MCG Test 3 Flashcards
G1 chromosome number
2N
Prophase
First stage of mitosis. Chromosomes condense. Nuclear envelope disintegrates.
S Phase Chromosome Number
Between 2N and 4N
G2 Chromosome number
4N
Metaphase
Sister chromatids line up at the metaphase plate.
Anaphase
Sister chromatids (attached to microtubule spindle), begin to separate.
Telophase
Sister chromatids have completely separated. Cytokinesis begins to occur. Nuclear envelope begins to form again.
Meiosis Ploidy
2N -> 4N during S
4N-> 2X2N (Meiosis 1)
2X2N -> 4X1N (Meiosis 2)
What is the difference between Mitosis and Meiosis 1?
Instead of sister chromatids, homologous chromosomes line up and recombine to increase genetic diversity.
Synaptonemal complex
Where homologous chromosomes come together to cross over.
Speed of meiosis regulated by…?
Meiosis 1. Slow to enable max genetic diversity via recombination.
CDKs and Cyclins
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.
Cyclin-CDK Pairings in the Cell Cycle
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.
How is CDK activated?
When Cyclin binds, t-loop is exposed. CAK (CDK activating kinase) phosphorylates it.
Wee1
Wee1 adds two inhibiting phosphates to CDK. These phosphates electrostatically repel ATP binding.
CDC25A, CDC25B, CDC25C
These activating phosphatases remove Wee1’s inhibitory phosphates and cause CDK to be active.
Cip family of CDK inhibitors
p21, p27, p53. These CDK inhibitors inactivate the whole CDK+Cyclin complex. These are different than the INK4 family, which displace cyclin completely.
INK4 family of CDK inhibitors
These inhibitors displace cyclin to inactive the CDK-Cyclin complex.
How are cyclins degraded?
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.
Ras pathway
GF binds to RTK. Cross-phosphorylation, autophosphorylation, GRB2, SOS, Ras, Raf, Mek, Erk.
What does Erk do?
Erk phosphorylates cyclin D. Phosphorylated cyclin D will bind to CDK4+CDK6 to phosphorylate RB.
Rb method of action/inhibition
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.
E2F
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.
Why is Methionine an important amino acid?
Enables the methylation of critical compounds like epinephrine, creatine, carnitine, DNA/RNA.
How does methionine methylate stuff?
Methionine + ATP -> SAM (S-adenosyl methionine) + 3 P.
Via SAM synthase.
SAM will methylate stuff and become SAH.
SAH+H20 –> Homocysteine and Adenosine.
How is homocysteine converted back to methionine?
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.
Homocysteine Transulfuration (Cysteine synthesis)
Occurs in addition to conversion back to methionine.
Homocysteine + Serine -> Cystathionine. Via Cystathionine synthase.
Cystathionine –> NH4 + alpha Ketobutyrate + Cysteine. (Via Cystathionase and B6)
Homocystinuria
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.
Vitamin B12 Structure
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.
Propionyl CoA Metabolism
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).
Methylmalonyl Aciduria
Defect in Methylmalonyl mutase or B12-adenosine (lack of synthesis due to faulty transferase) that causes methylmalonyl CoA to accumulate.
Folate reduction
Folate –> DHF –> THF
All via DHF reductase.
Methylation of THF
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.
Serine Transhydroxy Methylase Reaction
Serine + THF –> Glycine + N5N10 Methylene THF. Via Serine transhydroxymethylase and B6.
What happens to glycine after it’s generated by serine transhydroxymethylase?
It can be turned into N5N10 Methylene THF.
Histidine and THF
Can be used to create N-formino Glutamate, which can then become N5formino THF
Pernicious Anemia
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.
What are N5 methyl THF, N5N10 Methylene THF, and N5N10 methenyl THF used for?
N5MeTHF- regenerate methionine from homocysteine.
N5N10 Methylene THF- Create TMP from UMP.
N5N10 Methenyl THF- Create purine rings.
TMP Generation Reaction
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.
