lecture 19

during nucleotide metabolism, _ is removed during break down

nitrogen

nucleotides _ give us energy, because don’t want to breakdown DNA to get energy

do not

the constituents of nucleic acids are:

base, sugar, phosphodiester linkage

the base of nucleic acids are _ bases and can be either _ or _

nitrogenous, purine, pyrimidine

the constituents of nucleic acids:

the sugar can either be _ or _

ribose, deoxyribose

a purine has _ cyclic rings

2

a _ has 2 cyclic rings

purine

a _ has 1 cyclic ring

pyrimidine

a pyrimidine has _ cyclic ring

1

_ is the sugar for RNA and has a hydroxyl (OH) group on the 2’ carbon

ribose

ribose is the sugar for _ and has a hydroxyl (OH) group on the 2’ carbon

RNA

ribose is the sugar for RNA and has a _ group on the 2’ carbon

hydroxyl (OH)

ribose is the sugar for RNA and has a hydroxyl (OH) group on the _ carbon

2’

_ is the sugar for DNA and has a hydrogen (H) on the 2’ carbon

deoxyribose

deoxyribose is the sugar for _ and has a hydrogen (H) on the 2’ carbon

DNA

deoxyribose is the sugar for DNA and has a _ on the 2’ carbon

hydrogen (H)

deoxyribose is the sugar for DNA and has a hydrogen (H) on the _ carbon

2’

chemical structures of nucleotides:

5’-ribonucleotide:

phosphate group on the _ carbon

OH group on the _ carbon

nitrogenous base (purine or pyrimidine) on _ carbon

5’, 2’, 1’

chemical structures of nucleotides:

_:

phosphate group on the 5’ carbon

OH group on the 2’ carbon

nitrogenous base (purine or pyrimidine) on 1’ carbon

5’-ribonucleotide

chemical structures of nucleotides:

_:

phosphate group on the 3’ carbon

H on the 2’ carbon

nitrogenous base (purine and pyrimidine) on 1’ carbon

3’-deoxynucleotide

chemical structures of nucleotides:

3’-deoxynucleotide:

phosphate group on the _ carbon

H on the _ carbon

nitrogenous base (purine and pyrimidine) on _ carbon

3’, 2’, 1;

pyrimidines have a _ ring cyclic structure and includes _

1, CUT

purines have a _ ring cyclic structure and includes _

2, AG

phosphodiester bond forms between the _ of the sugar of nucleic acids (5’ on ribonucleotide, 3’ on deoxynucleotide)

phosphate groups

a _ is composed of the base plus sugar

nucleoside

a _ is composed of the base, sugar, and phosphate group - come together using phosphodiester linkage

nucleotide

uric acid is a _

purine

how do scientists know where the molecules that make up purines come from?

take derivatives and label with _ or other non _ materials, run through the mass spec, determine where labeled molecule is in purine structure

radioactive

the atomic origins of purines shows that if you don’t have the molecules running through _, you cannot produce purines, DNA or RNA, or replicate

metabolic pathways

the components that make up purines include:

_, _, _, _, and _

aspartate amine, bicarbonate (HCO3-), glycine, formate, glutamine amide

an amide is composed of 2 _ chains (glutamine amide)

nitrogen

the initially synthesized purine derivative is _. from here, can make other purines

inosine monophosphate (IMP)

the initially synthesized purine derivative inosine monophosphate (IMP) is made up of _, _, and _

phosphate group, sugar, hypoxanthine base (nitrogenous base)

in de novo biosynthesis of IMP, _ total high energy molecules are used

7

de novo biosynthesis of IMP involves _ reactions

11

the first two high energy molecules are used during reaction _ of de novo biosynthesis of IMP

1

the third high energy molecule is used in reaction _ of de novo biosynthesis of IMP

3

the fourth high energy molecule is used in reaction _ of de novo biosynthesis of IMP

5

the fifth high energy molecule is used in reaction _ of de novo biosynthesis of IMP

6

the sixth high energy molecule is used in reaction _ of de novo biosynthesis of IMP

7

the seventh high energy molecule is used in reaction _ of de novo biosynthesis of IMP

8

making nucleotides and nucleic acids is a very _ intensive process - the body only does it if it has enough to spend. need an abundance of resources to make more genetic material for replication

energy

the de novo biosynthesis of IMP begins with a _ molecule, which is made from _ coming off of _

ribose-5-phosphate, PPP, glycolysis

in reaction 1 of de novo biosynthesis of IMP, _ are added onto the future purine backbone

2 phosphates from ATP

in reaction 2 of de novo biosynthesis of IMP, _ are removed and _ is added onto the future purine backbone

2 phosphate groups, glutamine amide (NH2)

in reaction 3 of de novo biosynthesis of IMP, _ is added onto the future purine backbone

glycine molecule

in reaction 5 of de novo biosynthesis of IMP, the second _ is incorporated into the future purine backbone

glutamine

in reaction 7 of de novo biosynthesis of IMP, _ is incorporated into the future purine backbone

C from bicarbonate

in reaction 8 of de novo biosynthesis of IMP, _ is incorporated into the future purine backbone

aspartate amine

in reaction 9 of de novo biosynthesis of IMP, _ is lost from the future purine backbone, but _ stays

fumarate, nitrogen group

in reaction 11 of de novo biosynthesis of IMP, _ is released

water

1 IMP can be converted into either _ or _

AMP, GMP

it takes the 7 high energy molecules of IMP biosynthesis plus an additional _ high energy molecule to create AMP

