糖酵解与糖异生作用

1.1.3.Phosphorylation of Fructose 6-Phosphate to Fructose 1,6-Bisphosphate
phosphofructokinase-1 (PFK1) catalyzes the transfer of a phosphoryl group from ATP to fructose 6-phosphate to yield fructose 1,6-bisphos-phate
1.3.2.Hexokinase set the Pace of Glycolysis
1. Hexokinase is inhibited by glucose 6-phosphate. high concentrations of this molecule signal that the cell no longer requires glucose for energy, for storage in the form of glycogen, or as a source of biosynthetic precursors, and the glucose will be left in the blood. 2. the inhibition of phosphofructokinase leads to the inhibition of hexokinase
Hexokinase
phosphofructokinase
Pyruvate kinase
Leabharlann Baidu
1.3.1.Phosphofructokinase Is the Key Enzyme in the Control of Glycolysis
1. High levels of ATP allosterically(空间异构的 ) inhibit the enzyme
by increasing its affinity for fructose 6-phosphate and diminishing the inhibitory effect of ATP . In essence, Fructose 2,6-bisphosphate is an allosteric activator that shifts the conformational equilibrium of this tetrameric enzyme from the T state to the R state.
1.2.Energy Yield in the Conversion of Glucose into Pyruvate
Canceling out common terms on both sides of the equation gives the overall equation for glycolysis under aerobic conditions:
1.1Glycolytic reaction step
1.1.1.Phosphorylation of Glucose
first step of glycolysis, glucose is activated for subsequent reactions by its phosphorylation at C-6 to yield glucose 6-phosphate,with ATP as the phosphoryl donor:
2. AMP reverses the inhibitory action of ATP, and so the activity of
the enzyme increases when the ATP/AMP ratio is lowered. In other words, glycolysis is stimulated as the energy charge falls.
in the liver ,thus lowering its affinity for fructose 6-phosphate
ATP elicits this effect by binding to a specific regulatory site that is distinct from the catalytic site.
isozymes
1.1.2.Conversion of Glucose 6-Phosphate to Fructose 6-Phosphate
The enzyme phosphohexose isomerase (phosphoglucose isomerase) catalyzes the reversible isomerization of glucose 6-phosphate, an aldose, to fructose6-phosphate, a ketose
The glycolytic pathway can be divided into three stages: （1） glucose is trapped and destabilized.（2）two interconvertible three-carbon molecules are generated by cleavage of sixcarbon fructose.（3）ATP is generated.
4. phosphofructokinase is inhibited by citrate (柠檬酸), Citrate inhibits
phosphofructokinase by enhancing the inhibitory effect of ATP.
5. Fructose 2,6-bisphosphate (F-2,6-BP) activates phosphofructokinase
announcements
1.glucose 6-phosphate cannot diffuse through the membrane, because of its negative charges 2.the addition of the phosphoryl group begins to destabilize glucose, thus facilitating its further metabolism 3.It is a irreversible reaction. 4.Hexokinase requires Mg2+ for its activity 5.induced fit 6.glucokinase (Km5~10mmol/L);Hexokinase(Km0.1mmol/L)
the energy released in the anaerobic conversion of glucose into two molecules of pyruvate is -21 kcal mol-1 (- 88 kJ mol-1)
1.3.The Glycolytic Pathway Is Tightly Controlled
1.1.4.Cleavage of Fructose 1,6-Bisphosphate
1.1.5.Interconversion of the Triose Phosphates
1.1.6.Oxidation of Glyceraldehyde 3-Phosphate to 1,3-Bisphos-phoglycerate
Thus, some ATP is salvaged from ADP, and AMP becomes the signal for the low-energy state. first, that the total adenylate pool ([ATP], [ADP], [AMP]) in a cell is constant over the short term second, the concentration of ATP > ADP> AMP. small changes in [ATP] to larger changes in [AMP] leads to tighter control by increasing the range of sensitivity of hosphofructokinase.
Biochemistry—chapter 16
Glycolysis and Gluconeogenesis
1.Glycolysis
Derived from the Greek stem glyk- , "sweet," and the word lysis, “dissolution”. a molecule of glucose is degraded in a series of enzyme-catalyzed reactions to yield two molecules of the three-carbon compound pyruvate with the concomitant net production of two molecules of ATP.
Why is AMP and not ADP the positive regulator of phosphofructokinase?
ATP is being utilized rapidly, the enzyme adenylate kinase (腺苷酸激酶)can form ATP from ADP by the following reaction:
The mechanism for this reaction
1.1.7.Phosphoryl Transfer from 1,3-Bisphosphoglycerate to ADP
1.1.8. Conversion of 3-Phosphoglycerate to 2-Phosphoglycerate
1.1.9. Dehydration of 2-Phosphoglycerate to Phosphoenolpyruvate
1.1.10.Transfer of the Phosphoryl Group from Phosphoenolpyruvate to ADP
This process is anaerobic (it does not require O2) in as much as it evolved before the accumulation of substantial amounts of oxygen in the atmosphere.Pyruvate can be further processed anaerobically (fermented) to lactate (lactic acid fermentation) or ethanol (alcoholic fermentation). Under aerobic conditions, pyruvate can be completely oxidized to CO2, generating much more ATP
In glycolysis, irreversible reactions are potential sites of control. Their activities are regulated by the reversible binding of allosteric effectors or by covalent modification.
3. A fall in pH also inhibits phosphofructokinase activity. The
inhibition of phosphofructokinase by H+ prevents excessive formation of lactic acid and a precipitous drop in blood pH (acidosis酸中毒)