Nucleotide Structure, Function and Metabolism Flashcards
Nucleosides are what
bases bonded to sugars only
How are nucleosides named
by naming base with -sine or -dine added
What is the structure of nucleotides
sugar, phosphate, and base
how are nucleotides named
by adding -ylate
Why does thyamine not have to have deoxy added to it
because it is not found in RNA
What kind of linkages attach the base to the sugar backbone
Beta-glycosidic linkage
The C-1’ of a sugar is attached by a beta-glycosidic linkage to a ____ of a purine
N-9
The C-1’ of a sugar is attached by a beta-glycosidic linkage to a ____ of a purine
N-1
What is the portion of DNA that codes for a protein
Gene
The phosphodiester bridge has what kind of charge
negative
What is the most common site of phosphate esterification
C-5’
Addition of beta and gamma phosphates are added via
anhydride bonds to each other
In DNA what carbon of the ribose is deoxygenated
The C-2
What affect does the absence of oxygen at C-2’ have
it makes the DNA more resistant to hydrolytic attack, therefore increasing stability
DNA is written and read in what direction
5’-3’
How many hydrogen bonds are between A-T
2
How many hydrogen bonds are between C-G
3
The stacking of bases contributes to the stability of DNA in two ways what are they
Hydrophobic effect
- The hydrophobic bases cluster into the interior whereas the polar backbone faces the exterior
Van der Waals “stacking” forces
- The stacked base attract one antoher
- Although individually are weak when summed together they are strong
DNA exists in 3 forms
A form
B form
Z form
What is the A form of DNA
shorter and wider than B form
base pairs are tilted to the axis and in right handed spiral
only occurs in non-physiological conditions
What is the B form of DNA
Is the most common form b/c it is hydrated like living cellular environments
is longer and narrower than A form
right handed spiral w/base pairs perpendicular to the axis
What is the Z form of DNA
Occurs in segments of DNA that have been methylated
turn about the helical axis in a left handed spiral and the phosphate backbone zigzagged
____ + ____= chromatin
Protien + Nuclear DNA
how many nucleotides are in out genome
3 billion
an incredible amount of ____ is needed to package DNA
condensation
Mitotic chromosomes are condensed _____ times compared to interphase DNA
500 times
DNA binding proteins involved in forming chromosomes are
histones and non-histone chromosomal proteins
Polynucleotides are called
Nucleic acids
Nucleotids contain
a base, a sugar, and a phosphate
Nucleotides are _____ esters of nucleosides
phosphate esters
nucleosides consist of
a base and a sugar
Sugars are attached to a base via a ________
N-glycosidic linkage (in DNA it is a beta-glycosidic linkage because it is above the plane)
The C-1 of a sugar is attached by beta-linkage to what location of a purine
N-9
The C-1 of a sugar is attached by beta-linkage to what location of a pyrimidine
N-1
What is the purpose of the phosphodiester bridge having a negative charge
it repels nucleophilic species (like hydroxide ions) thus makes them less susceptible to hydrolytic attack than other esters
What is the most common site of phosphate esterification
C-5’
Phosphates are attached to a sugar via a
ester bond
phosphates are attached to each other via a
anhydride bond
DNA is deoxygenated at what carbon
C-2’
What is the purpose of the deoxygenation of DNA at C-2’
it makes DNA more resistant to hydrolytic attack and thus more stable
What direction is DNA written
5’-3’
how far apart are adjacent bases on DNA double helix
3.4 angstroms
The bases on DNA double helix are located
nearly perpendicular to the helix axis
The helical structure of DNA repeats every
10 bases or 34 angstroms
each base of the DNA alpha helix contributes ____ degrees of turn, so ____ bases per turn
36 degrees, so 10 bases per turn
The sugar backbone is located on the _____ of the DNA double helix
outside
The bases are located on the _____ side of the DNA double helix
inside
The ratio of purines and pyrimidines is
1:1
The ratio of what varies considerably form species
A-G
DNA with high ___ content is more stable
GC
what does ribonucleotide reductase due to a nucleotide diphosphate (note that NADPH is required)
It makes 2’- deoxynucleotide diphosphate
ATP does what to ribonucleotide reductase
activates it
dATP does what to ribonucleotide reductase
it inhibits it
What converts long strand RNA to short RNA
Ribonucleases
What converts long DNA chain to DNA oligomer or short chain DNA
Deoxyribonucleases
What does cleaves the phosphodiester bond of DNA and RNA oligomers to form monophosphates
Phosphodiesterase
What cleaves the phosphate off a nucleotide to form a nucleoside
Nucleotidase
what cleaves the base of a nucleoside to form a base and separate ribose/deoxyribose
nucleosidase
Allopurinol inhibits what specific enzyme
Xanthine oxidase
allopurinaol inhibits xanthine oxidase and therefore does not allow ____ to be converted to ____ and ____ to be converted to _____
hypoxanthine to be converted to xanthine and xanthine to uric acid
What does urate oxidase do
it is an enzyme not present in humans that converts uric acid to a more water soluble form Allantoin
Plays an important role in adenosine homeostasis and modulates signaling by extracellular adenosine and so contributes indirectly to signaling
Adenosine Deaminase (ADA)
The overproduction of Adenosine Deaminase (ADA) in erythrocytes causes
hemolytic anemia. It is rare.
increased degradation of adenosine depletes adenine nucleotide pool and triggers premature destruction of RBCs.
