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First Aid: Biochemistry > Principles: Molecular Biochemistry > Flashcards

Principles: Molecular Biochemistry Flashcards

1
Q

Are histones positively or negatively charged?

What histones make up the nucleosome “bead”?

A

Histones are positive - they bind DNA, which is negative.

The nucleosome core is an octamer of H2A, H2B, H3, and H4 (x2 for each)

Think of chromatin structure as “beads on a string”.

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2
Q

What histone binds nucleosomes and “linker DNA” to stabilize them?

A

H1.

H1 is the only histone that is not in the nucleosome core.

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3
Q

How does chromatin structure change during mitosis?

When does histone synthesis occur?

A

DNA condenses to form chromosomes during mitosis.

DNA and Histone synthesis both occur during S phase.

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4
Q

What is a name for condensed, transcriptionally inactive chromatin?

How about less condensed, active, sterically accessible chromatin?

A

Inactive and dense = HeteroChromatin (Highly Condensed)

Less condensed and transcriptionally active = Euchromatin (Eu = true, “truly transcribed”)

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5
Q

What bases are methylated in DNA replication, and why?

A

Template strand cytosine and adenine are methylated in DNA replication.

Allows mismatch repair enzymes to distinguish between old and new strands in prokaryotes.

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6
Q

Where can DNA be methylated to repress transcription?

A

CpG islands.

CpG Methylation Makes DNA Mute

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7
Q

What effect does histone methylation have on DNA transcription?

A

Usually reversibly represses DNA transcription, but can activate it in some cases.

Histone Methylation Mostly Makes DNA Mute.

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8
Q

What effect does histone acetylation have on DNA transcription?

A

Relaxes DNA coiling, allowing for transcription.

Histone Acetylation makes DNA Active.

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9
Q

Which bases are purines and pyrimidines respectively?

How many rings does each have?

A

PURines (A, G) - 2 rings. (“PURe As Gold)

PYrimidines (C, T, U) - 1 ring. (“CUT the PY”)

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10
Q

How do thymine and uracil differ?

How about cytosine and uracil?

A

Thymine has an extra methyl group

Deamination of cytosine forms uracil

Uracil in RNA, thymine in DNA.

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11
Q

What base pair increases the melting point of DNA

A

G-C base pairs. They have 3 H-bonds, stronger than the two H-bonds of A-T.

Greater GC content increases DNA melting point.

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12
Q

What amino acids are necessary for purine synthesis?

A

GAG

Glycine

Aspartate

Glutamine

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13
Q

What is the difference between nucleosides and nucleotides?

A

NucleoSide = base + (deoxy)ribose (Sugar)

NucleoTide = base + (deoxy)ribose + phosphaTe, linked by 3’-5’ phosphodiester bond.

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14
Q

What is the general mechanism of purine synthesis?

A

Start with sugar + phosphate (PRPP)

Add base

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15
Q

What is the general mechanism of pyrimidine synthesis?

A

Make temporary base (orotic acid)

Add sugar + phosphate (PRPP)

Modify base

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16
Q

What amino acid is requried for de novo pyrimidine synthesis?

A

Aspartate

17
Q

What two metabolic pathways is carbamoyl phosphate involved in?

A

Carbamoyl phosphate is required for:

De novo pyrimidine synthesis

Urea cycle

18
Q

How are deoxyribonucleotides formed?

A

First ribonucleotides are synthesized.

Then they are converted to deoxyribonucleotides by ribonucleotide reductase.

19
Q

What enzyme does Leflunomide inhibit?

A

Dihydroorotate dehydrogenase.

20
Q

What enzyme does Mycophenolate inhibit?

A

IMP dehydrogenase

21
Q

What enzyme does ribavirin inhibit?

A

IMP dehydrogenase

22
Q

What enzyme does hydroxyurea inhibit?

A

Ribonucleotide reductase

23
Q

What enzyme does 6-mercaptopurine inhibit?

What is its prodrug?

A

Conversion from PRPP to IMP. (AKA de novo purine synthesis)

Prodrug: Azathioprine

24
Q

What enzyme does 5-fluorouracil inhibit?

A

Thymidylate synthase (reduces deoxythymidine monophosphate, dTMP)

25
Q

What drug inhibits dihydrofolate reductase in humans?

A

Methotrexate

26
Q

What drug inhibits dihydrofolate reductase in bacteria?

A

Trimethoprim

27
Q

What drug inhibits dihydrofolate reductase in protozoa?

A

Pyrimethamine

28
Q

What is adenosine deaminase deficiency?

A

Deficiency of the enzyme that converts adenosine to inosine.

Excess ATP and dATP imbalances nucleotide pool via feedback inhibition of ribonucleotide reductase.

This prevents DNA synthesis and thus reduces leukocyte count.

One of the major causes of autosomal recessive SCID.

29
Q

What is Lesch-Nyhan Syndrome?

A

Defective purine salvage due to absent HGPRT, which converts hypoxanthine to IMP and guanine to GMP.

Excess uric acid production and de novo purine synthesis. X-linked recessive.

:HGPRT Hyperuricemia, Gout, Pissed off (aggression, self-mutilation), Retardation, DysTonia

Treat with allopurinol or febuxostat.

First Aid: Biochemistry (7 decks)

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