Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

* DIT each session > Day 9.3 Biochem > Flashcards

Day 9.3 Biochem Flashcards

1
Q

Organizational relationship bt DNA and chromosomes

A

DNA –> nucleosomes –> chromatin –> chromosomes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is a nucleosome?

A

Group of 8 histones w DNA wrapped around twice.

2 each of H2A, H2B, H3, H4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What AAs make up the histone octamer

A

Mostly lysine and arginine, which are positively charged, and therefore ionically bind the negatively charged DNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Which histone is not part of the histone octamer (the nucleosome core)?

A

H1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

When does DNA condense?

A

In mitosis, it condenses to form mitotic chromosomes.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Heterochromatin, Euchromatin

A

HeteroChromatin = Highly Condensed.
Transcriptionally inactive, sterically inaccessible.

Euchromatin (Eu = True-ly transcribed)
Less condensed, transcriptionally active and sterically accessible.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How do additions to lysine affect DNA transcription?

A

Adding an acetyl or removing a methyl group decreases DNA affinity for the histone, causing it to become euchromatin.
Euchromatin = transcriptionally active.

So, if you add acetyl or remv methyl, you can make proteins!

If you do the opposite- remove acetyl or add methyl, you make the DNA have MORE affinity for the histone –> heterochromatin.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Methylation of DNA strands during replication

A

On the template (parent) strand, cytosine and adenine are methylated during DNA replication.

This allows mismatch repair enz to distinguish b/t the old and new strands- it’s more likely that the new strand is going to be the one with the problem.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What effect does hypermethylation have on the transcription of DNA

A

Adding methyl groups causes DNA to become condensed into Heterochromatin, so transcription can’t occur.
Hypermethylation inactivates DNA transcription.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What effect does histone acetylation have on DNA transcription?

A

Histone acetylation relaxes DNA coiling (changes it to euchromatin), which allows transcription to take place.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Methylation effect on DNA

Acetylation effect on DNA

A

Methylation makes DNA Mute (heterochromatin, highly condensed/transcriptionally inactive form)
Methyl groups are sml, so they allow histones to stay together.

Acetylation makes DNA Active
(euchromatin, transcriptionally active form)
Acetyl groups are bigger, so they push DNA away from histones.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the nucleotides? How many rings? What’s in DNA vs RNA

A

Purines: A, G; 2 rings

Pyrimidines: C, T, U (1 ring- Py (pies) have a single ring)

DNA = A, G, C, T
RNA = A, G, C, U
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Which nucleotide has a ketone?

Which has a methyl?

A

Guanine has a ketone

Thymine has a meTHYl

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How is uracil made?

A

Deamination of cytosine.

The NH2 is taken off of cytosine and replaced w an O.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Number of bonds between the nucleotides

A

G-C has 3 H+ bonds
A-T has 2 H+ bonds

So, DNA with higher G-C content is harder to melt, therefore has a HIGHER melting temp.
(Note that DNA length also affects melting temp- longer DNA has higher)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Difference bt nucleotide and nucleoside

A 
Nucleoside = Sugar(ribose) + Base
Nucleotide = Sugar(ribose) + Base + Phosphate(mono/di/tri)

Nucleotides are linked by 3’ to 5’ phosphodiester bonds.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Adenine vs adenosine

Guanine vs guanosine

A

the -sine is the nucleoside (Base + sugar).
otherwise, it just means the base.
So adenine and guanine are bases.
Adenosine and Guanosine are the nucleosides (base + sugar).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What AAs are necessary for purine synthesis? What are the carbon sources?

A

Glycine
Aspartate
Glutamate

CO2, glycine, and THF are the sources of carbons.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is necessary for Pyrimidine synthesis?

A

Aspartate and Carbamoyl phosphate
The precursors for carbamoyl phosphate are CO2 (for the carbon) and glutamine (for the nitrogen)
Also need THF to make it.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Is glycine needed in purine or pyrimidine synthesis?

A

Only purine synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are the precursors for purines? pyrimidines?

A

Purines: IMP precursor
IMP –> AMP
IMP –> GMP (this is by IMP dehydrogenase)

Pyrimidines: Orotate precursor, PRPP is added later.
Orotic acid –> OMP –> UMP –> UDP
UDP –> > > > dTMP (DNA) (this is by thymidylate synthase)
UDP –> CTP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Which is made first, ribonucleotides or deoxyribonucleotides?

A

Ribonucleotides.

