Question

Read Box 6-3 in the textbook about "Curing African Sleeping Sickness with a Biochemical Trojan Horse"

What is the enzyme that is used as a target to combat African sleeping sickness?

What is PLP and how is it involved?

List at least two types of catalysis used by the enzyme. Explain how they increase the rate of the reaction.

How does the suicide inactivator DFMO prevent the enzyme from working?

Why are the fluorine atoms particularly important in the function of DFMO?

Answer 1

Answer:

* Trypanosome alternative oxidase (a potential therapeutic target)is an enzyme that is used as target to combact African sleeping sickness.

*Pyridoxal 5′-phosphate (PLP) is the cofactor involved in the stabilization of carbanions at Cα of amino acids and plays a key role in amino acid metabolism. In each case, PLP is covalently bound to its cognate enzyme by an imine with the amino group of lysine.

Types of catalysis used by the PLP enzyme:

PLP acts as a coenzyme in all transamination reactions, and in certain decarboxylation, deamination, and racemization reactions of amino acids. The aldehyde group of PLP forms a Schiff-base linkage (internal aldimine) with the ε-amino group of a specific lysine group of the aminotransferase enzyme.

Enzyme catalysis used by the enzyme:

Enzyme catalysis is the increase in the rate of a process by a biological molecule, an "enzyme". Most enzymes are proteins, and most such processes are chemical reactions. ... The reduction of activation energy (Ea) increases the fraction of reactant molecules that can overcome this barrier and form the product.

How catalysis increase the rate of reaction:
A catalyst speeds up a chemical reaction, without being consumed by the reaction. It increases the reaction rate by lowering the activation energy for a reaction.

They do this by lowering the activation energy needed. With a catalyst, more collisions result in a reaction, so the rate of reaction increases.

suicide activator DFMO prevent the enzyme from working:

The reactive form of DFMO then reacts with either a cysteine or lysine residue in the active site to irreversibly inactivate the enzyme. Since irreversible inhibition often involves the initial formation of a non-covalent EI complex, it is sometimes possible for an inhibitor to bind to an enzyme in more than one way.

Fluorine atoms particularly important in the function of DFMO:

Polyamine biosynthetic pathway is a validated therapeutic target for large number of infectious diseases including cancer, giardiasis and African sleeping sickness, etc. α-Difluoromethylornithine (DFMO), a potent drug used for the treatment of African sleeping sickness is an irreversible inhibitor of ornithine decarboxylase (ODC), the first rate limiting enzyme of polyamine biosynthesis. The enzyme ODC of E. histolytica (EhODC) has been reported to exhibit resistance towards DFMO.