Heptulose diphosphate

Fig. 3.—The Enzymic Synthesis of D-ai(ro-Heptulose 1,7-Diphosphate from d-Fructose 1,6-Diphosphate and n-offro-Heptulose 7-Phosphate.

This enzymically prepared product was, therefore, tested with bacterial extracts. Almost quantitative conversion to shikimate took place. Furthermore, D-olcarbon atoms 4,5,6, and 7 with C, prepared from uniformly labeled D-oZiro-heptulose 7-phosphate and unlabeled n-fructose diphosphate (see Fig. 3), was converted to shikimate labeled exclusively in carbon atoms 3,4,5, and 6. It is clear, however, that a cyclization of the intact carbon-chain of D-aZtriose phosphate isomerase, carbon atoms 1,2, and 3 of the heptulose diphosphate would be derived from G-(l,6), G-(2,5), and G-(3,4), respectively. Carbon atoms 7,1, and 2 of shikimate, as discussed previously (see Fig. 1), are derived from the reverse sequence, namely, G-(3,4), G-(2,5), and G-(l,6). Apparently, carbon atoms 1,2, and 3 of the heptulose diphosphate become detached, and their order is reversed, before their incorporation into shikimic acid. 

The conversion, by bacterial extracts, of D-oZtro-heptulose 1,7-diphosphate to shikimate, essentially without side reactions, greatly facilitated subsequent study of the intermediate steps in the synthesis. It was shown that the addition of iodoacetate or fluoride completely blocks this conversion. In the presence of iodoacetate, synthesis is restored by the addition of either D-glyceronic acid 3-phosphate or enolpyruvate phosphate. In the presence of fluoride, only enolpyruvate phosphate is able to restore shikimate synthesis. Neither D-fructose 1,6-diphosphate nor pyruvate reverses these inhibitions. These results suggested that the reactions of glycolysis, from triose phosphate to enolpyruvate phosphate (see Fig. 2), are involved in the conversion of D-oZfro-heptulose diphosphate to shikimate. The effect... 

It has previously been mentioned that brief treatment of the bacterial extracts with activated carbon abolished their ability to convert D-altro-heptulose 1,7-diphosphate to 5-dehydroquinate, whereas the conversion of enolpyruvate phosphate and n-erythrose 4-phosphate to this intermediate was unaffected. However, by using larger proportions of activated carbon, for longer periods of time, extracts were produced which could still carry out the condensation between enolpyruvate phosphate and D-erythrose 4-phosphate, but could not convert 3-deoxy-D-aro5fno-heptulosonic acid... 

I, 7-diphosphate.170 1 (f> This tetrose phosphate is involved with phosphoenol pyruvate in the formation of shikimic acid via 3-deoxy-2-keto-D-ara6ino-heptonic acid 7-phosphate and, hence, of aromatic compounds.170(d) A synthesis of the tetrose phosphate has been described.170 1 Aldolase shows a high affinity for the heptulose diphosphate and, compared with that for D-fructose 1,6-diphosphate, the rate of reaction is about 60 %. The enzyme transaldolase, purified 400-fold from yeast, catalyzes the following reversible reaction by transfer of the dihydroxyacetonyl group.l70(o>... 

Mammalian FDPases will hydrolyze the next higher homolog, sedo-heptulose diphosphate, nearly as rapidly as fructose diphosphate. In other organisms, where FDPase does not hydrolyze SDP, a second enzyme specific for SDP has been found to occur. This suggests a specific metabolic function for SDPase, which remains to be elucidated. 

D-Erythrose 4-phosphate has been synthesized and shown to condense with dihydroxyacetone phosphate in the presence of aldolase to give a heptulose diphosphate with properties similar to the one described above 229 ), The synthetic tetrose phosphate is optically inactive, and is decomposed by acid at a rate similar to glyceraldehyde 3-phosphate. 

Aldolase catalyses the formation of heptulose diphosphate from a molecule of tetrose phosphate and a molecule of triose phosphate (C + C3 = C7). Phosphatase converts the heptulose-PP to heptulose-P which, with a further molecule of triose-P, in the presence of transketolase, forms a molecule of ribose-P and a molecule of ribulose-P (Q + Cj = 2Cj). The isomerase for pentose phosphates converts this mixture to ribulose-P which, in the presence of ATP and phosphopentokinase, gives ribulose-PP. 

D-afe-o-Heptulose (sedoheptulose) (XXXVII) has been synthesized from D-erythrose (XXXVIII) plus triose phosphate, using an aldolase preparation from peas.169 Aldolases from yeast and from rat liver also form heptu-lose phosphate from these substrates.7S(o) 170(a) Crystalline muscle aldolase causes the formation of L-jrZwco-heptulose (XXXVIIa) from a mixture of L-erythrose (XXXVTIIa) and hexose diphosphate.170(b)... 

In recent years the biosynthetic route for the ADP-heptose precursor of the lipopolysaccharide inner core component in the gram-negative pro-teobacterium E. coli has been elucidated.This involves isomerizion of D- erfo-heptulose-7-phosphate to D-alpha,beta-D-heptose-7-phosphate by GmhA, phosphorylation to D-alpha-D-heptose-1,7-diphosphate by HddA,... 

Heptoses, chromatography of, 287-289 from bacterial polysaccharide, 302 in bacteria, 286, 287 methylated, 288 periodate oxidation of, 288, 289 —> n-glyeero-D-galacto-, 320 —, v-glycero-D-manno-, 288, 320 —, D-glycero-L-numno-, 287, 319, 320, 326 —, h-glycero-v-manno-, 277, 278, 310, 320 Heptulose, D-altro-, 286 1,7-diphosphate, 240-248, 255 7-phosphate, 241-245, 247 —, o-manno 286 Heptulosonic acid, 3-deoxy-, 251 —, 3-deoxy-D-am5t o-, determination of, 252... 

DHAP (see Vol. 25, Chapter 7, Ref 44) with aldehydes 9, obtained by asymmetric dihydroxylation, gave after phosphatase treatment L-ftuctose (10), 6-C-plienyl-E>-g aibc/o-2-h ailose (11) or 7-deoxy-D-ga/oc/o-2-heptulose (12), Le., products with 3/ /4j/5j/(6/ )-stereochemistry, as shown in Scheme 3. The enantiomers of the three uloses were obtained by use of the hydroxylation auxiliaiy with the opposite chirality and fructose diphosphate aldolase as condensation catalyst. ... 

At first two molecules of triose phosphate combine to form hexose diphosphate fructose diphosphate), which is then hydrolyzed by a specific phosphatase to fructose 6-phosphate and phosphate. Hexose phosphate and triose phosphate interact in a transketolase reaction to produce erythrose 4-phosphate and xylulose 5-phosphate, which then rearranges to ribulose 5-phosphate (the first pentose molecule). In a type of aldol condensation, erythrose phosphate and triose phosphate combine to form sedoheptulose diphosphate (C4 - - C3 = C7), which is subsequently dephos-phorylated. The enzyme transketolase then transfers a C2 fragment from heptulose to triose phosphate yielding 2 moles of pentose xylulose 5-phosphate and ribose 5-phosphate) both must be rearranged to ribulose 5-phosphate. Having ribulose 5-phosphate available, the cycle can commence again first, phosphorylation with ATP to the diphosphate, then acceptance of CO2 by the diphosphate, and production of 2 moles of phosphoglyceric acid. 

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