Week 4: Nucleotide Metabolism I

Question 1

How do nucleotides support cellular metabolism, signal transduction, and play a role in pathogenesis?

Answer 1

Metabolism: (1) Form carriers of chemical energy (ATP, GTP, etc)

(2) Act as cofactors in metabolic pathways, e.g. NAD+ and FAD+ (electron carriers)
(3) act as substrates for DNA/RNA synthesis
(4) are components of biosynthetic intermediates, like UDP-glucose

Signaling: (1) form signal molecules, like the second messenger molecule cAMP

Pathogenesis: (1) Covalently modify enzymes, as in ADP-ribosylation of G proteins completed by cholera toxin of Vibrio cholerae

Question 2

What is the difference between the de novo and salvage pathways of nucleotide biosynthesis?

Answer 2

The de novo pathway involves the formation of nucleotides from scratch, using ribose phosphate, amino acids, CO2 and ammonia.

The salvage pathway involves recycling free bases or nucleosides available from the breakdown of nucleic acids.

Question 3

SCID (Severe Combined Immunodeficiency Disorder) can be caused by a deficiency in ________________.

Answer 3

Adenosine deaminase

Question 4

Lesch-Nyhan Syndrome can be caused by deficiencies in ___________-_________ ____________________. Its symptoms include…

Answer 4

Hypoxanthine-guanine phosphoribosyltransferase

…intellectual disability, spacticity, irregular and jerky movements, self-mutilation, hyperuricemia

Question 5

Gout can be caused by a deficiency in _____________, and symptoms include…

Answer 5

Uricase

…high levels of uric acid, which are not broken down improperly and collect in connective tissue. There, they cause inflammation and joint pain.

Question 6

Ribose-5-phosphate forms PRPP (5-phosphorobosyl pyrophosphate) via the ______________ enzyme. It is inhibited by _______.

Answer 6

ribos phosphate pyrophosphokinase (PRPP synthase)

inhibited by ADP.

Question 7

PRPP forms 5-phosphoribosylamine via the _________________ enzyme, and is inhibited by _________.

Answer 7

Glutamine-PRPP amidotransferase.

Inhibited by AMP, GMP, and IMP.

Question 8

5-phosphoribosylamine is converted to IMP via __ steps. We remember the intermediates via…

Answer 8

Ribose-5-phosphate –> PRPP, then…

Royal (Ribose-5-P)

Peter (5-phosphoribosyl-1-pyrophosphate, PRPP)

Pan (5-phospho-B-D-ribosylamine, PRA)

Got (Glycinamide ribonucleotide, GAR)

Fudges (Formylglycinamide ribonucleotide, FGAR)

And (5-Aminoimidazole ribonucleotide, AIR)

Cadbury (Carboxyaminoimidazole ribonucleotide, CAIR)

Stolen (N-Succinylo-5-amidoiminazole-4–carboxyamide ribonucleotide, SAICAR)

All (5-Amidoiminazole-4-carboxyamide ribonucleotide, AICAR)

From (Formyl-5-amidoiminazole-4-carboxyamide ribonucleotide, (FAICAR)

India (Inosinate monophosphate, IMP)

Question 9

IMP is made into AMP using the enzymes (1)__________ and (2)__________, the addition of (3)_________ and removal of (4)___________, and a molecule of (5)______ to drive the reaction.

Answer 9

“Ass Fumes” Pathway: (1) adenylosuccinate synthetase

(2) adenylosuccinate lyase
(3) Aspartate
(4) Fumarate
(5) GTP

Question 10

IMP is converted to GMP using the enzymes (1) ____________ and (2) ________________, the addition of (3)______________ and (4)_____________, and the use of a molecule of (5)___________ to drive the reaction.

Answer 10

The “IMP CHIMP” Pathway: (1) IMP dehydrogenase

(2) XMP-glutamine amidotransferase
(3) water
(4) Glycine
(5) ATP

Question 11

G Pathway: IMP is first converted into (1)_____ via the enzyme (2)___________, which is inhibited by (3)__________.

Then, that molecule is converted into (4)___________ by the enzyme (5)_____________.

Answer 11

(1) XMP
(2) IMP dehydrogenase
(3) GMP
(4) GMP
(5) XMP-glutamine amidotransferase

Question 12

A Pathway: IMP is converted into (1)__________ via the enzyme (2) _______________. Then, that molecule is converted into (3)____________ by the enzyme (4)_________. The first enzyme is inhibited by (5)____.

Answer 12

(1) Adenylosuccinate
(2) Adenylosuccinate synthetase
(3) AMP
(4) Adenylosuccinate lyase
(5) AMP

Question 13

What substrates do both bacterial and animal pyrimidine synthesis begin with?

Answer 13

HCO3-, glutamine, and ATP

Question 14

What are the precursors for pyrimidine synthesis converted into (1), and what is the enzyme that completes this first step (2)?

Answer 14

(1) carbamoyl phosphate
(2) carbamoyl phosphate synthetase II

Question 15

What is formed from carbamoyl phosphate (1), and what enzyme (2) and additive molecule (3) are involved?

Answer 15

(1) carbamoyl aspartate is formed by (2) aspartate transcarbamoylase which requires (3) aspartate

Question 16

What does carbamoyl aspartate form (1), via what enzyme (2) and what byproduct is made in the process (3)?

Answer 16

(1) Dihydroorotate–FIRST RING
(2) dihydroorotase
(3) H2O byproduct

Question 17

What kind of enzyme converts dihydroorotate to its product?

Answer 17

(1) a dehydrogenase removes H2

Question 18

What is formed from orotate (1), by what enzyme (2), and what is added at this point to help drive the reaction (3)?

Answer 18

(1) orotidylate
(2) orotate phosphoribosyl transferase
(3) PRPP moiety is added, with severing of pyrophosphate driving the reaction

Question 19

What is formed from orotidylate (1), by what enzyme (2), and what is produced (3)?

Answer 19

(1) uridylate (UMP)
(2) orotidylate decarboxylase
(3) CO2 produced

Question 20

How does UMP become UTP?

Answer 20

Kinases add two phosphate groups to UMP

Question 21

What is formed from UTP (1), by what enzyme (2), and what precursors are needed to complete this reaction (3)?

Answer 21

(1) CTP (cytidine triphosphate)
(2) cytidylate synthetase
(3) Glutamine, ATP, and H2O

Question 22

What are the differences in bacterial and animal regulation of pyrimidine biosynthesis?

Answer 22

In bacterial pyrimidine synthesis, ATP ACTIVATES aspartate transcarbamoylase (ATCase), and CTP INHIBITS ATCase (2nd enzyme in pathway) (AC: ATP activates, CTP inhibits)

In animal pyrimidine synthesis, ATP ACTIVATES carbamoyl phosphate synthetase II (1st enzyme in pathway) and UDP/UTP inhibit it. Also, UMP regulates orotate phosphoribosyl transferase (APUU: ATP and PRPP activate, UDP and UTP inhibit)

Question 23

What vitamin acts as a cofactor in the de novo synthesis of purines?

Answer 23

Folate, or vitamin B9