Biosynthesis of nucleotides

Since only less than 10% of G-6-P is channeled into the pentose phosphate cycle (under physiological conditions this percentage varies depending on the different tissues), the question must be discussed, what is the importance of this shunt. With regard to the resulting compounds Eqs. [(3), (5), (6), (7)] one mole NADPH2 appears twice. Furthermore, pentose phosphates are furnished for biosynthesis of nucleotides, nucleic acids, and fatty acids (D5, D6, DIO, H13, M5). 

Amino Acids Amino acids that enter the liver follow several important metabolic routes (Fig. 23-14). (1) They are precursors for protein synthesis, a process discussed in Chapter 27. The liver constantly renews its own proteins, which have a relatively high turnover rate (average half-life of only a few days), and is also the site of biosynthesis of most plasma proteins. (2) Alternatively amino acids pass in the bloodstream to other organs, to be used in the synthesis of tissue proteins. (3) Other amino acids are precursors in the biosynthesis of nucleotides, hormones, and other nitrogenous compounds in the liver and other tissues. 

Kanter, U., Usadel, B., Guerineau, F., Li, Y., Pauly, M., and Tenhaken, R., 2005, The inositol oxygenase gene family of Arabidopsis is involved in the biosynthesis of nucleotide sugar precursors for cell-wall matrix polysaccharides. Planta 221 243-254. 

Eisemeich W, Schwarzkopf B, Bacher A. Biosynthesis of nucleotides, flavins, and deazaflavins in Methanobacterium ther-moautotrophicum. J. Biol. Chem. 1991 266 9622-9631. 

Chapter 25 covers the biosynthesis of nucleotides, including the role of amino acids as biosynthetic precursors. A key evolutionary insight emphasized here is that many of the enzymes in these pathways are members of the same family and catalyze analogous chemical reactions. The focus on enzymes and reactions common to these biosynthetic pathways allows students to understand the logic of the pathways, rather than having to memorize a set of seemingly unrelated reactions. 

The pathways for the biosynthesis of nucleotides fall into two classes de novo pathways and salvage pathways (Figure 25.1). In de novo (from scratch) pathways, the nucleotide bases are assembled from simpler compounds. The framework for a pyrimidine base is assembled first and then attached to ribose. In contrast, the framework for a purine base is synthesized piece by piece directly onto a ribose-based structure. These pathways comprise a small number of elementary reactions that are repeated with variation to generate different nucleotides, as might be expected for pathways that appeared very early in evolution. In salvage pathways, preformed bases are recovered and reconnected to a ribose unit. 

Figure 6.76 Pathways for the biosynthesis of nucleotide diphospho sugars of common, 6-deoxy sugars.

The ribose-5-phosphate is used for the biosynthesis of nucleotides. The erythrose-4-phosphate is used for the biosynthesis of aromatic amino acids. 

Major enzyme reactions involved in the transfer of Cl moieties and the concomitant transformations of the cognate coenzyme forms are summarized in Table 1. Whereas animals use folate-type coenzymes predominantly for the biosynthesis of nucleotides, plants and many microorganisms require them also for the biosynthesis of several essential amino acids. A detailed description of the metabolic pathways that depend on the cooperation of folate-type coenzymes is beyond the scope of the present chapter. 

Progress has also been made on the biosynthesis of nucleotide-bound 3,6-dideoxyhexoses. Thus, GDP-colitose (-3,6-dideoxy-L-xt//o-hexose) was shown to be enzymically synthesized from GDP-D-man-nose by way of GDP-6-deoxy-D-li/xo-hexos-4-ulose CDP-paratose, CDP-adequose (-3,6-dideoxy-D-xi/lo-hexose), CDP-tyvelose, and CDP- ascarylose (-3,6-dideoxy-L-arafefno-hexose) from CDP-D-glu-... 

The biosynthesis of nucleotides requires considerable expenditures of energy by organisms in long and complex pathways. Feedback inhibition at all stages plays a key role in regulating the pathway. 

Another important development was the isolation of a ribozyme which performs nncle-otide synthesis by forming a glycosidic linkage from activated ribose (pRpp) in a way similar to the modem biosynthesis of nucleotides. 

Vitamins are often required in the biosynthesis of nucleotide coenzymes (Chapt. XXII-3). 

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