Ribonucleic enzyme

Fohc acid is a precursor of several important enzyme cofactors required for the synthesis of nucleic acids (qv) and the metaboHsm of certain amino acids. Fohc acid deficiency results in an inabiUty to produce deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and certain proteins (qv). Megaloblastic anemia is a common symptom of folate deficiency owing to rapid red blood cell turnover and the high metaboHc requirement of hematopoietic tissue. One of the clinical signs of acute folate deficiency includes a red and painhil tongue. Vitamin B 2 folate share a common metaboHc pathway, the methionine synthase reaction. Therefore a differential diagnosis is required to measure foHc acid deficiency because both foHc acid and vitamin B 2 deficiency cause... 

The nucleic acids, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), are the chemical carriers of a cell s genetic information. Coded in a cell s DNA is the information that determines the nature of the cell, controls the cell s growth and division, and directs biosynthesis of the enzymes and other proteins required for cellular functions. 

The nucleic acids DNA (deoxyribonucleic acid) and RNA (ribonucleic acid) are biological polymers that act as chemical carriers of an organism s genetic information. Enzyme-catalyzed hydrolysis of nucleic acids yields nucleotides, the monomer units from which RNA and DNA are constructed. Further enzyme-catalyzed hydrolysis of the nucleotides yields nucleosides plus phosphate. Nucleosides, in turn, consist of a purine or pyrimidine base linked to Cl of an aldopentose sugar—ribose in RNA and 2-deoxyribose in DNA. The nucleotides are joined by phosphate links between the 5 phosphate of one nucleotide and the 3 hydroxyl on the sugar of another nucleotide. 

Female NMRI mice were exposed to 100 ppm of hydrogen sulfide for 2 hours at 4-day intervals excitement was observed (Savolainen et al. 1980). Exposure also resulted in decreased cerebral ribonucleic acid (RNA), decreased orotic acid incorporation into the RNA fraction, and inhibition of cytochrome oxidase. An increase in the glial enzyme marker, 2, 3 -cyclic nucleotide-3 -phosphohydrolase, was seen. Neurochemical effects have been reported in other studies. Decreased leucine uptake and acid proteinase activity in the brain were observed in mice exposed to 100 ppm hydrogen sulfide for 2 hours (Elovaara et al. 1978). Inhibition of brain cytochrome oxidase and a decrease in orotic acid uptake were observed in mice exposed to 100 ppm hydrogen sulfide for up to 4 days (Savolainen et al. 1980). 

The second dogma had to undergo drastic correction about ten years after the correction of the first Sidney Altman from Yale University and Thomas Cech from the University of Colorado at Boulder independently discovered enzymatically active ribonucleic acids in different RNA species. This new class of RNA was called ri-bozyme (from n/wnuclease and enzyme). It was now necessary to modify the second dogma as follows ... 

The initial conversion of light into chemical energy takes place in the thylakoid membrane. Besides the chlorophylls and series of electron carriers, the thylakoid membrane also contains the enzyme adenosine triphosphate (ATP) synthase. The enzymes that are responsible for the actual fixation of C02 and the synthesis of carbohydrate reside in the stroma that surround the thylakoid membrane. The stroma also contains deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and ribosomes that are essential for protein synthesis [37]. 

In the past, dissociation of the nucleoprotein complex has been brought about by salt solutions or by heat denaturation,129 but, more recently, decomposition has been effected by hydrolysis with trypsin,126 or by the use of dodecyl sodium sulfate130 or strontium nitrate.131 Some virus nucleoproteins are decomposed by ethyl alcohol.132 This effect may be similar to that of alcohol on the ribonucleoproteins of mammalian tissues. If minced liver is denatured with alcohol, and the dried tissue powder is extracted with 10% sodium chloride, the ribonucleoproteins are decomposed to give a soluble sodium ribonucleate while the deoxyribonucleoproteins are unaffected.133 On the other hand, extraction with 10 % sodium chloride is not satisfactory unless the proteins have first been denatured with alcohol. Denaturation also serves to inactivate enzymes of the tissues which might otherwise bring about degradation of the nucleic acid during extraction. 

The position was somewhat clarified by the isolation of 2- and 3-O-phos-phonucleosides from ribonucleic acid hydrolyzates in 92 to 100% yields,134 and also by the demonstration that 5-O-phosphonucleosides are also present in enzymic digests.49, 197 Yet this information gave no indication of the nature of the alkali-labile linkages. Thus, while the majority of the experimental evidence pointed to the phosphoryl residues as being doubly esterified with adjacent nucleosides, two facts remained apparently inexplicable on the basis of this type of structure. First, ready fission by alkalis, and secondly, the absence of 5-phosphates from alkaline hydrolyzates and their presence in enzymic digests. Both these facts have been explained by Brown and Todd in the following way.92... 

Hydrolysis of ribonucleic acids by snake venom was found to yield inorganic phosphate, nucleosides, and pyrimidine ribonucleoside diphosphates.197 These diphosphates were shown by their behavior toward various enzymes to be mixtures of 2,5- and 3,5-diphosphates, and it therefore seems likely that they were formed through intermediate, cyclic phosphates. Thus, although this evidence confirms the existence of 2(or 3) — 5 linkages, it does not distinguish between the 2- and 3-positions. 

Enzymes are biological catalysts—i. e substances of biological origin that accelerate chemical reactions (see p. 24). The orderly course of metabolic processes is only possible because each cell is equipped with its own genetically determined set of enzymes. It is only this that allows coordinated sequences of reactions (metabolic pathways see p. 112). Enzymes are also involved in many regulatory mechanisms that allow the metabolism to adapt to changing conditions (see p.ll4). Almost all enzymes are proteins. However, there are also catalytically active ribonucleic acids, the ribozymes" (see pp. 246, 252). 

The following reviews describe the molecular and physical properties of this broad class of enzymes that catalyze the endohydrolysis of deoxyribonucleic acids and ribonucleic acids. The class includes deoxyribonuclease II [EC 3.1.22.1], Aspergillus deoxyribonuclease Ki [EC 3.1.22.2], deoxyribonuclease V [EC 3.1.22.3], crossover junction endoribonuclease [EC 3.1.22.4], and deoxyribonuclease X [EC 3.1.22.5]. See also Deoxyribonucleases Restriction Enzymes Ribonucleases... 

Atomic oxygen attacks and destroys enzymes and other protein molecules, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) molecules, and other essential biochemical molecules, interrupting... 

The pH-rate profile for the action of the enzyme shows a typical pH maximum, with sharply lower rates at either higher or lower pH than the optimum these facts suggest that both an acidic and a basic group are required for activity (Herries, 1960). The two essential histidine residues could serve as these groups if, in the active site, one were protonated and the other present in its basic form. The simultaneous acid-base catalysis would parallel that of the model system (discussed below) of Swain and J. F. Brown. The essential lysine, which binds phosphate, presumably serves to bind a phosphate residue of the ribonucleic acid. These facts led Mathias and coworkers to propose the mechanism for the action of ribonuclease that is shown in (13) (Findlay et al., 1961). 

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