Ahern's BB 350 at OSU - 10. Enzymes Control I

1. Contact - [email protected] 2. Kevin's lectures with The Great Courses - https://www.thegreatcoursesplus.com/b... 3. Kevin's Lecturio videos for medical students - https://www.lecturio.com/medical-cour... 4. Course materials at https://kevingahern.com/biochemistry-... 5. Course video channel at    • Ahern's BB 350 at OSU - 1. Introduction   6. Metabolic Melodies at https://teeheetime.com/category/lyric... 7. Kevin's Free Biochemistry books - https://kevingahern.com/biochemistry-... 8. Kevin's Pre-med Audio course on Listenable - https://listenable.io/web/courses/143... One last form of enzyme inhibition we will consider is non-competitive inhibition. In non-competitive inhibition, the inhibitor does not resemble the substrate and does not compete with it for binding to the active site. It binds to a separate site on the enzyme. Because a non-competitive inhibitor does not bind to the active site, it "knocks out" a fixed percentage of the enzymes in every reaction, irrespective of the amount of substrate. Thus, Vmax of an enzyme with a non-competitive inhibitor is less than that of an uninhibited enzyme. Km, on the other hand, does not change. Highlights Enzyme Control I 1. Allosterism is only one way of controlling enzymes. ATCase is an excellent example of an allosterically controlled enzyme. It catalyzes the first step in a multi-step process. The end product of this pathway/process is CTP. CTP binds to the regulatory subunits for ATCase and inactivates the enzyme.By contrast, ATP binds to the same subunits and causes the enzyme to be activated. Activation of an enzyme results in conversion of it from the T to the R state. Inactivation of an enzyme causes the enzyme to convert from the R to the T state. Aspartate is a substrate for the enzyme that also activates it and converts the enzyme into the R state. Aspartate binds to the enzyme's catalytic subunits. 2. We have two mechanisms for explaining enzymes are activated or inactivated allosterically. They are called the sequential and the concerted models. 3. The sequential model says that binding of a molecule by an enzyme causes the change in the enzyme from R to T or from T to R. There is a cause-effect relationship between the allosteric effector (molecule affecting the enzyme) and the state of the enzyme (T or R). 4. The concerted model says that there is no cause-effect relation between the effector and the state of the enzyme. Instead, it states that the enzyme "flips" from R to T or T to R by itself and then binding of an effector LOCKS the enzyme into that state. 5. Another powerful mechanism for controlling some enzymes is covalent modification. Covalent modification involves making or breaking covalent bonds within or to an enzyme. One common covalent modification is phosphorylation (putting on a phosphate) or dephosporylation (taking off a phosphate). Only the hydroxylated aminos acids (serine, threonine, or tyrosine) are typically phosphorylated. 6. Enzymes that put phosphates onto things are called kinases. Enzymes that take phosphates off are known as phosphatases. 7. A very common type of covalent modification is phosphorylation, as exhibited by Glycogen Phosphorylase. Phosporylation converts glycogen phosphorylase b (less active) to glycogen phosphorylase a (more active). The kinase that puts the phosphates on is controlled by epinephrine (adrenalin).