Phosphoglycolate

CATALYTIC ACTIVITY D-RIBULOSE 1,5-BISPHOSPHATE +0(2) = 3-PHOSPHO-D-GLYCERATE + 2-PHOSPHOGLYCOLATE. 

The structure DAHPS from E. coli with Mn " " and the substrate analogue, 2-phosphoglycolate (PGL), in the active site has been determined. Mn " ", the most efficient metal activator of DAHPS, is coordinated by four amino acid side chains the PGL and a water molecule complete the octahedral coordination (Figure 25). " This structure is notable for the fact that it contains a rare example of a Mn—S bond in a protein. The Mn—S bond is quite long, 2.74 A, and spectroscopic evidence for the formation of this bond is lacking. " ... 

Probably the most abundant naturally occurring catalyst, this enzyme [EC 4.1.1.39], also known as rubisco , catalyzes the reaction of D-ribulose 1,5-bisphosphate with carbon dioxide to produce two 3-phospho-D-glycerate. The enzyme can also use dioxygen as a substrate instead of carbon dioxide, producing 3-phospho-D-glycerate and 2-phosphoglycolate. 

Exploitable structural differences between T.brucei(full) and human (dashed) TIM. The inhibitor 2-phosphoglycolate as observed in the structure of the human enzyme indicates the location of the active site. Drug design targets are the T.brucei AlalOO-TyrlOl, which are considerably different from their human counterpart His-Val. (From Ref.25. Copyright 1994 by Cambridge University Press.)... 

FIGURE 20-20 Oxygenase activity of rubisco. Rubisco can incorporate 02 rather than C02 into ribulose 1,5-bisphosphate. The unstable intermediate thus formed splits into 2-phosphoglycolate (recycled as described in Fig. 20-21) and 3-phosphoglycerate, which can reenter the Calvin cycle. 

The glycolate pathway converts two molecules of 2-phosphoglycolate to a molecule of serine (three carbons) and a molecule of C02 (Fig. 20-21). In the chloroplast, a phosphatase converts 2-phosphoglycolate to glycolate, which is exported to the peroxisome. There, glycolate is... 

When rubisco uses 02 rather than C02 as substrate, the 2-phosphoglycolate so formed is disposed of in an oxygen-dependent pathway. The result is increased consumption of... 

Interface between subunits A and D of phosphofructokinase near the catalytic site in (a) the T and (b) the R structures. Crystals of the enzyme in the R state were obtained in the presence of fructose-6-phosphate and ADP (see fig. 9.9) crystals in the T state were obtained in the presence of a nonphysiological allosteric inhibitor, 2-phosphoglycolate. The wavy green line represents part of the boundary between subunits A and D. The heavy green line indicates the polypeptide backbone. The side chains of Glu 161 and Arg 162 are shown in red. Note the inversion of the positions of these side chains in the two structures. (Source From T. Schirmer and P. R. Evans, Structural basis of the allosteric behaviour of phosphofructokinase, Nature 343 140, 1990.)... 

The same active site of ribulose bisphosphate carboxylase also catalyzes a competing reaction in which 02 replaces C02 as a substrate. The products of this oxygenase reaction are 3-phosphoglycerate and a two-carbon acid, 2-phosphoglycolate (fig. 15.27). Phosphoglycolate is oxidized to C02 by 02 in additional reactions involving enzymes in the cytosol, mitochondria, and another organelle, the peroxisome. This photorespiration is not coupled to oxidative phosphorylation, and it appears to constitute a severe... 

Photorespiration results from the oxygenation reaction catalyzed by ribulose bisphosphate carboxylase/ oxygenase. 2-Phosphoglycolate generated by the reaction moves from the chloroplast to the cytosol, where other enzymes break it down to C02, H20, and Pj. The oxygenation reaction, like carboxylation, does not require light directly. It occurs mainly during illumination, however, because the formation of the substrate, ribulose-1,5-bisphosphate, requires ATP and NADPH (see fig. 15.25). 

E. Lolis and G. Petsko, Biochemistry, 29, 6619 (1990). Crystallographic Analysis of the Complex Between Triose Phosphate Isomerase and 2-Phosphoglycolate at 2.5 A Resolution Implications for Catalysis. 

Rubisco is not absolutely specific for CO2 as a substrate. Molecular oxygen (O2) competes with CO2 at the active site, and about once in every three or four turnovers, rubisco catalyzes the condensation of O2 with ribulose 1,5-bisphosphate to form 3-phosphoglycerate and 2-phosphoglycolate (Fig. 20-20), a meta-bolically useless product. This is the oxygenase activity referred to in the full name of the enzyme ribulose... 

When rubisco uses O2 rather than CO2 as substrate, the 2-phosphoglycolate so formed is disposed of in an oxygen-dependent pathway. The result is increased consumption of O2—photorespiration or, more accurately, the oxidative photosynthetic carbon cycle or C2 cycle. The 2-phosphoglycolate is converted to glyoxylate, to glycine, and then to serine in a pathway that involves enzymes in the chloroplast stroma, the peroxisome, and the mitochondrion. 

Di-phosphinothridn 307 L-phosphinothricin 303, 307 phosphinothricyl alanyl-leucine 307 2-phosphoglycolate 303 phoxim 760 phthalide 973 Pico 206, 1222... 

Figure 1. Coupling of nitrite reduction to photorespiration in C3 chloroplasts. For coupled export of two bicarbonate molecules to the cytosol for each nitrite reduced, a sustained cycling process is necessary, since only one bicarbonate is formed in the first cycle (RuBP, ribulose bisphosphate 3-PGA, 3-phosphoglycerate GLYCOL, glycollate 2-PG, 2-phosphoglycollate GA, glycerate 2-OG, 2-oxoglutarate).

Triosephosphate isomerase, for example, catalyzes the interconversion of glyceraldehyde 3-phosphate and dihydroxyacetone phosphate with fccat values that vary with pH, whereas is pH independent in the neutral range. This behavior appears consistent with mechanisms in which the enzyme combines with either monoanionic or dianionic forms of the substrate with similar affinity, but only the latter forms a productive complex, ES , which goes on to form products. Unlike an ordinary substrate analog, a transition-state analog for this reaction would be expected to be bound tightly only as a dianionic species, and this appears to be the case for the inhibitor 2-phosphoglycolic acid. ... 

Phosphoglucose isomerase, 381, 382 Phosphoglycerate, 388, 390 Phosphoglycolate, 388 2-Phosphoglycolic acid, 18 2-Phosphoglycolohydroxamate, 23, 25 Phosphonomycin, 543 Phosphoribosyl pyrophosphate amido-transferase, 420, 424... 

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