Fructose 1,6-bisphosphate formation

Fig. 16.7 Glycolysis showing enolase. Saccharides are processed intracellularly into UDP-sugars and metabolized to fructose 6-phosphate and then 1,6-bisphosphate if required for energy. The various steps preceding fructose 1,6-bisphosphate formation are omitted in this figure (Wikipedia public domain image slightly modified. Accessed at http //commons.wikimedia.org/wiki/ File GlycolysisPathway.svg). This figure was modified by Dr Wirsig-Weichmann...

Initial phosphorylations The formation of fructose bisphosphate occurs via two phosphorylation reactions that involve ATP hydrolysis, which are catalysed by hexokinase and phosphofructokinase ... 

As discussed in section 10.2.2, the formation of fructose bisphosphate, catalysed by phosphofructokinase, is an important step for the regulation of glucose metabolism. Once it has been formed, fructose bisphosphate is cleaved into two three-carbon compounds, which are interconvertible. The metabolism of these three-carbon sugars is linked to both the reduction of NAD" to NADH and direct (substrate-level) phosphorylation of ADP to ATP (section 3.3). The result is the formation of 2 mol of pyruvate from each mole of glucose. 

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).

The second indirect route involves the formation of fructose 6-phosphate from fructose 1,6-bisphosphate without the intervention of phosphofructokinase reaction. This route is catalyzed by fructose bisphosphatase ... 

It s unfortunate that we have to deal with PFK-1 and PFK-2. PFK-1 is the enzyme that catalyzes the formation of fructose 1,6-bisphospate from fructose 6-phosphate. PFK-2 makes the 2,6-bisphosphate. 

Lemaire et al. have developed a efficient fructose-1,6-bisphosphate aldolase (FBPA)-mediated synthesis of aminocyclitol analogs of valiolamine [34], This one-pot route involves the formation of two C—C bonds where four stereocenters are created. The first C—C bond formation reaction is catalyzed by the aldolase, coupling DHAP to nitrobutyraldehydes the other one is the result of a highly stereoselective intramolecular Henry reaction occurring on the intermediate nitroketone under acidic conditions during the aldolase-catalyzed reaction and phytase-catalyzed phosphate hydrolysis coupled step (Scheme 4.13). 

This enzyme is called PFK-1 to distinguish it from a second enzyme (PFK-2) that catalyzes the formation of fructose 2,6-bisphosphate from fructose 6-phosphate in a separate pathway. The PFK-1 reaction is essentially irreversible under cellular conditions, and it is the first committed step in the glycolytic pathway glucose 6-phosphate and fructose 6-phosphate have other possible fates, but fructose 1,6-bisphosphate is targeted for glycolysis. 

Dephosphorylated PFK-2 is active, whereas FBP-2 is inactive this favors formation of fructose 2,6-bisphosphate. 

Hydrolysis of fructose 1,6-bisphosphate by fructose 1,6-bispho -phatase bypasses the irreversible phosphofructokinase-1 reaction, and provides an energetically favorable pathway for the formation of fructose 6-phosphate (Figure 10.4). This reaction is an important regulatory site of gluconeogenesis. 

Another aspect of chloroplast metabolism is synthesis of starch. Formation of ADP-glucose from glucose 1-phosphate is induced by 3-phosphoglycerate, a "feed-ahead" type of regulation (Fig. 23-36). Although fructose 2,6-bisphosphate is absent from chloroplasts, it has an important regulatory function in the cytoplasm of plants as it does in animals.425 430 In the plant cytosol triose phosphates from the chloroplasts are converted to fructose 6-P, glucose 6-P, UDP-... 

Formation of Fructose-1,6-bisphosphate Signals a Commitment to Glycolysis... 

Fig. 2. Schematic representation of substrate binding and C-C bond formation for the class I fructose 1,6-bisphosphate aldolase from rabbit muscle...

Aldolases such as fructose-1,6-bisphosphate aldolase (FBP-aldolase), a crucial enzyme in glycolysis, catalyze the formation of carbon-carbon bonds, a critical process for the synthesis of complex biological molecules. FBP-aldolase catalyzes the reversible condensation of dihydroxyacetone phosphate (DHAP) and glyceralde-hyde-3-phosphate (G3P) to form fructose-1,6-bisphosphate. There are two classes of aldolases the first, such as the mammalian FBP-aldolase, uses an active-site lysine to form a Schiff base, whereas the second class features an active-site zinc ion to perform the same reaction. Acetoacetate decarboxylase, an example of the second class, catalyzes the decarboxylation of /3-keto acids. A lysine residue is required for good activity of the enzyme the -amine of lysine activates the substrate carbonyl group by forming a Schiff base. 

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