Conjugation pathways

The dipyrrylacelylenedicarbaldehyde 18, which already contains, along with the acetylene moiety, two of the two-carbon bridges of the final macrotetracycle, can be prepared by a Heck-type coupling of 5-iodopyrrole-2-carbaldehydes with acetylene.8a,b The main conjugation pathway with 22n electrons is already present in the acetylene-cumulate systems 19. The expected planarity of this chromophore has been confirmed by X-ray structure analysis.8a b... 

Fig. 7. Schematic representation of possible conjugation pathways in perarylated tetra-ethynylethenes. Paths a and b depict trans- and czs-linear conjugation, respectively, and path c depicts geminal cross-conjugation. (D donor, A acceptor)...

Eyre RJ, Stevens DK, Parker JC, et al. 1995a. Acid-labile adducts to protein can be used as indicators of the cysteine trichloroethene metabolism. J Toxicol Environ Health 46 443-464. 

In general, phase I reactions, such as oxidation and ra-demethylation are delayed in the neonate but are fully operational at or above adult levels by 4-6 months of age in the full-term neonate [27a-30]. Conjugation pathways, such as glucuronidation, do not approach adult values until 3 or 4 years of age. Sulfation activity does appear to reach adult levels in early infancy. For drugs that are subject to metabolism by both pathways, such as acetaminophen, the efficient activity of the sulfation pathway allows infants and children to compensate for low glucuronidation ability... 

An alternative approach is that adopted by Horrocks and co-workers, where the aromatic residues in metal-binding proteins are used as sensitizers. Since the distance between the metal and the donor is effectively fixed, this provides a rigid scaffold for the experiment, and the absence of a directly conjugated pathway between the metals means that Forster (through space) energy transfer can be assumed. The r-6 distance-dependence of this means that the extent of sensitized emission from the lanthanide ion provides information on the spatial relationship between the metal-ion binding site (lanthanide ions often bind at Ca2+ sites) and nearby aromatic residues. 58-60... 

Although this pathway involves the formation of an AMP adduct similar to the amino acid conjugation pathway, it is really not a conjugation pathway because the result is simply the inversion of configuration. 

Although mammals all metabolize phenol to the same metabolites, the amounts of each metabolite vary between species. For example, in the old world monkeys and prosimians, sulfation is the major phenol conjugation pathway, while in the new world monkeys, glucuronidation predominates (Mehta et al. 

A. A. Elfarra, R. J. Krause, R. R. Selzer, Biochemistry of 1,3-Butadiene Metabolism and Its Relevance to 1,3-Butadiene-Induced Carcinogenicity , Toxicology 1996, 113, 23 - 30 R. A. Kemper, R. J. Krause, A. A. Elfarra, Metabolism of Butadiene Monoxide by Freshly Isolated Hepatocytes from Mice and Rats Different Partitioning between Oxidative, Hydrolytic, and Conjugations Pathways , Drug Metab. Dispos. 2001, 29, 830 - 836. 

Fig. 5.1. The ubiquitin-conjugation pathway. Steps in ubiquitin activation and substrate modification. El, ubiquitin activating enzyme E2, ubiquitin-conjugating enzyme E3, ubiquitin-protein ligase. Atoms involved in the thiol ester and amide bonds are shown.

Dharmasiri, S., Dhaemasiei, N., Hellmann, H. and Estelle, M. The RUB/Nedd8 conjugation pathway is required for early development in Arabidopsis. Embo J 2003, 22, 1762-70. 

Figure 11 The SUMO conjugation pathway. SUMO (open drop-shaped objects) is synthesized with a C-terminai extension. SUMO-specific isopeptidases (SENPs) cieave the C-terminai extension from the SUMO precursor to produce a mature protein with giycine at the C-terminai. The mature SUMO is activated by an E1 heterodimerconsistingof Uba2 and AOS1 in an ATP-dependent reaction. The action of E1 produces a SUMO-AMP intermediate (fiiied drop-shaped object), which is passed onto an E2 caiied Ubc9. E2 passes SUMO onto an E3 iigase, which attaches SUMO to the substrate. SUMO attachment is reversibie and can be removed by SENPs.

Schubert U, Anton LC, Badk I, Cox JH, Bour S, Bennink JR, Orlowski M, Strebel K, Yewdell JW (1998) CD4 glycoprotein degradation induced by human immunodeficiency virus type 1 Vpu protein requires the function of proteasomes and the ubiquitin-conjugating pathway. J Virol 72 2280-2288... 

Evidence that pentachloroaniline may enter the GSH conjugation pathway is interesting in lieu of the fact that tetrachloro-aminothioanisole was reported as a metabolite of PCNB in onion (23) and Rhesus monkey (26). 

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