1

it takes the 7 high energy molecules of IMP biosynthesis plus an additional _ high energy molecules to create GMP

2

after IMP conversion into _ or _, purines can then attach onto other nucleotides and start being a part of RNA or DNA

AMP, GMP

immunosuppressant inhibits _

IMP dehydrogenase

_ inhibits IMP dehydrogenase

immunosuppresant

_ is an immunosuppressant that inhibits IMP dehydrogenase

mycophenolic acid

_ directly impact replication processes, therefor affecting overall growth

immunosuppressants

an immunosuppressed individual may have similar amounts of IMP like a normal individual, but the body prioritizes making A over G because of suppressing the enzyme that makes G, which is _. this leads to higher rates of mutation because not enough GMPs, so replication processes tend to stall out

IMP dehydrogenase

overall, purine biosynthesis is activated by high levels of _ and inhibited by high levels of _

substrate, product

control of purine biosynthesis:

_ activates the PRPP to 5-phosphoribosylamine step (catalyzed by amidophosphoribosyl transferase)

PRPP

control of purine biosynthesis:

high levels of _, _, and _, inhibit the PRPP to 5-phosphoribosylamine step (catalyzed by amidophosphoribosyl transferase)

AMP, ADP, ATP

control of purine biosynthesis:

high levels of _ inhibit the IMP to adenylosuccinate step catalyzed by adenylosuccinate synthetase

AMP

control of purine biosynthesis:

high levels of _ inhibit the ribose-5-phosphate to PRPP step catalyzed by ribose phosphate pyrophosphokinase

ADP

control of purine biosynthesis:

high levels of _ inhibit the ribose-5-phosphate to PRPP step catalyzed by ribose phosphate pyrophosphokinase

GDP

control of purine biosynthesis:

high levels of _, _, _and _ inhibit the PRPP to 5-phosphoribosylamine step catalyzed by amidophosphoribosyl transferase

XMP, GMP, GDP, GTP

control of purine biosynthesis:

high levels of _ inhibit the IMP to XMP step catalyzed by IMP dehydrogenase

GMP

_ is synthesized through the assembly of a purine base on ribose-5-phosphate

IMP

IMP is synthesized through the assembly of a _ base on _

purine, ribose-5-phosphate

_ convert IMP-derived AMP and GMP to ATP and GTP

kinases

kinases convert IMP-derived _ and _ to ATP and GTP

AMP, GMP

kinases convert IMP-derived AMP and GMP to _ and _

ATP, GTP

_ is regulated by feedback inhibition and a feedforward activation

purine nucleotide synthesis

purine nucleotide synthesis is regulated by _ and a _

feedback inhibition, feedforward activation

_ reactions convert purines to their nucleotide forms

salvage

salvage reactions convert purines to their _ forms

nucleotide

the atomic origins of pyrimidines are _ complicated than purines

less

the atomic origins of pyrimidines include:

_, _, and _

glutamine amide, bicarbonate (HCO3-), aspartate

de novo synthesis of UMP involves _ reactions

6

_ of pyrimidine biosynthesis is the equivalent of IMP of purine biosynthesis

UMP

de novo synthesis of UMP uses _ high energy bonds

4

the first set of two high energy bonds are used during reaction _ of UMP synthesis

1

the second set of two high energy bonds are used during reaction _ of UMP synthesis

5

reaction 1 of de novo synthesis of UMP adds the _ and the _ to the pyrimidine backbone

glutamine amide, bicarbonate

reaction 2 of de novo synthesis of UMP adds the _ to the pyrimidine backbone

aspartate

the 4 high energy bonds plus an additional _ ATP molecule is required to create CTP from UTP

1

regulation of _ biosynthesis is different between prokaryotes and eukaryotes/animals

pyrimidine

in E. coli/prokaryote regulation of pyrimidine biosynthesis:

_ activates the carbamoyl phosphate to carbamoyl aspartate step catalyzed by ATCase

ATP

in E. coli/prokaryote regulation of pyrimidine biosynthesis:

_ inhibits the carbamoyl phosphate to carbamoyl aspartate step catalyzed by ATCase

CTP

only _ inhibits the carbamoyl phosphate to carbamoyl aspartate step catalyzed by ATCase because the reduced genome size of prokaryotes allows similar genes to work together - genes next to each other are controlled by a single promoter

CTP

in animal/eukaryote regulation of pyrimidine biosynthesis:

_ and _ activate the HCO3-+glutamine+ATP to carbamoyl phosphate step catalyzed by carbamoyl phosphate synthetase II

ATP, PRPP

in animal/eukaryote regulation of pyrimidine biosynthesis:

_ and _ inhibit the HCO3-+glutamine+ATP to carbamoyl phosphate step catalyzed by carbamoyl phosphate synthetase II

UDP, UTP

in animal/eukaryote regulation of pyrimidine biosynthesis:

_ inhibits the OMP to UMP step catalyzed by OMP decarboxylase

UMP

_ activates both purine and pyrimidine biosynthesis in higher animals

PRPP

in animals/eukaryotes, almost all genes have separate promoters and regulators, which is why there are _ areas for regulation in pyrimidine biosynthesis than there are for prokaryotes/E. coli

more

_ is synthesized as a pyrimidine base to which ribose-5-phosphate is added

UMP

UMP is synthesized as a _ base to which ribose-5-phosphate is added

pyrimidine

UMP is synthesized as a pyrimidine base to which _ is added

ribose-5-phosphate

CTP and UTP are derived from _

UMP