Biochemistry Quiz 7

Question 1

What does Gq signal through?

Answer 1

Phospholipase C-B (Effector)
-cleaves PIP2 (hydrolyzes it) to produce 2nd messengers

Question 2

What is the 2nd messenger to Phospholipase C-B?

Answer 2

-Diacylglycerol (DAG)
-IP3

Question 3

What does IP3 do?

Answer 3

-gates (opens) calcium release from channel in ER
-this calcium binds to protein kinase C (PKC) changing function

Question 4

What does a change in free calcium levels do to the cell?

Answer 4

Inside cell calcium concentration is 10-7
-increase to 10-6 rapidly activates certain cellular functions such as release of Ca+2 from the ER as a result of Gaq activation

Question 5

What does an increase in calcium concentration lead to?

Answer 5

-Calmodulin binds Calcium which induced conformational changes in CaM
-this CaM binds Calmodulin-dependent kinases (CaM kinases)

Question 6

What is PLCy activated by?

Answer 6

-tyrosine phosphorylation
-RTK (receptor tyrosine kinases)

Question 7

What is PLCb activated by?

Answer 7

-interactions with trimeric G proteins (GPCRs) ex. Gq

Question 8

What do Phosphatidylinositol 3-kinases (activated by RTK) (PI3-Kinase) do?

Answer 8

-Phosphorylates PIP2 to PIP3
-PIP3 is a 2nd messenger of signaling pathways

Question 9

What are some pathways that PIP3 activates?

Answer 9

-Akt/Protein kinase B (PKB)
-focused with cancer studies

Question 10

How does the initiation of DNA replication occur?

Answer 10

-DNA melting (generates replication forks)
-called origins of replication (ori) 6x10^4 in humans
-cells initiating replication is licensed to once per cell cycle

Question 11

What needs to form in order for licensing to occur?

Answer 11

-during G1 CDT1 and CDC6 recruit ORC
-ORC1-6 (origin of replication complex)
-MCM2-7 (6 proteins; mini chromosome maintenance complex)
-activation of both fires replication; done by cyclin-dependent kinase (CDK) phosphorylation

Question 12

When phosphorylation of licensing factors happens, what is next?

Answer 12

-Cdc6 and Cdt1 are released
-MCM helicase is activated
-Phosphorylated forms can no longer ‘license’

Question 13

Once replication has been initiated, what occurs?

Answer 13

-ssDNA opens up (Cdc45+GINS)
-replcation forks diverge and ssDNA is stabilized by replication protein A (RPA)
-replisome is formed

Question 14

What is RFC?

Answer 14

-Replication Factor C
-connects 2 PCNA (Proliferating Cell Nuclear Antigen) molecules together
-acts as a trombone bubble that grows and shrinks as DNA is being replicated

Question 15

What is the Replisome?

Answer 15

-consists of 2 polymerase III enzymes, Primosome, and DNA unwinding proteins
-keeps both DNA strands being replicated are in the correct (same) orientation

Question 16

What does Cyclin A do?

Answer 16

-starts working at beginning of DNA synthesis
-binds CDK2 (licensing factor)
-indirectly regulated by p53 and p21

Question 17

What are some anticancer drugs that are developed?

Answer 17

-Fluorouracil (5FU) works by inhibiting Thymidylate synthase to prevent Dihydrofolate synthesis
-Methotrexate directly inhibits Dihydrofolate Reductase (DHFR)

Question 18

What do Alkylating agents do?

Answer 18

-cause double stranded and single stranded breaks in DNA which cause damage
-developed as platinum based chemotherapeutics (single-stranded break)

Question 19

What is the phenomenon associated with the Philadelphia Chromosome?

Answer 19

-Philadelphia chromosome and BCR-ABL
-unequal exchange occurs
-causes Abl kinase to be active at all times (auto-inhibiton function is lost)
-uncontrolled cell proliferation
-treatment includes Gleevrc (imatinib), Dasatinib, and Nilotinib (inhibits BCR-ABL)