[2] Class 6: Nucleotide Structure/ Metabolism Flashcards
DNA 5’ to 3’ gives:
Directionality
Which carbon of the ribose is deoxy in DNA:
2’
What type of bonds form between A-T and C-G
H bonds
DNA helix structure
R handed antiparallel 5’-3’
A-T how may h bonds?
2 h bonds
How many h bonds c-g
3 h bonds
Phosphodiester bond, where is it in dna?
Between 3’ carbon of ribose and 5’ methyl grp on other ribose (below)
Who observed nucleotides in DNA? Who received credit?
Rosalind franklin,
Watson and crick received the prize for it though
How many nucleotides in our genome?
3 billion
How is DNA condensed to fit in our cells?
DNA binding proteins (histones and non-histones) allows for dynamic state between condensation and rapid access for gene expression
Protein+Nuclear DNA=
Chromatin
Phosphate esters of nucleosides
Contain base, sugar and phosphate
Nucleotide
Base + sugar
Nucleoside
WHat type of bond is between the purine/pyramidine base and the ribose sugar?
Beta glycosidic linkage
Big ring:
Small ring:
Small name: purine
Big name: pyrimidine
Purine nucleotide base:
Nucleosides?
Adenine; guanine
Adenosine;guanosine
Pyramidine nucleotide base:
Nucleoside:
Cytosine, Uracil, thymine
Cytidine, uridine, thymidine
Difference in thymine and uracil?
2’ methyl on thymine,
H on uracil
What are the other purines?
Hypoxanthine, inosine, xanthine, xanthosine
How can you go from a nucleotide to a DEOXYnucleotide?
Ribonucleotide reductase
What stimulates and inhibits ribonucleotide reductase?
ATP stimulates ribonucleotide reductase,
dATP nucleotides inhibits ribonucleotide reductase
Bonds of the 3 phosphates in ATP:
Ester bond on the alpha phosphate and 2 anhydride bonds on beta and gamma phosphates
4 specific roles of nucleotides:
ATP, CoA, NAD+, FAD
DNA bonded together is a phosphodiester bond: another name for this is
A covalent bond
DNA measurements:
Length between 1 full turn: 34å 10 basepairs /turn Base pairs are separated by 3.4 å, 36º turn w/ each rotation of a new base pair. 20Å width of DNA
Why is DNA typically in B form: long and slender?
B/c it is typically hydrated in the cell
DNA is more stable w/ more o which base pair?
C-G b/c there are 3 H bonds
Catalyzes the formation of a phosphodiester bridge:
DNA polymerase
RNA of retrovirus is converted to DNA by what enzyme, and subsequent synthesis of DNA strand?
Reverse transcriptase
What enzyme is responsible for cutting long chain RNA/DNA to short oligomers?
(Deoxy)ribonucleases
CLeaves oligomers into nucleotides
Phosphodiesterase
Cleaves nucleotides to nucleosides
Nucleotidase
Cleaves Nucleoside to (deoxy)ribose and base
Nucleosidase
What enzyme can be used to make Uric acid soluble?
URate oxidase makes it into allantoin
Allopurinol inhibits
Xanthine oxidase
Structure of xanthine oxidase
2 FADs
2 Mo atoms
8 Fe atoms
Colchicine helps w/ gout by:
Decreasing movement of granulocytes to affected area
Norma serum uric acid 4-8.6 mg/dL
What is the increased risk of gout measurement?
> 9 mg/dL
Which bases are converted to Glucogenic and ketogenic metabolites
Pyrimidines
5 components that form purines:
5 components of pyrimidines:
CO2, Gln, Asp, N10-formyl-THF
HCO3, Gln, Asp, N5, N10-methylene THF
What is the committed step in purine synthesis?
The formation of phosphoribosyl amine (PRA)
Do you commonly see inosinate in DNA or RNA?
No it is converted to guanosine monophosphate and AMP
2 salvage enzymes in purine:
HGPT and APT
Central constituent of nucleotide metabolism
Synthesized from ribose phosphate and ATP.
Phosphoribosyl pyrophosphate
PRPP
Which ring is synthesized attached to ribose phosphate?
Purine ring
When purines are synthesized onto a ribose sugar…what initially contributes to the ribose sugar?
PRPP
What is the committed step in purine synthesis ?
Formation of PRA
PRPP + glutamine =
PRA
Purine synthesis key step and is inactivated w/ methotrexate:
THF closes the base ring
Methotrexate targets what enzyme that results in inhibiton of DNA replication
Dihydrofolate reductase
It is an analog of folate substrate
TCA intermediates made in purine synthesis:
Fumarate and adenylsuccinate
Synthesis of purine nucleotides is controlled by ______________________ at several sites to balance the productions of purine
feedback regulation
If PRPP is made then inhibited what other 2 molecule would it become?
Histidine and pyrimidine nucleotides
AMP and GMP synthesis is stimulated by:
Synthesis of PRPP, PRA, and GMP and AMP from IMP is
feedback inhibited
Pyramiding is synthesized from:
carbamoyl phosphate
Synthesized from carbamoyl phosphate and aspartate by aspartate-transcarbamoylase
Pyrimidine ring
What is the first and committed step of pyramiding synthesis:
Formation of carbomoyl aspartate and carbamoyl phosphate
What happens before the rxn w/ PRPP in pyramiding synthesis?
It is catalyzed by orate phosphoribosyl transferase
The ring forms
Human hereditary disorder involving the synthesis of pyrimidine nucleotides
Orotic aciduria
Tx: oral uridine
Formed from the ribonucleotides by the reduction of the ribonucleoside diphosphates
Deoxyribonucleotides
Ribonucleotide diphosphate to deoxyribonucleotide by ribonucleotide reductase…what is the H donor for the reduction?
Thioredoxin or glutaredoxin
2 major control points of pyrimidine biosynthesis:
- Carbamoyl phosphate synthetase is hibited by UMP and purines BUT stimulated by PRPP
- Asp transcarbamoylase is feedback inhibited by CTP
DNA is synthesized from dATP,dCTP,dGTP, and dTTP. The [ ] of which is limiting factor?
dTTP
Salvage pathway
Base by self needs to be put back on sugar…this is cheaper then remaking the base
Purine salvage enzymes (2):
Adenine phosphoribosyl-transferase (APRT)
Hypoxanthine guanine phosphoribosyl transferase (HGPRT)
Pyrimidine nucleotide salvage enzymes (2):
Uridine phosphoprylase
Thymidine phosphoprylase
