Isopentenyl adenosine

J. Li, L.T. Xiao, G.M. Zeng, G.H. Huang, G.L. Shen, and R.Q. Yu, Amperometric immunosensor based on polypyrrole/poly(m-phenylenediamine) multilayer on glassy carbon electrode for cytokinin N6-(D2-isopentenyl) adenosine assay. Anal. Biochem. 321, 89—95 (2003). 

This enzyme [EC 2.5.1.27], also called 2-isopentenyl-diphosphate AMP A -isopentenyltransferase and cyto-kinin synthase, catalyzes the reaction of AMP with A -isopentenyl diphosphate to yield pyrophosphate and A -(A -isopentenyl)adenosine 5 -monophosphate. 

In fact, kinetin was not the natural cell division hormone, although as an adenine derivative it is chemically closely related to the native kinins that have been isolated from plant sources. It was D. S. Letham in New Zealand (1967) who first succeeded with a crystalline cytokinin isolated from the milky stage of immature maize (Zea mays) kernels. It was 6-substituted iso-pentenylamino purine (N6-(A2-isopentenyl)) adenosine (Figure 2d). He called the substance zeatin, and zeatin riboside was, in fact, the major active constituent of coconut milk (Letham, 1974). 

Cytokinins are unique among plant hormones in that adenine compounds of identical structure occur in nucleic acids. More specifically, particular cytokinin-active ribonucleosides occur as components of certain molecular species of tRNA. Zachau et al. (19), during the determination of the base sequences of serine tRNA in yeast, first reported an "odd" base immediately adjacent to the 3 end of the anticodon. In collaboration with Biemann et al. (20), this "odd" base was identified as the natural cytokinin isopentenyl-adenosine, which is one of the most highly active cytokinins known. 

Figure 5 Structural features of the tRNA from E. coli. Elements involved in recognition by seryl-tRNA synthetase are shaded, antideterminants against recognition by EF-Tu are hatched. The modified bases are D dihydrouridine F pseudouridine i A isopentenyl-adenosine T ribothymidine. Tertiary interactions involving base pairing are indicated by lines, those with intercalations by arrows...

Figure 9 Examples of identified thiolated nucleosides. 2-Thiocytidine (s C), 4-thiouridine (s U), 5-methyl-aminomethyl-2-thiouridine (mnm s U), and 2-methylthio-A/ -isopentenyl-adenosine (ms i A).

Essential non-steroidal isoprenoids, such as dolichol, prenylated proteins, heme A, and isopentenyl adenosine-containing tRNAs, are also synthesized by this pathway. In extrahepatic tissues, most cellular cholesterol is derived from de novo synthesis [3], whereas hepatocytes obtain most of their cholesterol via the receptor-mediated uptake of plasma lipoproteins, such as low-density lipoprotein (LDL). LDL is bound and internalized by the LDL receptor and delivered to lysosomes via the endocytic pathway, where hydrolysis of the core cholesteryl esters (CE) occurs (Chapter 20). The cholesterol that is released is transported throughout the cell. Normal mammalian cells tightly regulate cholesterol synthesis and LDL uptake to maintain cellular cholesterol levels within narrow limits and supply sufficient isoprenoids to satisfy metabolic requirements of the cell. Regulation of cholesterol biosynthetic enzymes takes place at the level of gene transcription, mRNA stability, translation, enzyme phosphorylation, and enzyme degradation. Cellular cholesterol levels are also modulated by a cycle of cholesterol esterification mediated by acyl-CoA cholesterol acyltransferase (ACAT) and hydrolysis of the CE, by cholesterol metabolism to bile acids and oxysterols, and by cholesterol efflux. 

As mentioned above, ms i A is one of the modifications observed at position 37 in tRNA molecules. Unlike yW synthesis, the formation of ms i A involves only two enzymes. In the first reaction catalyzed by MiaA, an isopentenyl group is added to the N position of adenosine, yielding the product N -isopentenyl-adenosine... 

Figure 14 Reaction catalyzed by the radical SAM enzyme MiaB in 2-methylthio-N -isopentenyl-adenosine formation (R = ribose sugar). MiaB catalyzes the thiolation and methylation of the N -isopentenyl-adenosine precursor, apparently consuming two molecules of SAM in the process. SAH, S-adenosylhomocysteine.

N -(2-Isopentenyl)adenosine, which shows strong antitumour activity, has been covalently linked to a dextran via a functionalized 2, 3 -acetal, as In (52). This attachment was expected to Increase circulatory lifetime of the drug and give Increased antitumour activity. The disulphide link In (52) was slowly... 

Hall, R.H. N (zl -isopentenyl) adenosine Chemical reactions, biosyn- thesis, metabolism and significance to the structure and function of tRNA. Prog. Nucleic Acid Res. Mol. Biol. 10, 57-86 (1970)... 

Isopentenyl adenosine Molecular weight Isopentenyl adenine Diphenylurea O-glucosyl zeatin Dihydrozeatin Zeatin... 

N - (Z -isopentenyl)adenosine (IPA) and various other N -substituted adenosines having cytokinin activity, were synthesized by condensation of 6-chloro-9-(p-D-rlbofuranosyl)purine with the appropriate amino compound. However, a better method for the synthesis of IPA or its 5 -phosphate (a "minor nucleotide" of transfer RNA) involves the alkylation of adenosine or adenylic acid with a,a"dimethylallyl bromide to give the N-1 substituted intermediate which on heating undergoes rearrangement to the N -alkylated product . A somewhat analogous,... 

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