Fructose-1,6-bis-phosphate

Transfer of the phosphoryl group to ADP in step 10 then generates ATP and gives enolpyruvate, which undergoes tautomerization to pyruvate. The reaction is catalyzed by pyruvate kinase and requires that a molecule of fructose 1,6-bis-phosphate also be present, as well as 2 equivalents of Mg2+. One Mg2+ ion coordinates to ADP, and the other increases the acidity of a water molecule necessary for protonation of the enolate ion. 

The interconversion of fructose-6-phosphate and fructose-1,6 bis phosphate is a control point in glycolysis and gluconeogenesis. Gluconeogenesis is a pathway which allows carbon atoms from substrates such as lactate, glycerol and some amino acids to be used for the synthesis of glucose, so it is in effect physiologically the opposite of... 

PFK = phosphofructokinase PK = pyruvate kinase G-6-P = glucose-6-phosphate F-6-P = fructose-6-phosphate F-1,6bisP = fructose-1,6 bis phosphate... 

RAMA rabbit muscle aldolase (fructose-1,6-bis-phosphate aldolase)... 

It was reported by Horecker and coworkers that one class of aldolases (called Class I to distinguish it from the Class II aldolase that is metal ion-dependent) could be inhibited by the addition of borohydride reducing agent to reaction mixtures containing both enzyme and substrate129,130. It was then shown for the fructose- 1,6-bis-phosphate aldolase that the inhibition resulted from reduction of the Schiff base formed between the dihydroxyacetone phosphate substrate and the -amino group of a lysine side chain, thereby compromising the ability of the lysine to participate in subsequent turnover. 

The reaction of the glycolytic enzyme fructose-1,6-bis-phosphate aldolase, perhaps the best-known class I aldolase, is believed to proceed according to the mechanism shown in Scheme 12131. 

Fructose 6-phosphate is phosphorylated by ATP, forming fructose 1,6-bis-phosphate and ADP. This reaction is the first committed step in glycolysis. -Enzyme phosphofructokinase 1 (PFK1)... 

After Its formation In the chloroplast stroma, glyceraldehyde 3-phosphate Is transported to the cytosol In exchange for phosphate. The final steps of sucrose synthesis occur In the cytosol of leaf cells. In these reactions, one molecule of glyceraldehyde 3-phosphate Is Isomerized to dihydroxyacetone phosphate. This compound condenses with a second molecule of glyceraldehyde 3-phosphate to form fructose 1,6-bIs-phosphate, which Is the reverse of the aldolase reaction In glycolysis (see Figure 8-4, step 0)). Fructose 1,6-bIsphosphate Is converted primarily to sucrose by the reactions shown In the bottom portion of Figure 8-42. 

The second stage of glycolysis begins with the splitting of fructose 1,6-bis-phosphate into glyceraldehyde 3-phosphate (GAP) and dihydroxyacetone phosphate (DHAP). The products of the remaining steps in glycolysis consist of three-carbon units rather than six-carbon units. 

Cooper, S. J., Leonard, G. A., McSweeney, S. M., Thompson, A. W., Naismith, J. H., Qamar, S., Plater, A., Berry, A., and Hunter, W. N., 1996. The crystal structure of a class 11 fructose-1,6-bis-phosphate aldolase shows a novel binuclear metal-binding active site embedded in a familiar fold. Structure 4 1303-1315. 

Hereditary fructose intolerance (HFl) is caused by a low level of fructose j 1-phosphate aldolase activity in aldolase B, an isozyme of fructose 1,6-bis- phosphate aldolase that is also capable of cleaving fructose 1-phosphate. In patients of European descent, the most common defect is a single missense mutation in exon 5 (G —> C), resulting in an amino acid substitution (Ala —> Pro). As a result of this substitution, a cataly tically impaired aldolase B is synthesized in abundance. The exact prevalence of HFI in the United States is not established but is approximately 1 per 15,000 to 25,000 population. The disease is transmitted by an autosomal recessive inheritance pattern. 

D-Fructose./nritsugat levulose a ketohexose, M, 180.16, m.p. 103-105 °C (d.), [alg -135°->-92° (c = 2, water). F. tastes sweeter than any other carbohydrate and is fermentable by yeast. It crystallizes as the P-pyranose, but is present in compounds as the furanose (see Carbohydrates). Chemical reduction yields a 1 1 ratio of D-sorbitol and D-mannitol. Its me-tabolically important derivatives are fructose 1,6-bis-phosphate and the I-phosphate. 

Fig. 16.3. Model for glycolysis. Arrows in one direction indicate almost irreversible reactions. Arrows in both directions indicate reactions almost at equilibrium. Broken lines indicate activation (with encircled plus sign) or inhibition (with encircled minus sign) by metabolites. GLU is glucose, HK is hexokinase, F6P is fructose 6 phosphate, PFK is phosphofructose kinase, FDP is fructose 1,6 bi-phosphate, PEP is phosphoenolpyruvate, PK is pyruvate kinase, PYR is pyruvate, and AK is adenylate kinase and LAC is lactate. Prom [7]...

Since is positive, cycling will increase the sensitivity of the flux to regulator X provided that s j>r ,), that is, if the sensitivity of the subsequent reaction of the system to the concentration of the product, P, is greater than the sensitivity of the reverse reaction of the cycle to the concentration of P. This situation can be met in several ways (9). For example, in the fructose 6-phosphate/fructose bisphosphate cycle, fructose bisphosphatase (equivalent to C above) has aK for fructose 1,6-bis-phosphate of about 1 pM (or at least two orders of magnitude lower than many other glycolytic enzymes for their glycolytic substrates) so that it is probably saturated with fructose bisphosphate in vivo (equivalent to P in... 

Briefly, two of the five glyceraldehyde 3-phosphates are isomerized to glycerone phosphate, one of which reacts with a third glyceraldehyde 3-phosphate under the influence of fructose-bisphosphate aldolase (Section 11.2) to yield fructose 1,6-bis-phosphate which is dephosphorylated.to fructose 6-phosphate (Section 11.7). Transketolase catalyses a two-carbon unit transfer between fructose 6-phosphate and a fourth glyceraldehyde 3-phosphate to yield erythrose 4-phosphate and xylulose 5-phosphate. An aldol condensation of erythrose 4-phosphate with the second glycerone phosphate, catalyst by fructose-bisphosphate aldolase, produces sedoheptulose 1,7-bisphosphate which on dephosphorylation yields sedoheptulose 7-phos-phate. A second transketolase reaction utilizes sedoheptulose 7-phosphate and a flfth glyceraldehyde 3-phosphate to produce xylulose 5-phosphate and ribose 5-phosphate. The epimerization of both xylulose 5-phosphates and the isomerization of ribose 5-phosphate (Section 11.9) produces ribulose 5-phosphates which are phosphorylated to regenerate three ribulose 1,5-bisphosphate molecules. 

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