What is the final product of purine catabolism
Uric Acid
Underproduction of Adenosine Deaminase ADA is associated with
The second most common form of severe combined immunodeficiency (SCID)
What catalyzes the oxidation of hypoxanthine to xanthine and xanthine to uric acid
Xanthine Oxidase
The inhibition of what enzyme by allopurinol is a major target for the treatment of Gout
Xanthine oxidase
What is the structure of xanthine oxidase
2 Flavin adenine dinucleotides (FADs), 2 Mo atoms, and 8 Fe atoms per molecule of enzyme
Deficiency of ADA leads to
SCID, high amounts of adenosine which is then converted into dATP, high levels of which block the synthesis of all other dNDPs and dNTPs,
Impaired DNA synthesis and compromised immune system
What is the most commonly affected area for GOUT
Big toe (metatarsal pharangeal joint)
High uric acid levels in the blood, leading to sodium urate crystals precipitate in the synovial fluid joints
Gout
What is primary hyperuricemia
overproduction of uric acid
What is secondary hyperuricemia
under-excretion of uric acid
What is the level for hyperuricemia
uric acid concentrations exceed plasma solubility (about 7 mg/dL)
What kind of diet increases the risk of gout
Rich in Purines (beans, lentils, spinach) together with meat, seafood, and alcohol
What are some treatments for GOUT
colchicine- decrease movement of granulocytes to the affected area
Allopurinol- inhibits xanthine oxidase to form the more soluble hypoxanthine
urate oxidase- catalyzes uric acid to allantoin, which is more water soluble
What is the normal serum uric acid level in adult males
4-8.6 mg/dL
What is the normal serum uric acid level in adult females
3.0-5.9 mg/dL
Serum urate levels greater than
> 9 mg/dL means an increased risk of gout
Thymine derivatives final product (s) of catabolism
MethylmalonylCoA and Succinyl CoA
Both are glucogenic
Cytosine and Uracil derivatives after catabolism
Malonyl CoA, which is ketogenic
Malonyl CoA, Methylmalonyl CoA, and succinyl CoA are all ____ soluble
water soluble
What is the source of rings atoms for Purine bases
CO2, Gln, Gly, Asp, N^10-formyl THF
What is the source of the rings atoms for prymidine bases
HCO3-, Gln, Asp, N^5, N^10- methylene THF
What is the committed step in the purine synthesis
formation of the phosphoribosyl amine (PRA)
How many phases are there to De Novo synthesis
4
Where does the alpha-D- ribose 5-phosphate from phase I of De novo purine synthesis come from
Pentose phosphate pathway
What is phase I of the De Novo synthesis of purines
Ribose-5P activation
What is the activated form of Ribose-5P
5-phospho-alpha-D-ribosyl-1- pyrophosphate (PRPP)
note that it has 3 phosphates attached, 1 at C5’ and 2 at C1’
What is phase II of De Novo Purine synthesis
conversion of PRPP to PRA (phosphoribosylamine) (note that this is the converted step)
Methotrexate blocks what phase of de novo purine synthesis
Phase III: construct IMP ring
How many steps is phase III of de novo purine synthesis
9 steps
What is phase IV of de novo purine synthesis
Convert IMP to adenosine and guanosine (deoxy) nucleotides
Ribonuclease reductase is an enzyme that catalyzes
a ribose to a deoxyribose
GMP and AMP inhibit what phases of de novo purine synthesis
Phase I,II, IV
IMP inhibits what phases of de novo purine synthesis
Phase I and II
Phosphates promote what phase of de novo purine synthesis
Phase I
PRPP promotes what phase of de novo purine synthesis
Phase II
Hypoxanthine ribose phosphate is the same thing as
Inosine monophosphate (IMP)
What is the product of phase III of de novo purine synthesis
Inosine monophosphate (IMP)
what are the two salvage enzymes of purine biosynthesis
Hypoxanthine guanine phosphoribosyl transferase
Adenine phosphoribosyl transferase
what is the specific target of methotrexate
dihydrofolate reductase that converts in the liver
methotrexate binds dihydrofolate ___ times more tighlty than the forming IMP
100
AMP synthesis is stimulated by
GTP
GMP synthesis is stimulated by
ATP
how many phases is the de novo synthesis of pyrimidine nucleotides
3
What is phase I of pyrimidine synthesis
fabrication of orotate ring
What is phase II of De Novo synthesis of Pyrimidines
Attach PRPP to form UMP
What is phase III of de novo synthesis of pyrimidines
Convert UMP to uridine, cytosine and thymine (deoxy) nucleotides
The pyrimidine ring is sythesized from carbamoyl phosphate and aspartate by
aspartate-transcarbamoylase
What is the function of carbamoyl phosphate synthetase II in pyrymidine synthesis
it catalyzes the formation of carbamoyl phosphate from Gln, bicarbonate, and 2ATP
Why is uridine phosphorylase said to be versatile
It is able to convert Uridine/deoxyuridine and Deoxythymidine to uracil and thymine respectively
In purine de novo synthesis Methotrexate inhibits what
it inhibits dihydrofolate reductase that converts in the liver that converts dihydrofolate to tetrahydrofolate, which is then used to form the ring and thus IMP
What does 5-fluorouracil inhibit
it inhibits thymidylate synthase, which with Tetrahydrofolate converts dUMP to dTMP
Orotic aciduria is a deficiency in what enzyme
UMP synthase
What is orotic aciduria treated with
oral uridine
The deoxyribonucleotides are formed from the ribonucleotides by the reduction of the
ribonucleoside diphosphates
What is the immediate hydrogen donor for the reduction of ribonucleoside diphosphate is reduced
thioredoxin or glutaredoxin
