Lehninger Principles Biochemistry Macmillan -Myassignmenthelp.Com

Question: Discuss About The Lehninger Principles Biochemistry Macmillan? Answer: Introduction: The term "allosteric" is derived from two Greek work, "allos" meaning "other" and "stereos" meaning "solid". Allosteric protein aids in feedback inhibition (FI). FI is defined as a process of enzyme inhibition in an ongoing biosynthetic pathway via the action of the end-product of that pathway. For example biosynthesis of D from A is catalyzed via a series of enzyme from Enz1 to Enz3. High concentration of D3 inhibits the conversion A to A. Here D is an allosteric protein that binds to the allosteric site of the enzyme (Enz1) and thereby modulating the catalytic site leading to enzyme inhibition. This kind of inhibition is known as negative allosteric inhibition and D is a negative allosteric inhibitor with no structural similarity with the A (substrate of Enz1) (Murray 2009). In this report, phosphor-fructo-kinase-1 (PFK1) will be used as an example to explain allosteric protein and enzyme inhibition mechanism. PFK-1 is the major regulatory enzyme in the biochemical process of glycolysis. It helps in the conversion of Fructose 6-phosphate to fructose 1,6-bisphosphate and uses pyrophosphate (PPi) and not ATP as the phosphate group donor (Murray 2009). The activity is PFK-1 increases whenever the ATP supply of the cell is decreased or when ATP is broken down into ADP or AMP. The action of PFK is inhibited when there is ample supply of ATP inside the cell. Thus here high concentration of ATP (final product of glycolysis) is acting as an allosteric inhibitor of PFK, inhibiting its effective binding with Fructose 6-phosphate (substrate) to produce Fructose 1,6-bisphosphate. ATP inhibits PFK-1 by binding to an allosteric site and thereby lowering the affinity of PFK-1 for Fructose 6-phosphate. On the other hand, AMP and ADP increase in concentration within the cell whenas the utilization of ATP outpaces the production. Thus, again AMP and ADP binds allosterically to relief the inhibition of PFK-1 as imposed by ATP. All these effects amalgamates to generate higher enzymatic activity when AMP and ADP accumulates and on contraty, when ATP accumulates in cell, it lowers the enzymatic activity (Murray 2009). Citrate (an ionized from of citric acid) is a major intermediate in the aerobic oxidation of fatty acids, pyruvate and amino acids and acts a key allosteric regulator of PFK-1. High concentration of citrate increases the inhibitory effect of ATP on PFK. This in turn reduces the flow of glucose through the glycolysis biochemical process. In other words, it can be said that the citrate acts as an intracellular signal that notifies the cell that it is meeting its current requirement for all the available energy-yielding metabolism via oxidation of fats and proteins (Nelson, Lehninger and Cox 2008). Fructose 2,6 bisphosphate is another allosteric effectors for PFK-1 and thus helps in maintaining hormonal regulation of glyconeogenesis and glycolysis. Fructose 2,6-bisphosphate binds to its allosteric site of PFK-1 and increases its (PFK-1) enzymatic affinity towards fructose 6-phosphate and thereby reducing the effect of allosteric inhibitor (ATP) on PFK-1. Thus Fructose 2,6-bisphosphate is positive allosteric regulator and ATP is negative allosteric regulator of PFK-1 (Murray 2009). References Murray, R.K., 2009. Harper's illustrated biochemistry (26th edition). Lange Medical Books/McGraw-Hill; Medical Publishing Division Nelson, D.L., Lehninger, A.L. and Cox, M.M., 2008.Lehninger principles of biochemistry. Macmillan