804 BCH Week 2 - DNA, RNA, Transcription

R5P and ATP

PRPP is a molecule produced from ___ and ___

IMP

___ is the first purine nucleotide synthesized

PRPP, amino acids, folate, ATP

What 4 things are used to synthesize purines

IMP

AMP and GMP are synthesized from ___

reciprocally

The biosynthesis of ATP and GTP are ____ regulated by the concentration of the other

ATP and GTP

Kinases convert AMP and GMP to ___

feedback inhibition and feedforward activation

Purine synthesis is regulated by ___ and ___ to maintain concentration of purines

Branchpoint

___ control regulation is used to maintain a balance of each purine

pyrimidine biosynthesis

The photos are "ingredients" for

developmental delay, seizures, ataxia, language deficits, mental retardation, anemia, hypouricosuria, high levels of uracil and thymine in urine

What are some disorders of pyrimidine metabolism

pyrimidine base on PRPP

pyrimidine nucleotides are synthesized by placing an assembled ____

OMP

___ is the first pyrimidine nucleotide synthesized

UTP, glutamine, ATP, H20

UMP synthesized from OMP & CTP is made from what 4 things

UTP

Kinases convert UMP to ___

substrate (PRPP), energy levels (ATP; activates), and product levels (UDP, UTP; inhibits)

Pyrimidine synthesis is regulated by what 3 things

2' deoxy-forms

thymine nucleotides are only synthesized as ___

Synthesized

TMP, TDP, TTP are not ___

ATP, PRPP

Carbamoyl phosphate synthetase II is activated by ___

UTP, UDP

Carbamoyl phosphate synthetase II is inhibited by ___

dADP, dGDP, dCDP, dUDP

Ribonucleotide Reductase (RR): one enzyme produces 2'-deoxyribonucleoside diphosphate - what are 4 examples

2' hydroxyl

RR removes what

1- catalyzed by ribonucleotide reductase (RR)

2- NDP is reduced (2' position) to form dNDP

3- NADPH provides reducing power via thioredoxin (protein intermediate)

what are the 3 steps of synthesis of 2'-deoxy-ribonucleotides for DNA

glutaredoxin

___ can be used in place of thioredoxin in synthesis of 2'-deoxy-ribonucleotides for DNA

produce correct ratios of 4 dNDPs

what is the goal of ribonuleotide reductase enzyme

dTTP from dUMP

thymidylate synthase and thymidine kinase together make ____

add a methyl group to dUMP

How is deoxythymidine produced

thymidylate synthase

What is is deoxythymidine production catalyzed by

dihydrofolate reductase (key enzyme in biosynthetic production of dTMP)

N5, N10 - methylene-tetrahydrofolate must be regenerated by ___

reuse of bases

what is nucleotide salvage

catabolizes bases

what is nucleotide degradation

cell turnover, dietary nucleic acids, pathogens

3 sources of nucleotide salvage and degradation

intestine; nucleosides and nucleoside phosphorylases

nucleosides are absorbed through the ___ OR further degraded by ___

uric acid

in nucleotide degradation, purines are broken down to ___

removing base from nucleotides, then sugars

in purine degradation, degradation proceeds by ___

adenosine deaminase

in purine degradation, deficiency of ____ causes SCIDS

HGPRT (HPRT)

in purine salvage, bases are added to PRPP by ___

Lesch-Nyhan syndrome

in purine salvage, deficiency of HGPRT (HPRT) causes ___

corresponding nucleotides

in purine salvage, free purines are reconverted to ___

CoA

in nucleotide degradation, pyrimidines are converted to ___ derivates for catabolism

an excess of uric acid

gout is ___

allopurinol

____ treats gout by irreversibly inhibiting xanthine oxidase

urea

in pyrimidine degradation or salvage, pyrimidines degrade to ___

cytotoxic (kills dividing cells); targeted (kills cancer cells by targeting unique molecular properties)

Chemotherapy is ___ and ___

antimetabolite drugs

The following drugs are what

antimetabolite used to treat cancer

5-fluorouracil is __

thymidylate synthase

5FU (5F-uridine) inhibits ___

5-FU metabolism

the following is a photo of

false; multi-drug cocktails are used to treat cancer

true or false: only one drug at a time is used to treat cancer

apoptosis and DNA repair

two common results from DNA damage are

therapeutic index greater than 1

what therapeutic index value for a drug is best for killing cancer cells?