The deoxyribonucleotides come from the ribonucleotides. Ribonucleotide reductase is the enz that converts them.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What 2 pathways use carbamoyl phosphate?

A

Denovo pyrimidine synthesis

Urea cycle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

OTC deficiency

A

Ornithine transcarbamoylase (OTC) normally converts carbamoyl phosphate to Citurulline, which is part of the urea cycle.

In OTC deficiency, the carbamoyl phosphate cannot be converted to citrulline and builds up, so it enters the other pathway it’s part of- denovo pyrimidine synthesis. Carbamoyl phosphate is converted to orotic acid.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

How is carbamoyl phosphate made?

A

ATP + CO2 + Glutamine

and the enzyme CPS-2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What is the rate-limiting step in pyrimidine synthesis?

A

CPS-2 enz, which converts ATP, CO2, and glutamate into carbamoyl phosphate.
(Carbamoyl phosphate is then converted to orotic acid and pyrimidines are made from that.)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

How does the order differ in pyrimidine vs purine synthesis?

A

Purines:

  1. Start w Sugar and PRPP (phosphate)
  2. Add base

Pyrimidines

  1. Start w (temporary) base (Orotic acid)
  2. Add Sugar and PRPP (phosphate)
  3. Modify the base

When you build a pyramid, you need to start w a base!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What are the steps in pyrimidine synthesis?

A

Orotic acid + PRPP (+orotic acid phosphoribosyltransferase)
OMP (+5’-phosphate decarboxylase)
UMP
UDP (+ribonucleotide reductase)

UDP –> CTP
or
UDP –> dUDP –> dUMP (+THF and thymidylate synthase) –> dTMP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What role does folate play in pyrimidine synthesis?

A

Methylene THF is needed to convert dUMP to dTMP (final pyrimidine product), along with the enz thymidylate synthase.

In this process, methylene THF is converted to DHF.

DHF is converted back to THF by the enz dihydrofolate reductase. (And the THF is converted to methylene THF)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What are the steps in purine synthesis?

A

Ribose-5-P (+PRPP synthetase)
PRPP (+gluamine PRPP amidotransferase)
»+Hypoxanthine –»»
IMP

IMP –> AMP
or
IMP (+IMP dyhydrogenase) –> GMP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What is the rate-limiting step of purine synthesis?

A

Glutamine PRPP amidotransferase, which converts PRPP to the next step in the pathway to make IMP.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What does ribonucleotide reductase do? What drug blocks it?

A

RNR converts UDP –> > > dTMP

(It also makes deoxy-nucleotides from the other ribonucleotides)

Blocked by Hydroxyurea
(anti-cancer, used in sickle cell)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What does PRPP synthetase do? What drug blocks it?

A

PRPP synthetase converts Ribose-5-P to PRPP in the first step of denovo purine synthesis.

Blocked by 6-MP (mercaptopurine)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

What does Thymidylate Synthase do?

What drug blocks it?

A

Converts dUMP to dTMP (folate is also req’d)

Blocked by 5-FU (anti-cancer)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

What does IMP dehydrogenase do?

What drug blocks it?

A

Converts the IMP to GMP in purine synthesis.

Blocked by Mycophenylate (an immunosuppressant)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What does Dihydrofolate Reductase do?

What drugs block it?

A

DHFR converts DHF to THF (need to regenerate the THF for pyrimidine synthesis)
MTX blocks it in eukaryotes
TMP blocks it in prokaryotes (so use for bacterial infections)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What causes orotic aciduria?

A

Can’t convert Orotic Acid to UMP in the denovo pyrimidine synth pathway.

Caused by defect in one of two enz:
1. orotic acid phosphoribosyltransferase (which converts orotic acid to OMP)
2. orotidine 5’-phosphate decarboxylase
(which converts OMP to UMP)

Auto-recessive.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Findings in orotic aciduria

A

Since you can’t convert orotic acid to UMP, orotic acid builds up, and there is increased orotic acid in urine.

There is also megaloblastic anemia (which, unlike most of the time, does NOT improve w admin of folate or B12)

And FTT.

No hyperammonia (vs OTC def- which is also increased orotic acid)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

If there is increase orotic acid in the urine, what is the next thing you should check?

A

Ammonia levels.

Hyperammonia - OTC deficiency (bc can’t get rid of it in the urea cycle)

No hyperammonia - orotic aciduria (urea cycle is fine)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Rx for orotic aciduria?

A

Oral uridine administration

Just bypass the pathway w the faulty enz and start pyrimidine synthesis w the UMP.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

What is the goal of breaking down purines?

