M1 Biochemistry: 5. Nucleotide Biosynthesis

Front 1

Give examples of nucleotides that are components of
a) intracellular communication
b) intercellular communication

Back 1

a) intracellular: cellular messengers like cAMP, which is involved in activation o glycogenolysis
b) intercellular: ATP released by certain nerve terminalsthat act on postsynaptic receptors

Front 2

There are 2 types of pathways leading to nucleotide biosynthesis. What are they?

Back 2

1. De novo synthesis. Need Ribose 5-phosphate, certain amino acids, CO2, NH3

2. Salvage pathways. Nucleosides and free bases are "recycled".

Front 3

What are the four ingredients needed for De novo nucleotide biosynthesis?

Back 3

i. Ribose 5-phosphate
ii. certain amino acids
iii. CO2 (directly in the form of bicarbonate)
iv. NH3 (technically ammonium released from glutamine)

Front 4

In the De novo synthesis of purines, the first reaction yields....

Back 4

N #9 . It is the Amide N of glutamine.

Front 5

In De novo synthesis of purines, the second reaction yields...

Back 5

glycine (amino nitrogen plus 2 carbons)

Front 6

In De novo synthesis of purines, the third reaction yields...

Back 6

a carbon from Formate. 1 C transfer using N10-formyl-tetrahydrofolate.

Front 7

In De novo synthesis of purines, the fourth reaction yields...

Back 7

N #3 is another amide from glutamine

Front 8

In De novo synthesis of purines, the fifth reaction yields...

Back 8

a carbon from bicarbonate

Front 9

In De novo synthesis of purines, the sixth reaction yields...

Back 9

an amino nitrogen from aspartate

Front 10

In De novo synthesis of purines, the seventh reaction yields...

Back 10

a carbon from formate

Front 11

_______ is a substrate which plays a role in de novo biosynthesis in both purines and pyrimidines.

Back 11

PRPP

5-phosphoribosyl-1-pyrophosphate

Front 12

How do we make 5-phosphoribosyl-1-pyrophosphate (PRPP)? (What is the equation that yields it?)

Back 12

Ribose 5-Pi + ATP -> 5-PRPP + AMP Enzyme: Ribose phosphate pyrophosphokinase (highly allosterically regulated)

Front 13

PRPP is derived from Ribose 5-Pi + ATP. Where does the Ribose 5-Pi come from?

Back 13

Oxidation of Glucose-6-phosphate in the pentose phosphate pathway, which is highly active in cells that need to make antioxidants, cells that are involved in making a lot of fat and in cells that are involved in hyperplastic growth.

Front 14

PRPP is made from....

Back 14

Ribose 5-phosphate which is made from Glucose 6-phosphate.

Front 15

What is the committed step in purine de novo synthesis?

Back 15

The 1st step when the amide from glutamine becomes the N #9. Once we've made 5-Phospho-beta-D-ribosylamine.

Front 16

PRPP -- (first 1step committed rxn) --> 5-phospho-beta-D-ribosylamine ----(many rxns)---> _________ -----> adenylate (AMP) or guanylate (GMP)

Back 16

inosinate

note: that AMP synthesis requires GTP and GMP synthesis requires ATP

Front 17

In purine de novo synthesis, from the insoniate internediate, AMP sysnthesis requires ______ and GMP synthesis requires ______.

Back 17

AMP synthesis requires GTP ; GMP synthesis requires ATP.

Front 18

The conversion of GMP and AMP to triphosphates to be used in biosynthesis is carried out by...

Back 18

1) base-specific nucleoside monophosphate kinases (ex. AMP -> ADP)

2) Ubiquitous nucleside diphosphate kinase (ex. ADP -> ATP)

mono to di is A BASE SPECIFIC kinase while di to tri is a ubiquitous one!!

Front 19

What is purine's nucleotide synthesis control mechanisms?

Back 19

There are three mentioned. First level: feedback inhibition of the first committed step (PRPP to 5-phosphoribosyylamine) by AMP, GMP, IMP. Second level: short feedback loops of AMP regulating AMP, GMP regulating GMP. Third level: "balancing" b/c to make AMP need GTP and to make GMP need ATP.

Front 20

The de novo biosynthesis of pyrimidines differs from that of the purines in that...

Back 20

the base is created initially and then it is attached to PRPP later whereas in purine de novo biosynthesis starts upon the substrate PRPP. With pyrimidines, the formation of carbamoyl phosphate is first.

Front 21

The formation of _________ is the FIRST STEP in de novo pyrimidine biosynthesis. What is the reaction that yields this first step?

Back 21

Formation of carbamoyl phosphate.

Glu + CO2 + ATP -----> carbamoyl phosphate