Fructose-1,6-diphosphate, metabolism

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. 

P 11.91%, O 55.35%. Present in animal tissues as an equilibrium mixture with glucose-6-phosphate. The glucose-6-phosphate may be reversibly transformed into Iructose-6-phosphate by the enzyme phosphohexose isomerase. Prepn by hydrolysis of 1,6-fructose diphosphate with dil acid Neuberg, Biochem. Z. 88, 432 (1917) Ger, pat. 334,280 (Bayer) Chem. Zenfr. 1921, II, 961 Frdl. 13, 948. Role jn metabolic regulation and heat generation E. A. News-... 

Both the aldol and reverse aldol reactions are encountered in carbohydrate metabolic pathways in biochemistry (see Chapter 15). In fact, one reversible transformation can be utilized in either carbohydrate biosynthesis or carbohydrate degradation, according to a cell s particular requirement. o-Fructose 1,6-diphosphate is produced during carbohydrate biosynthesis by an aldol reaction between dihydroxyacetone phosphate, which acts as the enolate anion nucleophile, and o-glyceraldehyde 3-phosphate, which acts as the carbonyl electrophile these two starting materials are also interconvertible through keto-enol tautomerism, as seen earlier (see Section 10.1). The biosynthetic reaction may be simplihed mechanistically as a standard mixed aldol reaction, where the nature of the substrates and their mode of coupling are dictated by the enzyme. The enzyme is actually called aldolase. 

In Box 10.4 we saw that an aldol-like reaction could be used to rationalize the biochemical conversion of dihydroxyacetone phosphate (nucleophile) and glyceraldehyde 3-phosphate (electrophile) into fructose 1,6-diphosphate by the enzyme aldolase during carbohydrate biosynthesis. The reverse reaction, used in the glycolytic pathway for carbohydrate metabolism, was formulated as a reverse aldol reaction. 

One of the reactions in the metabolism of carbohydrates by the glycolytic pathway is a type of aldol addition. In this reaction D-fructose (as the 1,6-diphosphate ester) is formed from D-glyceraldehyde and 1,3-dihydroxypro-panone (both as monophosphate esters). The process is readily reversible and is catalyzed by an enzyme known as aldolase ... 

A reaction involved in the metabolism of sugars is the splitting of fructose- 1,6-diphosphate to give glyceraldehyde-3-phosphate and dihydroxyacetone phosphate. In the living system, this retro-aldol is catalyzed by an enzyme called aldolase however, it can also be catalyzed by a mild base. Propose a mechanism for the base-catalyzed reaction. 

Two metabolic patterns are discernible from the results. Carbon atoms 2, 1, and 7 of shikimate (VI) are derived almost equally from G-1,6, G-2,5, and G-3,4, respectively. In the Embden-Meyerhof pathway of hexose metabolism (see Fig. 2), D-fructose 1,6-diphosphate is cleaved to 1,3-dihydroxy-2-propanone phosphate (G-1,2,3) and D-glycerose 3-phosphate (G-4,5,6), and the two trioses are interconverted by triose phosphate isomerase. The observed randomization of label between Cl and C6, C2 and C5, and C3 and C4 of hexose therefore implies that C2, Cl, and C7 of shikimate are derived from a 3-carbon intermediate of glycolysis. The small but significant preponderance of G-6 over G-1, of G-5 over G-2, and, presumably, of G-4 over G-3, can be explained by recent observations that, in the aldolase cleavage of D-fructose 1,6-diphosphate, the 1,3-dihy-... 

Ehringer WD, Chiang B, ChienS (2001) The uptake and metabolism of fructose-1, 6-diphosphate in rat cardiomyocytes. Mol Cell Biochem 221 33—10... 

Figure 11.1 Proposed pathway for hex-ose metabolism of homofermentative LAB (1) and (2) phosphoenolpyruvate (PEP)-dependent sugar phosphotransferase system (PTS) (3) mannitol-specific PTS (4) phospho-glucose isomerase (5) mannitol-1-phosphate dehydrogenase (6) mannitol-1-phosphatase (7) 6-phosphofructokinase (8) fructose-diphosphatase (9) fructose-1,6-diphosphate aldolase (10) triosephosphate isomerase (11) glyceraldehyde-3-phosphate dehydrogenase...

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