A

Turn them into uric acid, which can be excreted in urine.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

What can Guanine be converted to?

A

GMP (guanylic acid)
Guanosine (nucleoside)
Xanthine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

What can Hypoxanthine be converted to?

A

IMP (Inosinic acid)
Inosine
Xanthine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

What can Adenine be converted to?

A

AMP (adenylic acid) only.

Converted by enz APRT (the equivalent of HGPRT, which converts Hypoxanthine and Guanine)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

What is IMP converted to?

A

AMP or GMP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

What two things can xanthine be made from?

A

Guanine or Hypoxanthine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

What does xanthine oxidase do?

A

Converts Hypoxanthine to Xanthine, and also converts Xanthine to Uric Acid (which is excreted in urine)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

What drug blocks xanthine oxidase?

A

Allopurinol. Since it doesn’t allow uric acid to be formed, it is good for treating (chronic) gout.
Can also be used for the gout and hyperuricemia of Lesch-Nyhan syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

What is Lesch-Nyhan syndrome?

A

Defective purine salvage d/t absence of HGPRT (which converts hypoxanthine to IMP and guanine to GMP).
Buildup of guanine and hypoxanthine mean that they are both converted to xanthine, which makes a lot of uric acid.

Findings: Hyperuricemia, gout, MR, self-mutilation (esp lip-biting), choreoathetosis, aggression.

X-linked Recessive

HGPRT = He’s got purine recovery trouble

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

What does HGPRT do?

A

H = hypoxanthine
G = guanine
Converts hypoxanthine and guanine to IMP and GMP respectively.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

What is the treatment for Lesch-Nyhan

A

Allopurinol, which inhibits xanthine oxidase, so there is less uric acid in the blood.
Only fixes the gout and hyperuricemia tho, not the MR, CNS issues.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

What drugs are metabolized by xanthine oxidase, and therefore will have increased toxicity if the pt is also taking allopurinol?

A

6-MP (anti-cancer), and the related drug Azithoprine.
These are both metabolized by xanthine oxidase.
Allopurinol inhibits xanthine oxidase, so XO won’t be able to metabolize 6-MP as usual, so there will be more toxicity from 6-MP since it doesn’t get metabolized.
(Toxic to bone marrow, GI, liver)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

What is adenosine converted to?

A

AMP
or Inosine
(and inosine is then converted to hypoxanthine)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

What enz converts adenosine to inosine?

A

Adenosine Deaminase (ADA)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

What is adenosine deaminase (ADA) deficiency?

A

Can’t convert adenosine to inosine.
So excess adenosine (and therefore excess AMP)

Excess ATP and dATP cause imbalance in the nucleotide pool via feedback inhibition of ribonuceloside reductase (RNR converts ribo to deoxyrib)

This prevents DNA synth and therefore decreases lymphocyte count (a lot).
Mjr cause of SCID

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

Main sx of SCID, cause

A 
SCID- severe combined immunodeficiency.
Severe recurrent infections
Chronic diarrhea
FTT
No thymic shadow on xray

1st dz to be treated by experimental human gene therapy.

Can be caused by 7 different genetic problems, one of which is Adenosine Deaminase (ADA) deficiency.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

Silent mutation

A

Can of one base pair (often in 3rd wobble position) that results in the same AA being created.
Since AA is the same, not very problematic.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

Missense mutation

A

Mutation in a base pair that results in a different AA- but one that is similar to the structure of the original AA (aka it’s a conservative mutation)
Not very problematic, unless the mutation is at an active site- then can make the active site unable to bind/non-fnl.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

Nonsense mutation

A

Stop the nonsense!

Base pair change that results in a stop codon being produced instead of the normal AA.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

What are the 3 stop codons?

A

UGA
UAG
UAA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

Frameshift mutation

A

Change (insertion or deletion) of a base pair such that the 3-base pair frame is shifted, so all AAs downstream of the shift are misread.
Usu results in truncated, non-fnl protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

Rank the severity of damage of DNA mutations

A
  1. Nonsense (worst)
  2. Missense
  3. Silent
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

Origin of DNA replication

A

Particular seq in genome where the DNA replication begins
Prokaryotes: 1 origin
Eukaryotes: multiple origins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

Replication fork

A

Y-shaped region along DNA template where the leading and lagging strands are synthesized.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

Helicase

A

Unwinds DNA template at the replication fork.

