Terminal catabolic reaction

In plants, the first characterized maize and barley PAOs catalyze terminal catabolic reactions (Fig. 6.1) (Federico et al. 1990, 1996 Tavladoraki et al. 1998 Radova et al. 2001 Cervelli et al. 2001,2004,2006). This type of PAO oxidizes the carbon at the endo side of the A -nitrogen of Spm and Spd, producing A-(3-aminopropyl)-4-aminobutanal and 4-aminobutanal, respectively, as well as 1,3-diaminopropane and H2O2 in both reactions (Cona et al. 2006 Angelini et al. 2010). In 2006, Tavladoraki et al. reported that plants have a back-conversion type of PAO (Fig. 6.1). They showed that Arabidopsis AtPAOl produces Spd from Spm and norspermidine from norspermine (Norspm). AtPAOl is the first plant PAO known to catalyze a PA back-conversion reaction. The current consensus indicates that plants have two types of PAOs one catalyzes a terminal catabolic reaction whereas the other catalyzes a PA back-conversion reaction. 

Fig. 6.1 Schematic drawing of the polyamines (PA) catabolic pathways in plants. Diamine Put is converted to 4-aminobutanal along with ammonia and hydrogen peroxide (H2O2) by a reaction catalyzed by CuAO. On the other hand, triamine Spd and tetraamines, Spm and T-Spm, are catabo-lized by two alternative pathways one is a terminal catabolism (TC) pathway (marked by green arrows) and the other is a back-conversion (BC) pathway (marked by red arrows). The positions of carbon oxidized by TC- and BC-type PAOs are also indicated with short green tmd red arrows, respectively...

Pig. 6.2 Main reactions catalyzed by PAOs in Arabidopsis and rice plants, a All five PAOs back-convert different PAs in Arabidopsis thaliana. b Four PAOs of seven back-convert different PAs, and two PAOs of the remaining three catabolize PAs by the terminal catabolic pathway... 

Endogenous NO is produced almost exclusively by L-arginine catabolism to L-citrul-line in a reaction catalyzed by a family of nitric oxide synthases (NOSs) [3]. In the first step, Arg is hydroxylated to an enzyme-bound intermediate "-hydroxy-1.-arginine (NHA), and 1 mol of NADPH (nicotinamide adenine dinucleotide phosphate, reduced form) and O2 are consumed. In the second step, N H A is oxidized to citrulline and NO, with consumption of 0.5 mol of NADPH and 1 mol of 02 (Scheme 1.1). Oxygen activation in both steps is carried out by the enzyme-bound heme, which derives electrons from NADPH. Mammalian NOS consists of an N-terminal oxy-... 

The preparation of trisaccharide 63 illustrates the activation and enzymic coupling of the 9-acetate of vV-acetylneuraminic acid, This involves the utilization of enzymes in a cascade of reactions which probably do not occur in cells (a) synthesis of Neu5,9Ac2 from the 6-acetate of vV-acetylmannosa-mine with the catabolic sialyl aldolase, (b) activation with CMPNeu5Ac synthetase, and (c) coupling. Acetylation in cells seems posterior to coupling. Terminal nonreducing vV-acetyl-9-O-acetylneuraminic acid residues appear... 

Cyclic AMP is catabolized to 5 -adenosine monophosphate by the enzyme cyclic nucleotide phosphodiesterase, which terminates any further cAMP-initiated reactions. This enzyme also requires Mg + for activity. Calcium, again in consort with calmodulin, can stimulate phosphodiesterase activity. Phosphodiesterase appears to exist in multiple forms, each with specificity toward different substrates. Calcium and calmodulin activate only one form of the enzyme. The enzyme is potently inhibited by methyl xanthines, such as caffeine, theophylline, and theobromine. It is believed that at least part of the pharmacological effects of such compounds can be explained through their inhibition of phosphodiesterase and the consequent reduction in the catabolism of cAMP. 

The c/s-dihydroxylation reaction catalyzed by these dioxygenases is typically highly enantioselective (often >98% ee) and, as a result, has proven particularly useful as a source of chiral synthetic intermediates (2,4). Chiral cis-dihydrodiols have been made available commercially and a practical laboratory procedure for the oxidation of chlorobenzene to IS, 2S)-3-chlorocyclohexa-3,5-diene-l,2-c diol by a mutant strain of Pseudomonas putida has been published (6). Transformation with whole cells can be achieved either by mutant strains that lack the second enzyme in the aromatic catabolic pathway, cw-dihydrodiol dehydrogenase (E.C. 1.3.1.19), or by recombinant strains expressing the cloned dioxygenase. This biocatalytic process is scalable, and has been used to synthesize polymer precursors such as 3-hydroxyphenylacetylene, an intermediate in the production of acetylene-terminated resins (7). A synthesis of polyphenylene was developed by ICI whereby ftie product of enzymatic benzene dioxygenation, c/s-cyclohexa-3,5-diene-1,2-diol, was acetylated and polymerized as shown in Scheme 2 (8). 

It has been established (Delwiche and Carson, 1953) that propionic acid bacteria are able to oxidize the intermediate products of the TCA cycle. Under anaerobic conditions the TCA cycle is also functional, and its role may not be limited to anabolic processes. In these conditions nitrate and fumarate can act as terminal electron acceptors in propionic acid bacteria. It is well known that the TCA cycle provides microorganisms with precursors for biosynthetic reactions, and plays an essential role in both the catabolic and anabolic metabolism. 

Synthetic peptide dendrimers, catalytic antibodies, RNA catalysts, peptide foldamers as well as other native or modified enzymes with completely different fxmctions were discovered to catalyze carbon-carbon bond formation [15]. 4-Oxalocrotonate tau-tomerase (4-OT) catalyzes in vivo the conversion of 2-hydroxy-2,4-hexadienedioate (136) to 2-oxo-3-hexenedioate (137) (Scheme 10.33a), and it belongs to the catabolic pathway for aromatic hydrocarbons in P. putida mt-2 [200]. This enzyme carries a catalytic amino-terminal proline, which could act as catalyst in the same fashion as the proline mediated by organocatalytic reactions. Initial studies demonstrate that this enzyme was able to catalyze aldol condensations of acetaldehyde to a variety of electrophiles 138 (Scheme 10.33b) [200]. This enzyme was also examined as a potential catalyst for carbon-carbon bond forming Michael-type reactions of acetaldehyde to nitroolefins 139 (Scheme 10.33c) [201,202]. 

The catabolism of gangliosides was also a primary concern in searching for an understanding of the alteration of ganglioside composition in tumorigenic-virus-transformed cells. The catabolism (cf. Chapter 5) of the major gangliosides Gm3 and Goia (cf. Chapter 2, Table I) is initiated by the enzymatic hydrolysis of the terminal molecule of sialic acid from the respective compounds [reactions (2) and (3)] ... 

---