Nucleotides & Folate

Question 1

Name 5 functions/derivatives of nucleotides

Answer 1

-Building blocks of DNA/RNA
-Biological energy transduction (ATP,GTP)
-Coenzymes (NAD, FAD, CoA)
-Signal transduction (cAMP)
-Carriers of activated intermediates (UDP-Glc)

Question 2

What are the 3 components of nucleotides?

Answer 2

-Nitrogenous base
-Pentose
-Phosphate

Question 3

What are the two types of nitrogenous bases? what are they?

Answer 3

Purines: adenine, guanine
Pyrimidines: Uracil, thymine, cytosine

Question 4

What is a nucleoside?

Answer 4

nitrogenous base linked to a sugar by an N-glycosidic bond

Question 5

What is the difference between an adenosine and a deoxyadenosine?

Answer 5

An adenosine is when the adenine of a nitrogenous base is linked to a ribose, the same is true for a deoxyadenosine except it is linked to a deoxyribose

Question 6

How are nucleotides and nucleosides related?

Answer 6

a nucleotide is a phosphorylated nucleoside

Question 7

What is CoA synthesized from?

Answer 7

cysteine, pantothenic acid, and ATP

Question 8

What is the function of FAD & NAD+?

Answer 8

they are coenzymes in redox rxns

Question 9

What is the function of S-Adenosyl Methionine (sAME)

Answer 9

it functions in methyl transfer rxns

Question 10

What is the function of cAMP and cGMP?

Answer 10

they are second messengers and intracellular signal transducers

Question 11

How are nucleotides linked in DNA/RNA?

Answer 11

they are linked 3’-5’ phosphodiester bonds catalyzed by polymersases

Question 12

What are the two ways to make purines?

Answer 12

-De Novo
-Recycling

Question 13

What are the 4 main components of purines?

Answer 13

-Aspartate
-Glycine
-2 forms of folate
-Glutamine

Question 14

Describe de novo purine synthesis

Answer 14

-ribose 5-phosphate - PRPP via PRPP synthase
- requires ATP
-10 steps (we dont need to know)
- Then the first ring is formed (using glycine, THF, glutamine, requires ATP)
-Formation of the second ring (using folate and aspartate) yields IMP
-IMP is converted to AMP and GMP

Question 15

Where are 3 steps you can regulate purine synthesis?

Answer 15

-PRPP synthase (inhibited by products)
-Adenylosuccinate synthase (negative feedback by AMP)
-IMP dehydrogenase (G branch: negative feedback by GMP)

Question 16

What are the 3 main components of pyrimidines?

Answer 16

Aspartate, glutamine, folate derivatives

Question 17

What is the main difference between purine and pyrimidine synthesis?

Answer 17

in pyrimidine synthesis the ring is formed BEFORE the sugar (PRPP) is added

Question 18

Describe the de novo synthesis of pyrimidines

Answer 18

-Glutamine + ATP +CO2 -> carbamoyl phosphate via carbamoyl phosphate synthetase 2
-CPS + glutamate + aspartate +… -> DHOA
- DHOA + PRPP (many steps later) -> UDP which can be converted to either TMP of UTP/CTP

Question 19

What is the difference between carbamoyl phosphate synthetase 1 & 2 ?

Answer 19

CPS 1: liver mitochondria, urea cycle, nitrogen source is NH4
CPS 2: cytosol of many cells, pyrimidine biosynthesis, nitrogen sources is glutamine

Question 20

What is the nitrogen source of CPS 2?

Answer 20

Glutamine

Question 21

How would you regulate pyrimidine synthesis?

Answer 21

stimulate/inhibit CPS2
inhibit: UTP (product)
stimulate: PRPP and ATP (reactants)

Question 22

What is the methyl donor to form dTMP from UDP?

Answer 22

folate derivative N5,N10-methylene tetrahyrolate

Question 23

What enzyme is used to convert dUMP to dTMP?

Answer 23

thymidylate synthase

Question 24

What critical biological process requires thymidylate synthase?

Answer 24

DNA replication

Question 25

Why is thymidylate synthase a target of chemotherapy drugs?