If I were an enz I would be helicase… ;)

66
Q

SSB proteins

A

Single-stranded binding proteins

Hold the two DNA strands apart at the fork to prevent them from re-annealing

67
Q

DNA Topoisomerase II

A

aka DNA gyrase

Creates a nick in the DNA to relieve the supercoils created during replication by helicase.

68
Q

What abx inhibit DNA gyrase?

A

(inhibit prokaryotic topoisomerase II):
Flouroquinolones
Inhibition means the bacteria are unable to replicate and divide.

69
Q

Primase

A

Makes the RNA primer on which DNA polymerase III will initiate replication

70
Q

DNA Polymerase III

A

Prokaryotic only.
Starts at RNA primer put down by primase.
Elongates leading strand by adding deoxynucelotides to the 3’ end.
Elongates lagging strand until it reaches the primer of the preceding fragment.
3’ –> 5’ exonuclease acitivity “proofreads” each added nucleotide. (But synthesis is 5’ –> 3’ as always)

71
Q

DNA Polymerase I

A

Prokaryotic only.
Excises the RNA primer w a 5’ –> 3’ exonuclease.
Degrades the RNA primer and fills in the gap w DNA

72
Q

DNA ligase

A

Seals strands together after DNA Polym I has removed the RNA primer and filled in the gaps.

73
Q

What are the DNA polymerases for eukaryotes (and what do they do)?

A

alpha: synth’s RNA primer and replicates lagging strand
beta, epsilon: repair DNA
gamma: replicated mito DNA
delta: replicates leading strand

74
Q

What are the anti- topoisomerase Ab, and what dz are they assoc w?

A

Anti- Scl-70

A/w diffuse scleroderma

75
Q

What cancer drug inhibits the eukaryotic topoisomerases?

A

Etopiside

eTOPiside inhibits TOPoisomerases

76
Q

Telomerase

A

Adds DNA to the 3’ ends of the chromosome to avoid loss of genetic material every time there is replication.
TTAGGG is the seq added.

In adults, this only occurs in stem cells and immune cells (things that need to divide a lot)

Also occurs in cancer- imp step for neoplastic transformation.

77
Q

Enz w 5’ –> 3’ exonuclease activity

A

DNA polymerase I
Excises the RNA primer
(then degrades it and fills in gap w DNA)

78
Q

Enz w 3’ –> 5’ exonuclease activity

A

DNA polymerase III
Adds nucleotides, elongating the leading and lagging strands. The exonuclease “proofreads” each added nucleotide.

Note: even tho the exonuclease is backwards, synthesis (as always) goes in the 5’ –> 3’ direction.

79
Q

What are the three methods of single strand DNA repair?

A

Nucleotide excision repair
Base excision repair
Mismatch repair

(for dbl strand repair, there is non-homologous end-joining)

80
Q

Nucleotide excision repair

A

Specific endonucleases rls the oligonucleotide-containing bases that are dmgd. This is for a small segment of DNA (vs base excision, which is just for a base)
DNA polymerase fills in the gap and ligase reseals it.

81
Q

Base excision repair

A

Specific glycolases recognize and remv the dmgd base, AP endonuclease cuts DNA at the apyrimidinic site, empty sugar is remvd, and the gap is filled in and resealed (polymerase, ligase)
This is for one base (vs nucleotide excision, which is for a segment)
Imp in repair of spontaneous/toxic deamination.

82
Q

Mismatch repair

A

When DNA is made, the old strand has methyl groups, but the new strand has not be methylated yet- so this is how it’s recognized as new.
The unmethylated, new DNA is recognized, and mismatched nucleotides are removed. Then the gap is filled and sealed.

83
Q

What are dz’s caused by defects in DNA repair?

A

Xeroderma pigmentosa (nucleoside excision repair defect)
Bloom’s syndrome
HNPCC Hereditary NonPolyposis Colorectal Cancer (mismatch repair defect)
BRCA1 and BRCA2
Ataxia-Telangiectasia (Non-homologous end joining defect)

84
Q

What is the DNA repair mechanism that deals with double-stranded repair? How dies it work?

A

Non-homologous end-joining.
Brings together 2 ends of DNA fragments
No reqmt for homology
Caused by x-ray, CT radiation

85
Q

Xeroderma pigmentosum

A

Dry skin w melanoma and other skin cancer, children of the night.

