11: Enzymes as Drug Targets

Question 1

what is a substrate analog?

Answer 1

chemical compounds with a chemical structure that resembles the substrate molecule in an enzyme-catalyzed chemical reaction, binding to the active site (competitively)
- most common type of metabolic enzyme inhibitor

Question 2

how do statins target the metabolic pathway?

Answer 2

used to reduce cholesterol in the body
- inhibit HMG CoA reductase
- plugs up the enzyme
- substrate analog

risk: inhibit other cholesterol-related processes –> steroid hormones, vitamin D, bile acids

Question 3

what is a pharmacophore?

Answer 3

structure that all statins share to make them work

Question 4

what do bisphosphonates do?

Answer 4

bisphosphonates inhibit bone resorption
prevent resorption = more bone
- can treat osteoporosis

Question 5

what/how do bisphosphonates inhibit?

Answer 5

bisphosphonates are substrate analogs of pyrophosphate/diphosphate groups
- have similar structure/size
- have variations in the side chains
- increase enzyme affinity and distribution to bone

Question 6

why are cyclooxygenases (COX) important?

Answer 6

they are enzymes that are involved with producing inflammatory mediators (prostaglandins)

Question 7

what is the effect of inhibiting Cox-1 and Cox-2?

Answer 7

reduces prostaglandin synthesis and associated inflammation (painkiller)

Question 8

explain what prostaglandins are.

Answer 8

hormone-like fat compounds that can facilitate pain, cramping, and inflammation

Question 9

how does upstream differ from downstream in cell signaling pathways?

Answer 9

events that occur early are often called “upstream” and later events are called “downstream”

Question 10

where do many cancer mutations occur?

Answer 10

in growth factor receptor signaling pathways
- the same pathways that control normal development can become unregulated in cancer

Question 11

what is an oncogene?

Answer 11

mutated gene that has the potential to cause cancer
BAD

Question 12

what is a proto-oncogene?

Answer 12

before an oncogene is mutated, it is called a proto-oncogene.
- regulates normal cell division
GOOD

Question 13

what is the function of a tumor suppressor protein?

Answer 13

detects vastly increased cell proliferation and triggers apoptosis
- destroys rapidly dividing cells

Question 14

cancer can be induced by _____

Answer 14

1) mutation of proto-oncogene
2) loss of function of tumor suppressor

Question 15

why should kinases be targeted in cancer?

Answer 15

1) kinases can be oncogenic - mutated and can lead to cancer
2) kinases can be downstream of an oncogene - promote signaling
3) kinases can support tumor formation - required for tumor to form or grow

Question 16

what does allosteric binding mean?

Answer 16

bind to an artificial/unusual site (not the endogenous ligand binding site)