MCG Test 3

Question 0

G1 chromosome number

Answer 0

2N

Question 1

Prophase

Answer 1

First stage of mitosis. Chromosomes condense. Nuclear envelope disintegrates.

Question 2

S Phase Chromosome Number

Answer 2

Between 2N and 4N

Question 3

G2 Chromosome number

Answer 3

4N

Question 4

Metaphase

Answer 4

Sister chromatids line up at the metaphase plate.

Question 5

Anaphase

Answer 5

Sister chromatids (attached to microtubule spindle), begin to separate.

Question 6

Telophase

Answer 6

Sister chromatids have completely separated. Cytokinesis begins to occur. Nuclear envelope begins to form again.

Question 7

Meiosis Ploidy

Answer 7

2N -> 4N during S
4N-> 2X2N (Meiosis 1)
2X2N -> 4X1N (Meiosis 2)

Question 8

What is the difference between Mitosis and Meiosis 1?

Answer 8

Instead of sister chromatids, homologous chromosomes line up and recombine to increase genetic diversity.

Question 9

Synaptonemal complex

Answer 9

Where homologous chromosomes come together to cross over.

Question 10

Speed of meiosis regulated by…?

Answer 10

Meiosis 1. Slow to enable max genetic diversity via recombination.

Question 11

CDKs and Cyclins

Answer 11

Regulate the cell cycle. CDK is the catalytic subunit and cyclin is the regulatory subunit. When cyclin binds, it opens up CDK’s substrate binding site and provides access to an ATP binding domain.

Question 12

Cyclin-CDK Pairings in the Cell Cycle

Answer 12

G1- CDK4+Cyclin D, CDK6+Cyclin D, CDK2+Cyclin E.

S- CDK2+Cyclin A.

G2- CDK1+ Cyclin A, CDK1+Cyclin B.

CDK levels are fixed, but cyclin levels vary. They’re subject to increased transcription and increased degradation.

Question 13

How is CDK activated?

Answer 13

When Cyclin binds, t-loop is exposed. CAK (CDK activating kinase) phosphorylates it.

Question 14

Wee1

Answer 14

Wee1 adds two inhibiting phosphates to CDK. These phosphates electrostatically repel ATP binding.

Question 15

CDC25A, CDC25B, CDC25C

Answer 15

These activating phosphatases remove Wee1’s inhibitory phosphates and cause CDK to be active.

Question 16

Cip family of CDK inhibitors

Answer 16

p21, p27, p53. These CDK inhibitors inactivate the whole CDK+Cyclin complex. These are different than the INK4 family, which displace cyclin completely.

Question 17

INK4 family of CDK inhibitors

Answer 17

These inhibitors displace cyclin to inactive the CDK-Cyclin complex.

Question 18

How are cyclins degraded?

Answer 18

Degraded by the ubiquitin proteasome system. SCF is always active, which degrades phosphorylated cyclin. Cyclin E will phosphorylate cyclin D and tag it for degradation.

Also, the anaphase promoting complex will degrade cyclins E and A, but needs cofactors to function.

Question 19

Ras pathway

Answer 19

GF binds to RTK. Cross-phosphorylation, autophosphorylation, GRB2, SOS, Ras, Raf, Mek, Erk.

Question 20

What does Erk do?

Answer 20

Erk phosphorylates cyclin D. Phosphorylated cyclin D will bind to CDK4+CDK6 to phosphorylate RB.

Question 21

Rb method of action/inhibition

Answer 21

When Rb is hypophosphorylated, it stays bound to E2F (transcription factor). No DNA synthesis.
When Rb is phosphorylated, some E2F is free to transcriptionally upregulate Cyclin E. This will activate CDK2, which will continue to phosphorylate Rb.
When Rb is hyperphosphorylated. E2F will migrate to the nucleus and upregulate DNA polymerase alpha and other S phase promoters.

Question 22

E2F

Answer 22

A transcription factor that, when partially free from Rb, will upregulate Cyclin E, thus activating CDK2. CDK2 will cause more E2F to be activated, which will then upregulate proteins that cause DNA replication (DNA polymerase alpha, etc). E2F also activates Cyclin A+CDK2, which will initiate the whole DNA polymerase complex and will remove licensing factors that have accumulated during G1 to show where origins have been fired.