D/t nucleotide excision repair defect, which prevents the repair of thymidine dimers (which are caused by exposure to UV)

86
Q

Ataxia-Telangiectasia

A 
Triad of:
Cerebellar defects (ataxia)
Spider angiomas (telangiectasia)
IgA deficiency (so immunodeficient)

Caused by defect in non-homologous end joining (DNA repair)
Insensitivity to ionizing radiation

Gait ataxia starts at 1-2 years, need to dx right away, before the telangiectasias (which happen at 5yo).
No smooth pursuit, aFP may be elevated (after 8mo old)

87
Q

Bloom’s syndrome

A

HPS to sunlight
Leukemias and lymphomas common
Avg age of cancer onset is 25
d/t DNA repair defect

88
Q

HNPCC

A

Hereditary NonPolyposis Colorectal Cancer

Caused by auto-dom mutation of DNA mismatch repair genes.

80% progress to colorectal cancer
proximal colon always involved.

89
Q

BRCA1 and BRCA2

A

Tumor suppressor genes
Loss of fn –> cancer (and BOTH alleles must be lost)

Normal gene product is DNA repair protein, so if mutated, there will be defective DNA repair.

BRCA1 causes breast and ovarian cancer
BRCA2 causes breast cancer

90
Q

What direction are DNA, RNA, and proteins read and made?

A

5’ –> 3’ direction
mRNA is read 5’ –> 3’
Protein synth is N to C

The incoming nucleotide (the one being added) has the triphosphate on it, which is the energy source for the bond that’s about to be made.

The triphosphate bond is attacked by the 3’OH on the existing strand.

91
Q

Drugs that block DNA replication (HIV, chemo) often have what biochemical modification to their DNA?

A

the 3’OH on the existing DNA strand is modified, meaning that the 3’OH can’t attach the triphosphate of an incoming nucleotide in order to add it to the chain (aka chain termination happens, bc nothing more can be added)

92
Q

What are the types of RNA?

A

rRNA (most abundant)
mRNA (longest)
tRNA (smallest)

RNA is rampant, massive, tiny
rRNA has to be the most abundant, bc it makes up the ribosomes!
mRNA has to be the longest, bc some genes are super long

93
Q

Start codon, and what it codes for (which AA)

A

AUG
(AUG inAUGurates protein synthesis)
Rarely, GUG can also start things.

Eukaryotes: AUG codes for methionine
(the methionine may be removed before the translation is completed tho, making it look like it started w something else!)

Prokaryotes: AUG codes for formyl-methionine (f-Met)

94
Q

What are the stop codons?

A

UGA U Go Away
UAG U Are Gone
UAA U Are Away

These encode for releasing factors.

95
Q

What is an operon

A

the genes that are transcribed (the coding region) plus everything that comes before it that makes transcription happen- the promotor region, regulatory regions, operator region, enhancer region, etc

96
Q

What are transcription factors?

A

Proteins that must bind to the promotor region in order for transcription to take place

97
Q

What are the 4 common structural motifs of transcription factors?

A 
DNA is hard to bind to, so the transcription factors have to have special shapes:
Helix-Loop-Helix
Helix-Turn-Helix
Zinc Finger
Leucine Zipper Protein
98
Q

What are the promotor regions?

A

Places where the RNA polymerase and the transcription factors bind and therefore initiate transcription. Rich in A and T.

There are 2:
-25 TATA box (aka Pribnow, Hogness)
it’s 25 nucleotides before the transcription initation site (start codon)

-75 CAAT box
it’s 75 nucleotides before

99
Q

What is the operator region? Where is it?

A

Located between the -25 promotor and the start site

It’s a place that either binds a repressor (which stops transcription) or binds an inducer (starts transcription).

100
Q

What are response elements?

A

Enhancer regions and repressor (aka silencer) regions- can increase the rate of transcription when bound by protein factors.
can be located close to, far from, or even within the promotor region

101
Q

What is lactose broken down into? And what enz breaks it down?

A

Lactose is broken down into Glucose and Galactose.

Enz is B-galactosidase

102
Q

What product does the lac operon make?

A

It makes B-galactosidase (when necessary). This is the enz that breaks down lactose into glucose and galactose.

103
Q

When would you want the lac operon ON?

A

When you want to make B-galactosidase.
That is, when you want to make it bc a) you have no glucose and need to break down some lactose to get some
AND
b) lactose is there in the first place, waiting to be broken down

104
Q

When would you want the lac operon OFF?

A

If you don’t need B-galactosidase.
That is, if you already have glucose (so no point in breaking down lactose to get some)
and/or
if you don’t have any lactose (no point in making the enz if it can’t actually do anything)

105
Q

Lac operon: when is CAP present? What does it do?

