Allosteric regulation enzyme kinetics

Allosterically Regulated Enzymes Do Not Follow Michaelis-Menten Kinetics... 

Fig. 2.28. The effect of substrate concentration on the catalytic reaction rate, a Enzyme obeying Michaelis-Menten kinetics b allosterically regulated enzyme with positive cooperativity c allosterically regulated enzyme with negative cooperativity...

To refer to the kinetics of allosteric inhibition as competitive or noncompetitive with substrate carries misleading mechanistic implications. We refer instead to two classes of regulated enzymes K-series and V-se-ries enzymes. For K-series allosteric enzymes, the substrate saturation kinetics are competitive in the sense that is raised without an effect on V. For V-series allosteric enzymes, the allosteric inhibitor lowers... 

Aiming at a computer-based description of cellular metabolism, we briefly summarize some characteristic rate equations associated with competitive and allosteric regulation. Starting with irreversible Michaelis Menten kinetics, the most common types of feedback inhibition are depicted in Fig. 9. Allowing all possible associations between the enzyme and the inhibitor shown in Fig. 9, the total enzyme concentration Er can be expressed as... 

The regulation of enzymes by metabolites leads to the concept of allostenc regulation. Allosteric means other structure. Allosteric modulators can bind at a site other than the active site in question and cause activation or inhibition. These modulators can include the substrate itself, which binds at another active site in a multi-subunit enzyme. In fact, allosterically modulated enzymes almost always have a complex quaternary structure (multiple subunits) and exhibit non-Michaelis-Menten kinetics. 

The red ceU enzyme is allosterically regulated by fructose-1,6-diphosphate (FDP). Sigmoid kinetics occur by increasing concentrations of the substrate phosphoenolpyruvate. 

There is some confusion in the literature about the use of the term "allosteric" for an enzyme. Many authors restrict this term to multi-subunit enzymes that show substrate cooperativity and sigmoidal kinetics. Other authors, however, are less specific and their definitions include enzymes that follow Michaelis- Menten kinetics and have non- or uncompetitive inhibitors. Fortunately, in metabolism, regulated enzymes are generally multi-subunit, cooperative, enzymes and fall into the more specific use of the term. 

Ives, D.H. Durham, J.P. Deoxycytidine kinase. 3. Kinetics and allosteric regulation of the calf thymus enzyme. J. Biol. Chem., 245, 2285-2294 (1970)... 

To clarify the role of natural and dietary compounds, an elucidation of the interaction mechanisms of these molecules with the human biological network is required, especially at a molecular level. This includes the rmcover of the biophysical mechanisms by which these compounds bind to receptors or enzymes (i.e., allosteric regulation and inhibition/activation profile) and their kinetics (i.e., reversible/irre-versible, substrate and cofactors competition/non-coiiipetition) that could underlie to specific pharmacological actions. These studies are far to be accomplished because, in many cases, it is experimentally difficult to isolate large amormts of compounds from the natural source and, even when this is possible, it is complicated to dissect their intrinsically polypharmacological roles, rendering this area of research... 

The enzyme from soybean nodules has been purified to homogeneity (Mitchell et ai, 1986). The enzyme (Af, 230,000) was composed of four apparently identical subunits. Serine was found to have a biphasic binding pattern, with limiting values of 1.5 and 40 mM. The for FH4 was 0.25 mAf. Preliminary kinetic data suggest a sequential reaction mechanism, with serine the first substrate to bind, and glycine the last product to leave. The enzyme is reported to be insensitive to a wide range of metabolites which have b reported to affect activity in other species, and no evidence was found for allosteric regulation. 

Based on kinetic studies, McKay and Shargool (1981) suggested that the reaction followed a random BiBi mechanism. The kinetic analysis was somewhat complex and the enzyme exhibited apparent negative cooperativity with iV-acetylglutamate = 1.9 mM 6.2 mM). The for ATP was 1.7 mM Arginine was an allosteric regulator of the enzyme. 

Because this enzyme catalyzes the committed step in fatty acid biosynthesis, it is carefully regulated. Palmitoyl-CoA, the final product of fatty acid biosynthesis, shifts the equilibrium toward the inactive protomers, whereas citrate, an important allosteric activator of this enzyme, shifts the equilibrium toward the active polymeric form of the enzyme. Acetyl-CoA carboxylase shows the kinetic behavior of a Monod-Wyman-Changeux V-system allosteric enzyme (Chapter 15). 

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