an enzyme inhibitor

these can be other molecules or ions and they are important in the regulation of cellular activity.

many common drugs and toxins are enzyme inhibitors

inhibitors can be used to investigate enzyme mechanisms

list the 2 types of enzyme inhibitors

list the 3 subtypes of inhibitors

Irreversible & Reversible

Competitive: bind active site

Non-competitive: bind not at active site

Uncompetitive: bind the ES complex

these are molecules that have a similar shape to the substrate. they can bind the active site but cannot be metabolised by enzymes.

However, most inhibitors are not substrate analogues but transition state analogues

describe irreversible inhibition

what kind of bonding does it involve?

this is when the inhibitor binds permanently to the enzyme through covalent bonding or very high affinity non-covalent binding

they react usually with the active site of the enzyme completely inactivating it and are usually toxic to cells as they stop the fucntioning of the enzyme they have bound to.

aspirin is a non steroidal anti inflammatory drug (NSAID) and an example of which type of inhibitor?

when was aspirin first marketed?

how does aspirin work?

aspirin is an example of an irreversible inhibitor.

it was first marketed in 1899

it works by blocking Prostoglandin synthesis

which two plants was aspirin originally extracted from?

what is aspirin's posh name?

Salix alba - white willow

Spiraea ulmaria - meadowsweet

aspirin = acetylysalicyclic acid or acetylsalicyclate

which response is prostaglandin synthesis involved in?

which enzyme is involved in prostaglandin synthesis?

prostaglandins are involved in the inflammotary response

Prostaglandin H2 synthase is involved in prostaglandin synthesis. It is also known as cyclooxygenase

how mnay major isoforms of cyclooxygenase are there?

Name these

2 major isoforms

COX 1 & COX 2

COX 1 is widespread and constitutive

COX 2 is released during inflammatory response

true or false?

structurally related molecules also function as COX inhibitors?

True

eg acetaminophen (paracetamol) Ibuprofen and Naproxen are all structurraly similar to acetylsalicyclic acid (aspirin)

Low dose - to prevent throbosis

this inhibits COX1 in blood platelets, preventing prostaglandin/thromboxane-mediated aggregation

methotrexate is a chemotherapy drug and is an example of which type of inhibitor?

which key enzyme in folate metabolism became the first target for chemotherapy drugs?

it is type of a competitive inhibitor

Dihydrofolate reductase (DHFR) became the first target for chemotherapy drugs.

Aminopterin

a few years later methotrexate was produced. it bound more tightly and had better clinical effects

it blocks nucleoside base synthesis and prevents DNA replication. it prevents cell division by inhibiting DNA replication

Methotrexate is a major chemotherapy drug for treatment of cancers of the breast, bladder, head and neck

it is an antimalarial DHFR inhibitor that targets DHFR enzyme in mosquitos not humans.

DHFR stands for Dihydrofolate reductase

5-Fluorouracil

this blocks DNA synthesis by inhibiting the production of pyramidines and purines

it has similar applications to methotexate and MTX and 5-FU are often used in combination

which type of inhibitor can bind either the enzyme or the enzyme substrate complex? 

Hint: this type of inhibitor binds at a site away from the active site

Non- competitve inhibitor. These do not change Km but affect the rate of catalysis ie. turnover number

as these do not affect substrate binding, they cannot be over come by addition of more substrate

non-competitive inhibition is rare in nature as most inhibitors that act away form the active site tend to be irreversible inhibitors.

the over all affect on kinetics is similar to irreversible inhibition

the Enzyme-Substrate complex but not free enzyme

an example is Lithium as drug treatment for manic depression. It is an inhibitor of myo-inositol monophosphatase