A

When there’s no glucose, CAP is there.
CAP wants to help- it’s pro- making B-galactosidase. It says hey! we need glucose!
(But, if a repressor is there, it can’t do anything)

Glucose inhibits the CAP.

106
Q

Lac operon: when is the lac repressor present? What does it do?

A

Repressor is there when there is no lactose. If there’s no lactose, there’s no point in making the enz that breaks down lactose.

When the lac repressor is bound, the RNA polymerase that makes the DNA can’t bind.

When lactose is there tho, it binds the repressor, so the repressor can’t bind and repress.

107
Q

Lac operon analogy

A

Husband - glucose
Lover- CAP
Kid - repressor
Lactose - school

When the husband (glucose) is present, the lover CAP will not be there. When the husband is absent, the lover will be there.

When there is lactose school, the kid repressor will not be there. But, when there’s no lactose school, the kid will be home.

So, in order for the CAP lover to come over, there needs to be no glucose husband, and there also needs to be lactose, so that the repressor kid will be away at school.

When the glucose husband is gone, the CAP lover is present, and the kid repressor is away at lactose school, it’s ON!

108
Q

What happens if there is a mutation in a gene’s promotor region?

A

(Promotor regions = -25TATA and -75CAAT)

Mutation results in a dramatic decrease in the amt of gene transcribed (so much less protein is made)

109
Q

DNA polymerases vs RNA polymerases in eukaryotes vs prokaryotes.

A

DNA polymerases make DNA
RNA polymerases make RNA

In prokaryotes, there is DNA polymerase III (which elongates the strands) and DNA polymerase I (which excises the RNA primer, degrades it, and fills in the gap with DNA)

In eukaryotes, there are DNA polymerases alpha, beta, gamma, delta, epsilon.

RNA:
In prokaryotes, there is only 1 RNA polymerase (a multisubunit complex) that makes all 3 kinds of RNA

In eukaryotes, there is RNA polymerase I, II, III (for rRNA, mRNA, tRNA respectively)

110
Q

What does RNA polymerase I do?

A

RNA polymerases make RNA.

RNA polym I makes rRNA in eukaryotes

111
Q

What does RNA polymerase II do?

A

RNA polymerases make RNA
RNA polym II makes mRNA in eukaryotes
It also opens DNA at the promotor site

112
Q

What does RNA polymerase III do?

A

RNA polymerases make RNA

RNA polymerase III makes tRNA in eukaryotes

113
Q

What makes RNA in prokaryotes?

A

An RNA polymerase- it is a multisubunit complex that makes all 3 kinds.

114
Q

T/F RNA polymerases have proofreading function

A

False

No proofreading fn, but they can initiate chains.

115
Q

a-amantin

A

Found in death cap mushrooms and inhibits RNA polymerase II

Causes liver failure if eaten.

116
Q

Abx that inhibits prokaryotic RNA polymerase

A

Rifampin

117
Q

RNA processing in eukaryotes

A

Occurs in nucleus, after transcription:

  1. 5’ cap (7-methylguanosine)
  2. 3’ tail, aka polyadenylation (~200 As) AAUAAA is the polyadenylation signal. The poly-A polymerase does not req a template.
  3. Introns are spliced out by the spliceosome

Only RNA that has been processed like this can go out of the nucleus.

118
Q

Why don’t mitochondrial genes have a 5’ cap?

A

RNA processing (adding the 5’ cap) occurs inside the nucleus. Mitochondrial genes are made in the cytoplasm.

119
Q

What is the initial RNA transcript called before processing? What about after?

A

Before: hnRNA (heterogenous nuclear RNA)

After it has been capped and tailed and spliced, it is mRNA, and can go out of the nucleus.

120
Q

Splicing of pre-mRNA (hnRNA)

A

Once of the necessary processings of RNA in eukaryotes.

  1. Primary hnRNA transcript combines w snRNPs and other proteins to form the spliceosome
  2. Lariat (loop) intermediate is made
  3. Lariat is rlsd to remove the intron, the 2 exons are joined
121
Q

How is pre-mRNA splicing affected in pts w lupus?

A

Lupus pts make Ab to the snRNPs of the spliceosome

122
Q

Exons vs Introns

A

Introns are what gets spliced out.
Exons are what stays.

Exons EXit the nucleus (!! not the transcript), which means they are EXpressed.

