Nucleic Acids (Lecture 30)

Question 1

after the first 2 steps of purine de novo synthesis, what occurs? (steps 3-6)

Answer 1

glycine and ATP is added to beta 5 phosphoribosylamine to synthesize GAR

then a carbon from N10 formyl-THF is added via the enzyme GAR transformylase

another nitrogen is added, which is donated from the side chain of glutamine (release glutamate) to form FGAM

cyclization occurs to form 5-aminoimidizole ribotidde (AIR)

Question 2

what are steps 7-10 of purine de novo synthesis?

Answer 2

addition of HCO3- and ATP to AIR. to form CAIR (via AIR carboxylase)

addition of aspartate (donates N form backbone) and ATP via SACAIR synthase to form SACAIR

adenylosuccinate cleaves/releases fumarate from the compound to form AICAIR

AICAR transformylase adds a carbon from N10 formyl THF to form FAIRCAR

Question 3

what is ZMP and how does it work?

Answer 3

ZMP is a drug given in its nucleoside form, acadesine.

it functions by binding to AMP dependent protein kinase to activate it, and causes an increase in body mass

Question 4

how is IMP synthesized?

Answer 4

FAIRCAR is transformed into IMP via a cyclization performed by IMP cyclohydrase

Question 5

which intermediate is the branch point for the synthesis of GMP or AMP?

Answer 5

IMP as for its a purine base intermediate

Question 6

how do we synthesize AMP?

Answer 6

Aspartate and GTP is added to IMP via adenylosuccinate synthase to form adenylosuccinate

adenylosuccinate lyase will then cleave a fumarate to form AMP

Question 7

what is the difference. between IMP and ATP

Answer 7

replace extra cyclic oxygen with a Nitrogen

Question 8

how do we synthesize GMP?

Answer 8

add NAD+ and H2O to IMP via IMP dehydrogenase (oxidation reaction) to add an extra cyclic oxygen. this forms XMP

Glutamine and ATP are then added to XMP via GMP synthase to form GMP

Question 9

when there’s an abidance of ATP, which nucleotide synthesis is favoured?

Answer 9

GMP, since ATP is required in this process

Question 10

when there’s an abidance of GTP, which nucleotide synthesis is favoured?

Answer 10

AMP, since GTP is required in this process

Question 11

diphosphate are created from monophosphates via ______ kinases

Answer 11

base specific kinases

Question 12

which kinase is used to convert AMP + ATP to 2ADP?

Answer 12

adenylate kinase

Question 13

which kinase is used to convert UMP + UTP to 2UDP?

Answer 13

uridylate kinase

Question 14

triphosphosphates are synthesized via ____ kinase.

Answer 14

non-specific kinase

nucleoside diphsopahte kinase

Question 15

when do the kinases run forward/backward

Answer 15

depending on the deltas G (usually at equilibrium) and mainly the concentrations of reactants

Question 16

there's roughly  \_\_\_ more: 
RNA than DNA
NTP than dNTP
NTP than NDP
NDP than NMP

Answer 16

7 TIMES!

Question 17

how is purine synthesis regulated?

Answer 17

product feedback inhibition by nucleotides

it is regulated at the first 2 steps

Question 18

what is the feedforward /activation of purine synthesis?

Answer 18

PRPP positively regulates the second step (increase concentration of PRPP causes increase in purine synthesis)

Question 19

what are sulfonamindes used for and what do they do?

Answer 19

antibiotics due to their similarity to p-aminobenzoic acid. these drugs inhibit the synthesis of folate

Question 20

name the groups carried and the THF derivatives of the methanol oxidation level:

Answer 20

group carried:
methyl

THF derivatives:
N5-methyl-THF

Question 21

name the groups carried and the THF derivatives of the Formaldehyde oxidation level:

Answer 21

group carried:
methylene

THF derivative:
N5,N10-Methylene-THF

Question 22

name the groups carried and the THF derivatives of the formate oxidation level:

Answer 22

groups carried:
formyl
formimino
methenyl

THF derivatives:
N5-formyl-THF
N10-formyl-THF
N5-formimino-THF
N5,N10-methenyl-THF