Question 23

Why is Methionine an important amino acid?

Answer 23

Enables the methylation of critical compounds like epinephrine, creatine, carnitine, DNA/RNA.

Question 24

How does methionine methylate stuff?

Answer 24

Methionine + ATP -> SAM (S-adenosyl methionine) + 3 P.
Via SAM synthase.

SAM will methylate stuff and become SAH.

SAH+H20 –> Homocysteine and Adenosine.

Question 25

How is homocysteine converted back to methionine?

Answer 25

Homocysteine + N5 Methyl THF –> Methionine + THF.

This occurs by way of Vitamin B12, which takes the methyl group from THF, binds it, and then transfers it to homocysteine to become methionine.

Question 26

Homocysteine Transulfuration (Cysteine synthesis)

Answer 26

Occurs in addition to conversion back to methionine.

Homocysteine + Serine -> Cystathionine. Via Cystathionine synthase.

Cystathionine –> NH4 + alpha Ketobutyrate + Cysteine. (Via Cystathionase and B6)

Question 27

Homocystinuria

Answer 27

Disease caused mostly by an inborn error that decreases cystathionine synthase. A reduction in B12 or folate could also cause homocystinuria, because they’re used to turn homocysteine back into methionine.

Question 28

Vitamin B12 Structure

Answer 28

Cobalamin has a corrin ring structure with 6 substrates bound to a central cobalt. Four of the substrates are pyrol rings. The sixth substrate can be -OH, -CH3, or -Adenosine, which is synthesized with ATP and Transferase.

Question 29

Propionyl CoA Metabolism

Answer 29

Isoleucine, Methionine, Valine, Odd Chain Fatty Acids –> Propionyl CoA.

Propionyl CoA —-> D-Methylmalonyl CoA —-> L-Methylmalonyl CoA. Via methylmalonyl racimase.

L-Methylmalonyl CoA –>Succinyl CoA (which enters TCA cycle). Via Methylmalonyl CoA mutase and adenocobalamin (B12).

Question 30

Methylmalonyl Aciduria

Answer 30

Defect in Methylmalonyl mutase or B12-adenosine (lack of synthesis due to faulty transferase) that causes methylmalonyl CoA to accumulate.

Question 31

Folate reduction

Answer 31

Folate –> DHF –> THF

All via DHF reductase.

Question 32

Methylation of THF

Answer 32

THF can be methylated with Serine to create N5 methylene THF, which can then be turned irreversibly into N5Methyl THF, or reversibly into N5N10 methenyl THF.

Question 33

Serine Transhydroxy Methylase Reaction

Answer 33

Serine + THF –> Glycine + N5N10 Methylene THF. Via Serine transhydroxymethylase and B6.

Question 34

What happens to glycine after it’s generated by serine transhydroxymethylase?

Answer 34

It can be turned into N5N10 Methylene THF.

Question 35

Histidine and THF

Answer 35

Can be used to create N-formino Glutamate, which can then become N5formino THF

Question 36

Pernicious Anemia

Answer 36

There is no IF (intrinsic factor) for B12 absorption. Thus, B12 won’t accept a methyl group from 5MeTHF, causing it to accumulate. The body responds by sending N5N10 methylene and methenyl THF to become 5meTHF. No purine generation, no TMP generation, and no methionine synthesis.

Question 37

What are N5 methyl THF, N5N10 Methylene THF, and N5N10 methenyl THF used for?

Answer 37

N5MeTHF- regenerate methionine from homocysteine.
N5N10 Methylene THF- Create TMP from UMP.
N5N10 Methenyl THF- Create purine rings.

Question 38

TMP Generation Reaction

Answer 38

dUMP -> dTMP. Via thymadinic synthase and N5N10 Methylene THF.

N5N10 Methylene THF will donate a methyl to become DHF, which is reduced to THF by DHF reductase.
THF is turned back into N5N10 Methylene THF by Serine and Serine Transhydroxymethylase.