Introns are INtervening seq’s that stay IN the nucleus (so they are not expressed)

Exons contain the info that codes for protein. Introns are intervening, non-coding segmts of DNA

123
Q

Alternative splicing

A

Taking out different introns (eg 2 introns flanking an exon taken out so the exon is taken out too; for a different protein the exon would have stayed)

Combos of different exons make different proteins for different tsu’s.

Ex: B-thalassemia mutations

124
Q

Where is rRNA sythesized? mRNA? tRNA?

A

rRNA is made in the nucleolus of the nucleus

mRNA and tRNA are made in the nucleoplasm of the nucleus

125
Q

Structure of tRNA

A

75-90 nucleotides
Secondary structure
Cloverleaf form
Anticodon end is opposite the 3’ aminoacyl end.

The 3’ OH end has a CCA and a lot of modified bases. The AA gets covalently bound to the 3’ end of the tRNA (knocks off the OH)
CCA = can carry amino acids

126
Q

What enz adds the amino acid to the tRNA molecule?

A

Aminoacyl tRNA synthetase (using ATP) adds the AA to the 3’OH end of the tRNA.
This is called “charging” the tRNA

There is a different aminoacyl-tRNA for each AA!

The enz also looks at the AA before and after it binds- if it is incorrect, the bond is hydrolyzed.

127
Q

What happens if a tRNA is mischarged?

A

It reads that codon that it should (bc the anti-codon part of the tRNA is fine) but since the wrong AA is attached to the 3’ end of the tRNA, the wrong AA will be inserted into the sequence.

128
Q

What abx prevent attachment of aminoacyl-tRNA?

A

Tetracyclines- they bind the 30S subunit.

129
Q

Where is the anticodon?

A

It’s part of the tRNA.
The codon is part of the mRNA.

anTI is for T-RNA

130
Q

tRNA wobble

A

The base pairing only needs to be right for the first two nucleotide positions of an mRNA codon / tRNA anticodon, so codons that have a different 3rd wobble position can code for the same AA.
This is d/t the degeneracy of the code.
It’s also why silent mutations are silent.

131
Q

Where are ribosomes synthesized?

A

They are made in the nucleus (then txfrd to the cytoplasm in order to do their job)

132
Q

Protein synthesis: initiation

A 
Activated by GTP hydrolysis
Initiation factors (eIFs) help assemble the 40S ribosomal subunit w the initiator tRNA (the one that has the Met and the anti-codon to mRNA's AUG)

eIFs are rlsd once the mRNA and the (other) ribosomal subunit assemble with the complex.

133
Q

Protein synth: elongation

A

Elongation has 3 steps:
1. Aminoacoly-tRNA (that’s a tRNA w an AA attached to it) binds to the A site*
2. Ribosomal RNA aka Peptidyl transferase aka ribozyme catalyzes peptide bond formation bt the new AA (the one on the tRNA in the A site) and the existing AA chain (which is on the tRNA in the P site).
When the peptide bond is made, all of the AA chain is transfered and now hanging off of the tRNA in the A site.
(the tRNA in the P site now has nothing on it)
3. Translocation: the ribosome advances 3 nucleotides toward the 3’ end of the mRNA- this moves the empty tRNA to the E site, and moves the tRNA will the AA chain on it (the “peptidyl RNA”) to the P site, and frees up the A site for the incoming tRNA with one AA on it.

*except the very first one (Met)- it doesn’t bind to the A site

134
Q

What proteins are needed to help with translocation?

A

In prokaryotes: EF-G
In eukaryotes: EF-2

(Translocation is when the ribosome moves 3 nucleotide toward the end of the 3’ mRNA, shifting what’s in the A, P, and E sites)

135
Q

Protein synthesis: termination

A

Completed protein is rlsd from the ribosome thru hydrolysis (req’s one GTP), and dissociates

136
Q

Ribosomal subunits in eukaryotes and prokaryotes

A

Eukaryotes: 40S + 60S = 80S (Even)
PrOkaryotes: 30S + 50S = 70S (Odd)

137
Q

When are ATP and GTP each needed during the process of protein synthesis?

A

ATP = tRNA Activation (charging)- this is when the AA is attached to tRNA, it actually occurs before protein synth occurs

GTP- used for tRNA Gripping (initial assembly) and Going places (translocation step of elongation)

138
Q

A site, P site, E site

A

A site = incoming AminoAcyl tRNA (a tRNA with an AA attached)

P site = accommodates growing Peptide
but note: the peptide chain is transfered to the tRNA that’s in the A site when the peptide bond is made)

E site: holds the Empty tRNA before it Exits

139
Q

What part of protein synthesis do aminoglycosides inhibit?