Answer 25

you can use inhibitors of thymidylate synthase to block DNA replication of rapidly growing cells

Question 26

True/False: breakdown of DNA and RNA is a continuous cell process

Answer 26

True

Question 27

What is dietary DNA/RNA digested in to?

Answer 27

oligonucleotides, nucleotides, free bases

Question 28

What are the turnover two fates of purine and pyrimidine nucleosides?

Answer 28

-degraded to waste products -salvages to reform nucleotides

Question 29

What are the fates of pyrimidine catabolism?

Answer 29

-Cytosine & Uracil: converted to beta-alanine -> acetyl CoA which can enter the TCA cycle -Thymine: converted to beta aminoisobutyric acid -> succinyl CoA which can enter the TCA cycle NH3 and CO2 are also formed which enter the urea cycle

Question 30

Describe the salvage of pyrimidine bases

Answer 30

-Uracil + ribose-1-P -> UMP via uridine phosphorylase -Thymine + deoxyribose-1-P to form TMP via thymidine phosphorylase

Question 31

Describe purine catabolism

Answer 31

adenosine and guanosine are both converted to xanthine which is converted to uric acid via xanthine oxidase

Question 32

how is uric acid excreted by different species?

Answer 32

great apes and Dalmatians excrete uric acid but other mammals concert uric acid to allantoin via uric oxidase

Question 33

What enzyme converts uric acid to allantoin?

Answer 33

urate oxidase

Question 34

What enzyme converts xanthine to uric acid?

Answer 34

xanthine oxidase

Question 35

From what does xanthine originate?

Answer 35

adenosone or guanosine

Question 36

Why don't great apes and humans just convert uric acid to allantoin which is more water soluble than uric acid?

Answer 36

they have accumulated mutations that result in a non functional urate oxidase

Question 37

True/False: uric acid is more water soluble than allantoin

Answer 37

false

Question 38

What happens when serum urate levels exceed the solubility limit?

Answer 38

crystals form in soft tissues and joints, kidney stones can form

Question 39

Why do dalmatians have higher levels of uric acid in blood and urine?

Answer 39

They are homozygous for the mutation in the SLC2A9 gene which leads to a defect in the ability to transport uric acid into hepatocytes for excretion

Question 40

What is a common medical problem of dalmatians caused by their method of uric acid excretion?

Answer 40

urinary tract stones

Question 41

How can you manage/prevent uroliths?

Answer 41

avoid high purine foods, increase hydration, rx diets, medications such as allopurinol

Question 42

How does allopurinol work? what is it a tx for?

Answer 42

it is a competitive inhibiter of xanthine oxidase which prevents the formation of uric acid. Helps prevent urinary stones in dalmatians

Question 43

What are two ways to salvage purine bases?

Answer 43

-purine phosphoribosylation by PRPP to form a purine 5 mononucleotide (aka AMP, IMP, GMP) -phosphoryl transfer from ATP to a purine ribonucleoside

Question 44

What vitamin is folic acid?

Answer 44

vit B 9

Question 45

Can animal synthesize folic acid?

Answer 45

no, it is synthesized by bacteria

Question 46

What must happen to folic acid before it can be absorbed?

Answer 46

dietary folic acid is typically polyglutamated, so glutamates are removed prior to absorption

Question 47

Where is folic acid absorbed?

Answer 47

proximal small intestine

Question 48

What occurs to "activate" folic acid into its derivatives?

Answer 48

- reduced to dihydrofolate and then to tetrahydrofolate via folic acid reductase

Question 49

What amino acid provides the methylene group to form N5, N10 methylene folate?

Answer 49

serine

Question 50

List 4 biological roles of folic acid

Answer 50

-One carbon metabolism -dTMP synthesis -Purine biosynthesis -DNA methylation

Question 51

What vitamin provides a methyl group for DNA methylation?

Answer 51

folate

Question 52

Why would megaloblastic anemia be a result of folate deficiency?

Answer 52

because it results in the inhibition of DNA synthesis during red blood cell production, so you have continued growth without division