerase], which catalyses the conversion of the pentose pathway intermediate Ru5P (D-ribulose 5-phosphate) into A5P. A5P is a precursor of Kdo (3-deoxy-D-manno-octulosonate), an integral carbohydrate component of various glycolipids coating the surface of the OM (outer membrane) of Gram-negative bacteria, including LPS (lipopolysaccharide) and many group 2 K-antigen capsules. The K-antigen-specific API KpsF has been cloned from the uropathogenic E. coli strain CFT073 and its biochemical properties characterized. Purified recombinant KpsF [K-API (K-antigen API)] is tetrameric and has optimal activity at pH 7.8. The enzyme is specific for A5P and Ru5P, with Km (app) values of 0.57 mM for A5P and 0.3 mM for Ru5P. The apparent kcat in the A5P to Ru5P direction is 15 and 19 s−1 in the Ru5P to A5P direction. While most of the properties are quite similar to its LPS API counterpart KdsD, the catalytic constant is nearly 10-fold lower. K-API is now the second Kdo biosynthetic related gene that has been characterized from the kps group 2 capsule cluster.

Glutathione and K+ channel remodeling in postinfarction rat heart

Electrical remodeling of the diseased ventricle is characterized by downregulation of K+ channels that control action potential repolarization. Recent studies suggest that this shift in electrophysiological phenotype involves oxidative stress and changes in intracellular glutathione (GSH), a key regulator of redox-sensitive cell functions. This study examined the role of GSH in regulating K+ currents in ventricular myocytes from rat hearts 8 wk after myocardial infarction (MI). Colorimetric analysis of tissue extracts showed that endogenous GSH levels were significantly less in post-MI hearts compared with controls, which is indicative of oxidative stress. This change in GSH status correlated with significant decreases in activities of glutathione reductase and γ-glutamylcysteine synthetase. Voltage-clamp studies of isolated myocytes from post-MI hearts demonstrated that downregulation of the transient outward K+ current ( I to) could be reversed by pretreatment with exogenous GSH or N-acetylcysteine, a precursor of GSH. Upregulation of I to was also elicited by dichloroacetate, which increases glycolytic flux through the GSH-related pentose pathway. This metabolic effect was blocked by inhibitors of glutathione reductase and the pentose pathway. These data indicate that oxidative stress-induced alteration in the GSH redox state plays an important role in I to channel remodeling and that GSH homeostasis is influenced by pathways of glucose metabolism.