A

They bind to the 30S subunit (prokaryotes) and therefore inhibit formation of the initiation complex - so they inhibit initiation. They also cause misreading of the mRNA.

140
Q

How does Chloramphenicol inhibit protein synthesis?

A

It inhibits the 50S peptidyl transferase
(so it inhibits the elongation step)

Streptogramins do the same thing.

141
Q

How do macrolides and linezolid inhibit protein synthesis?

A

They bind the 23S (peptidyl transferase, ribozyme) part of the 50S subunit, and therefore block translocation.

142
Q

How does Clindamycin inhibit protein synth?

A

Binds 50S, blocking translocation

143
Q

How do tetracyclines inhibit protein synthesis?

A

Bind to 30S

They inhibit the binding of the Aminoacyl-tRNA to the A site.

144
Q

Trimming (post-translational mods)

A

Removal of N-terminal or C-terminal propeptides from zymogens to create mature proteins

145
Q

Covalent alterations post-translation

A

Phosphorylation

Glycosylation, Hydroxylation on collagen

146
Q

Post-translational proteosomal degradation

A

Attachmt of ubiquitin to defective proteins to tag them for breakdown.
Ubiquitin protein ligase identifies the tagged proteins, and they are sent to the proteosome

147
Q

3 ways to do proteolysis

A

Ubiquitination (sent to proteosome)
Lysosomal degradation
Ca2+-dependent enz degradation

148
Q

Which parts of collagen synthesis happen inside fibroblasts? Outside?

A 
Inside:
Sythesis (RER)
Hydroxylation (ER)
Glycosylation (ER)
Exocytosis

Outside:
Proteolytic processing
Cross-linking

149
Q

Synthesis, hydroxylation, glycosylation, exocytosis of collagen

A

These steps happen inside the fibroblasts:
1. Synthesis (RER) - collagen alpha chains (preprocollagen) are translated in the RER. Usu makes Gly-X-Y (with X and Y being proline, hydroxproline, or hydroxylysine)

  1. Hydroxylation (ER)- hydroxylation of specific proline and lysine residues.
    This step req’s Vit C! (if not, get scurvy)
  2. Glycosylation (ER)- Glycosylation of pro-a-chain lysine residues and the formation of procollagen (triple helix of 3 a chains)
  3. Exocytosis of procollagen into extracelluar space.
150
Q

Which AAs of collagen get hydroxylated?

A

Proline and Lysine

This req’s Vit C

151
Q

Which AA of collagen gets glycosylated?

A

Lysine

152
Q

What is scurvy?

A

Lack of Vit C, which means the proline and lysine of collagen can’t be hydroxylated, so collagen synthesis is impaired.

Collagen synth defect causes swollen gums, bruising, anemia, poor wound healing, tongue petechiae

153
Q

What steps of collagen processing occur after the exocytosis of collagen into the extracellular space (outside of fibroblasts)?

A
  1. Proteolytic processing: cleavage of terminal regions of procollagen. This transforms it into insoluble tropocollagen.
  2. Cross-linking: covalent crosslinking of lysine-hydroxlysine (by enz lysyl oxidase) reinforces the many staggered tropocollagen molecules and makes collagen fibrils.
154
Q

What is Ehlers-Danlos?

A

Faulty collagen synthesis, causing hyperextensible skin, tendency to bleed (easy bruising) and hypermobile joints.

Type III collagen is most freq’ly affected.

Happens when collagen can’t crosslink its lysine and hydoxylysine to make collagen fibrils (lysyl oxidase is the enz)

155
Q

How is collagen synthesis affected in osteogenesis imperfecta?

A

OA is the inability to form pro-collagen from pro-a chains

Have the chains, but can’t make the triple helix with them.

156
Q

Drug that inhibits 50S peptidyltransferase

A

Chloramphenicol and Streptogramins

157
Q

Drug that binds to 50S and blocks translocation

A

Macrolides and Linezolid

158
Q

Drug that binds to 30S, preventing attachment of tRNA

A

Tetracyclines

159
Q

Drug that inhibits prokaryotic DNA polymerase

A

Rifampin

160
Q

Drug that inhibits prokaryotic topoisomerases

A

Fluroquinolones

topois = gyrase

161
Q

Drug that inhibits prokaryotic DHF reductase

A

TMP trimethoprim

for eukaryotes- MTX methotrexate

162
Q

Enz that matches AAs to tRNA

A

Aminoacyl tRNA synthetase

this is called “charging”

* DIT each session (34 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions