Glycolysis fructose 6-phosphate

This reaction is followed by another phosphorylation with ATP catalyzed by the enzyme phosphofructoki-nase (phosphofructokinase-1), forming fructose 1,6-bisphosphate. The phosphofructokinase reaction may be considered to be functionally irreversible under physiologic conditions it is both inducible and subject to allosteric regulation and has a major role in regulating the rate of glycolysis. Fructose 1,6-bisphosphate is cleaved by aldolase (fructose 1,6-bisphosphate aldolase) into two triose phosphates, glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. Glyceraldehyde 3-phosphate and dihydroxyacetone phosphate are inter-converted by the enzyme phosphotriose isomerase. 

Hexose entry into glycolysis fructose, mannose, galactose-----> glucose 6-phosphate... 

F6P is a phosphorylated form of fructose commonly found in cells. F6P is an intermediate in glycolysis, gluconeogenesis, the pentose phosphate pathway, and the Calvin cycle. F6P is a substrate in biosynthesis of the important allosteric factor regulating glycolysis, fructose-2,6-bisphosphate and is also an important precursor of amino sugars (last enzyme below). 

The reaction shown is the hydrolysis of a phosphoric anhydride the phosphate acceptor is water. In the first two reactions of glycolysis, the phosphate acceptors are —OH groups of glucose and fructose, respectively, and are used to form phosphoric esters of these monosaccharides. In two reactions of glycolysis, ADP is the phosphate acceptor and is converted to ATP. 

Glucose is not the only hexose used for glycolysis— fructose, mannose, and galactose can also enter the glycolytic cycle after phosphorylation. Like glucose, fructose can be used only after phosphorylation in one of three ways [33] (1) phosphorylation to fructose-6-phosphate by hexokinase, (2) phosphorylation to fructose-6-phosphate by a specific fructokinase, and (3) phosphorylation to fructose-1-phosphate by fructokinase (Fig. 1-7). It is well established that the glu-cokinase of liver and muscle can also phosphorylate fructose. Fructose can enter muscle metabolism only in the form of fructose-6-phosphate. This is strikingly different from liver metabolism in which fructose is converted to fructose-1-phosphate by a specific fructokinase. 

This cleavage is a retro aldol reaction It is the reverse of the process by which d fruc tose 1 6 diphosphate would be formed by aldol addition of the enolate of dihydroxy acetone phosphate to d glyceraldehyde 3 phosphate The enzyme aldolase catalyzes both the aldol addition of the two components and m glycolysis the retro aldol cleavage of D fructose 1 6 diphosphate... 

Fructose-6-phosphate generated in this way enters the glycolytic pathway directly in step 3, the second priming reaction. This is the principal means for channeling fructose into glycolysis in adipose tissue, which contains high levels of fructose. 

Another simple sugar that enters glycolysis at the same point as fructose is mannose, which occurs in many glycoproteins, glycolipids, and polysaccharides (Chapter 7). Mannose is also phosphorylated from ATP by hexokinase, and the mannose-6-phosphate thus produced is converted to fructose-6-phosphate by phosphomannoisomerase. 

This enzyme interconverts ribulose-5-P and ribose-5-P via an enediol intermediate (Figure 23.30). The reaction (and mechanism) is quite similar to the phosphoglucoisomerase reaction of glycolysis, which interconverts glucose-6-P and fructose-6-P. The ribose-5-P produced in this reaction is utilized in the biosynthesis of coenzymes (including N/ DH, N/ DPH, F/ D, and Big), nucleotides, and nucleic acids (DNA and RNA). The net reaction for the first four steps of the pentose phosphate pathway is... 

N/ JDPH is considerably greater than the need for ribose-5-phosphate. The next three steps thus return some of the five-carbon units to glyceraldehyde-3-phos-phate and fructose-6-phosphate, which can enter the glycolytic pathway. The advantage of this is that the cell has met its needs for N/VDPH and ribose-5-phosphate in a single pathway, yet at the same time it can return the excess carbon metabolites to glycolysis. 

The transaldolase functions primarily to make a useful glycolytic substrate from the sedoheptulose-7-phosphate produced by the first transketolase reaction. This reaction (Figure 23.35) is quite similar to the aldolase reaction of glycolysis, involving formation of a Schiff base intermediate between the sedohep-tulose-7-phosphate and an active-site lysine residue (Figure 23.36). Elimination of the erythrose-4-phosphate product leaves an enamine of dihydroxyacetone, which remains stable at the active site (without imine hydrolysis) until the other substrate comes into position. Attack of the enamine carbanion at the carbonyl carbon of glyceraldehyde-3-phosphate is followed by hydrolysis of the Schiff base (imine) to yield the product fructose-6-phosphate. 

Figure 29.8 Mechanism of step 2 in glycolysis, the isomerization of glucose 6-phosphate to fructose 6-phosphate.

Figure 10.18 Enzymatic in situ generation of dihydroxyacetone phosphate from fructose 1,6-bisphosphate (b), with extension to an in vitro artificial metabolism for its preparation from inexpensive sugars alongthe glycolysis cascade (a), and utilization for subsequent stereoselective carbon-carbon bond formation using an aldolase with distinct stereoselectivity (c).

Glucose 6-phosphate is an important compound at the junction of several metabolic pathways (glycolysis, gluconeogenesis, the pentose phosphate pathway, glycogenosis, and glycogenolysis). In glycolysis, it is converted to fructose 6-phosphate by phosphohexose-isomerase, which involves an aldose-ketose isomerization. 

Figure 17-2. The pathway of glycolysis. ( ,—P, HOPOj " .inhibition.) At asterisk Carbon atoms 1-3 of fructose bisphosphateform dihydroxyacetone phosphate, whereas carbons 4-6 form glyceraldehyde 3-phosphate. The term "bis-," as in bisphosphate, indicates that the phosphate groups are separated, whereas diphosphate, as in adenosine diphosphate, indicates that they are joined.

The convetsion of fructose 1,6-bisphosphate to fructose 6-phosphate, to achieve a reversal of glycolysis, is catalyzed by fructose-l,6-bi pho pbatase. Its ptesence determines whether or not a tissue is capable of synthesizing glycogen not only from pymvate but also from ttiosephosphates. It is present in hvet, kidney, and skeletal muscle but is probably absent from heart and smooth muscle. 

Fructose 2,6-bisphosphate is formed by phosphorylation of fructose 6-phosphate by phosphofructoki-nase-2. The same enzyme protein is also responsible for its breakdown, since it has fructose-2,6-hisphos-phatase activity. This hifrmctional enzyme is under the allosteric control of fructose 6-phosphate, which stimulates the kinase and inhibits the phosphatase. Hence, when glucose is abundant, the concentration of fructose 2,6-bisphosphate increases, stimulating glycolysis by activating phosphofructokinase-1 and inhibiting... 

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