Phosphorylation, adenosine ribose

DNA and RNA are formed of nucleotides. Each nucleotide or nucleoside is composed of a purine or pyrimidine base linked to the 1-position of a ribose sugar in the case of RNA and a 2 -deoxyribose sugar in the case of DNA.155 The 5 position is phosphorylated in the case of a nucleotide, while the nucleoside is not phosphorylated therefore, nucleotides are nucleoside phosphates. Phosphorylation can include one, two, or three phosphate groups. The most familiar example of a phosphorylated nucleotide is phosphorylated adenosine, which occurs as the mono-, di-, and triphosphate (AMP, ADP, and ATP, respectively) and is a principal means of energy storage in biological systems. 

Figure 13.1 Chemical structures of, and relationship between, adenosine and adenosine 5 -triphosphate (ATP). Adenosine contains an adenine ring and ribose component. Phosphorylation of the latter s termial (C5) hydroxy with three phosphate groups gives ATP...

Organisms of all biological kingdoms convert 64 into the cys-teamine derivative phosphopantetheine (65) using L-cysteine as substrate. 65 is converted to coenzyme A (66) by attachment of an adenosine moiety via a pyrophosphate linker and phosphorylation of the ribose moiety. Phosphopantetheine can be attached covalently to serine residues of acyl carrier proteins that are parts of fatty acid synthases and polyketide synthases. 

Gulland and Jackson performed some experiments with 5-nucleotidase, a highly specific enzyme which dephosphorylates 5-phospho-adenosine and -inosine but not" 5-phospho-guanosine and -uridine it is apparently not yet known whether the enzyme dephosphorylates 5-phos-pho-cytidine. They found that a mixture of phosphodiesterase with 5-nucleotidase liberates 35% of the total phosphorus as inorganic phosphate, and therefore decided that two or more of the phosphoryl groups may be attached at position (5) of the ribose units. The 35% dephosphorylation, intermediate between 25 and 50%, was explained as the result of simultaneous, competitive diesterase action at A and B, on two or more phosphoryl groups ... 

Nucleoside Cyclic Pyrophosphates. Extensive work has been carried out by Matsuda et al. in their efforts to synthesise chemically stable cyclic adenosine diphosphate ribose (cADPR) analogues. The carbocyclic inosine analogue (83) was first prepared through an efficient cyclisation of an 8-bromo-A-1 -[5"-(phosphoryl)carbocyclic-ribosyl]inosine 5 -phenylthiophos-... 

The first two questions are relatively simple to answer. Adenosine, it will be remembered, is the nucleotide formed from adenine and ribose, and it can be phosphorylated to yield first adenosine monophosphate (AMP), then adenosine diphosphate (ADP) and finally ATP (see page 41). If we follow the course of its hydrolysis back to adenosine we find the following series of reactions ... 

Adenosine triphosphate, ATP, is a nucleotide composed of adenine, the sugar ribose, and a triphosphate group. The energy released by the hydrolysis of the phosphoanhydride bond between the second and third phosphoryl groups provides the energy for most cellular work. 

Adenosine differs from adenine in containing a sugar (ribose). Phosphorylation of adenosine produces a nucleotide found in RNA. 

Figure 3.8. Structures of vitamins or vitamin-derived molecules that function in oxidation-reduction reactions. The oxidation of these redox groups in the inner mitochondricil membrane contributes to the electron transport chain that carries electrons from the oxidation of glucose to oxygen and in the process pumps protons from one side to the other of the inner mitochondrial membrane (see Chapter 8 for details). The proton gradient thus formed is used to phosphorylate ADP to form 32 of the 36 ATPs resulting from the oxidation of one glucose molecule to six CO2 and six H2O molecules. A Vitamin B3, also called niacin or nicotinic acid, becomes converted to the amide (nicotinamide) and dressed up with a ribose sugar. Then, in a manner like that of riboflavin in B becomes phosphorylated to form nicotinamide mononucleotide (NMN) or further reacted with the addition of adenosine monophosphate (AMP) to form nicotinamide adenine dinucleotide (NAD). B Vitamin B2, also known as riboflavin, is shown converted to the forms involved in redox reactions such as those of the electron transport chain. (From Biochemistry, Second Edition, D. Voet and J. Voet, Copyright 1995, John Wiley Sons, New York. Reprinted with permission of John Wiley Sons, Inc.)...

Wong M, Miwa M, Sugimura T, Smulson M (1983) Relationship between histone poly (adenosine diphosphate ribosylation) and histone HI phosphorylation using anti-poly (adenosine diphosphate ribose) antibody. Biochemistry 22 2384-2389... 

The synthesis of adenosine can be conveniently divided into two parts. The first part is the synthesis of the purine system, while the second part is the attachment of the ribose to the appropriate position of the former. An interesting description of the issue of the phosphorylation (needed for the synthesis of adenosine mono-, di-, and triphosphates) is provided by Sir Alexander Todd in his lecture (December 11,1957) on the occasion of his acceptance of the Nobel Prize and, in principle, might be considered a third part of the overall synthesis problem. 

A reaction similar in type to that described above has been demonstrated in liver extracts by Wajzer and Baron for inosine-3 -phosphate synthesis from hypoxanthine and ribose-3-phosphate. The formation of the mononucleotide, adenylic acid, by the phosphorylation of adenosine by adenosinetriphosphate has also been described. The significance and integration of these different reactions remains a major problem for future effort. 

In the nucleic acids (DNA and RNA sections 9.2.1 and 9.2.2 respectively) it is the purine or pyrimidine that is important, carrying the genetic information. However, in the link between energy-yielding metabolism and the performance of physical and chemical work, what is important is the phosphorylation of the ribose. Although most reactions are linked to adenosine triphosphate, a small number are linked to guanosine triphosphate (GTP see, for example, sections 5.7 and 9-2.3-2) or uridine triphosphate (UTP section 5.5.3). 

Just as in the case of N, the source of the sulphur of higher plants is an oxidized form, namely sulphate. And just like nitrate, sulphate must first be reduced. Ultimately, sulphur is present in the doubly negative form as S. The first step in the assimilation of S is the fixation of sulphate. This is brought about by sulphate reacting with ATP to liberate pyrophosphate. An adenosine-phosphate-sulphate compound is formed and to the ribose of this compound another phosphate residue from another ATP molecule is attached. The product thus obtained is 3 -phosphoryl-5 -adenosine-phosphoryl-sulphate or simply active sulphate (Fig. 114). In this way sulphur is fixed and activated. It is this bound form of active sulphate which is subjected to reduction to the level of S. It is likely that 2 electron transitions are also implicated here. The mechanism is still unknown. 

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