INCREASED DNA REPAIR, decreased drug uptake, increased drug export, increased drug detoxification, reduced activation of pro-drug

what are some chemoresistance mechanisms (DNA repair)

(the first one being the most important to remember)

DNA

this photo shows common damaging agents of ___

linear energy transfer

x-rays have low ___ that may cause ionizing radiation DNA damage

FALSE - a non-damaged chromosome CAN be used to repairs its double strand DNA damaged homologous chromosome

true or false: a non-damaged chromosome cannot be used to repairs its double strand DNA damaged homologous chromosome

BRCA 1 or BRCA 2

inherited mutations in what genes give an increased risk of breast/ovarian cancer

single and double strand

ionizing radiation can cause ___ break repair

regulated DNA-dependent biochemical process that results in synthesis of RNA

transcription

regulated RNA-dependent biochemical process that results in the synthesis of amino acid sequences or polypeptides

translation

the synthesis of amino acid sequences or polypeptides

translation results in __

RNA synthesis done by rewriting information contained in DNA

Transcription is essentially

RNA polymerases

RNA synthesis is catalyzed by DNA dependent

initiation, elongation, termination

3 key steps in transcription

TRUE - there is no proofreading or repair

true or false: RNA polymerases do not edit DNA

FALSE - no primer required to start synthesis

true or false: there is a primer required to start synthesis of RNA

the gene promoter

the starting site of transcription Is controlled by ___

One - single RNA polymerase

bacteria have how many RNA polymerases

3 -

know RNA Polymerase II - mRNA, snRNA, miRNA

eukaryotes have how many RNA polymerases

located at 5' of and approximately 10 bases from the transcription start site (TSS)

Pribnow box

initiation

RNAP sigma factor has a major function in transcription ___

5' to 3'

RNA synthesis occurs in ___ direction

eukaryotic gene promoter

RNA pol II is a ___ of transcription

50 - 60%

what percent of genes gave an upstream TATA box element at -30 to -100

mRNAs

RNA poll II is required for synthesis of

basal transcription factors (common to all genes transcribed by pol II)

TATA-binding protein binds, followed by other proteins called ___

phosphorylated

Once transcription complex is assembled, RNAP II is ____, beginning elongation

removing introns and joining exons to make mature mRNA

Define RNA splicing

site-specific cleavage and ligation

spliceosome accomplishes

snRNAs

spliceosomes contain

1-cleavage by endonuclease 2- addition of polyA by polyadenylate polymerase

polyA is added at consensus sequence in 2 steps:

AAUAAA

consensus sequence

immediately proximal to RNA transcription start site

gene promoter

increased diversity in proteins produced

alternative splicing allows for

translate information stored in DNA into proteins

the genetic code is used to

evolutionarily conserved

the genetic code is ___

genes that perform certain functions in lower animals have been maintained even in the human DNA script, though sometimes the genes have been modified for more complex functions.

what does "evolutionarily conserved" mean

3

each mRNA has how many potential reading frames

a different protein

each mRNA reading frame produces

always methionine

first amino acid in open reading frame (ORF) is

linearly; N; C

polypeptide chains are assembled ___ from ___ terminus to ___ terminus

multiple codons result in addition of the same amino acid --> a single tRA must be capable of recognizing multiple codons

what does it mean that the genetic code is degenerate

anticodon

tRNAs base pair with mRNA using a

32

how many tRNAs are there

recognize more than one codon in mRNA

because there are only 32 anticodons and 61 codons, tRNA anticodons must

wobble base pairing in 3rd position of the codon

why is it possible for anticodons to recognize more than one codon

1-activation of amino acids

2-initiation

3-elongation

4-termination

5-folding and processing of protein

5 steps of translation protein synthesis

aminoacyl tRNA synthetase.

this reaction is catalyzed by

1-position next tRNA

2-form peptide bond between amino acids

3-translocate ribosome

3 steps of elongation

end of polypeptide synthesis and release of new synthesized protein

termination

FALSE - protein synthesis on ribosomes is similar

(small differences exist and are important in use of antibiotics)

true or false: the process of protein synthesis on ribosomes is different between prokaryotes and eukaryotes

upstream of AUG, initiates translation by aligning codon over the P site

shine-dalgarno sequence