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Biochem + Metabolism > Nucleotides & Folate > Flashcards

Nucleotides & Folate Flashcards

1
Q

Name 5 functions/derivatives of nucleotides

A

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

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2
Q

What are the 3 components of nucleotides?

A

-Nitrogenous base
-Pentose
-Phosphate

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3
Q

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

A

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

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4
Q

What is a nucleoside?

A

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

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5
Q

What is the difference between an adenosine and a deoxyadenosine?

A

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

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6
Q

How are nucleotides and nucleosides related?

A

a nucleotide is a phosphorylated nucleoside

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7
Q

What is CoA synthesized from?

A

cysteine, pantothenic acid, and ATP

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8
Q

What is the function of FAD & NAD+?

A

they are coenzymes in redox rxns

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9
Q

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

A

it functions in methyl transfer rxns

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10
Q

What is the function of cAMP and cGMP?

A

they are second messengers and intracellular signal transducers

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11
Q

How are nucleotides linked in DNA/RNA?

A

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

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12
Q

What are the two ways to make purines?

A

-De Novo
-Recycling

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13
Q

What are the 4 main components of purines?

A

-Aspartate
-Glycine
-2 forms of folate
-Glutamine

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14
Q

Describe de novo purine synthesis

A

-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

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15
Q

Where are 3 steps you can regulate purine synthesis?

A

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

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16
Q

What are the 3 main components of pyrimidines?

A

Aspartate, glutamine, folate derivatives

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17
Q

What is the main difference between purine and pyrimidine synthesis?

A

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

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18
Q

Describe the de novo synthesis of pyrimidines

A

-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

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19
Q

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

A

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

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20
Q

What is the nitrogen source of CPS 2?

A

Glutamine

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21
Q

How would you regulate pyrimidine synthesis?

A

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

22
Q

What is the methyl donor to form dTMP from UDP?

A

folate derivative N5,N10-methylene tetrahyrolate

23
Q

What enzyme is used to convert dUMP to dTMP?

A

thymidylate synthase

24
Q

What critical biological process requires thymidylate synthase?

A

DNA replication

25
Q

Why is thymidylate synthase a target of chemotherapy drugs?

A

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

26
Q

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

A

True

27
Q

What is dietary DNA/RNA digested in to?

A

oligonucleotides, nucleotides, free bases

28
Q

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

A

-degraded to waste products
-salvages to reform nucleotides

29
Q

What are the fates of pyrimidine catabolism?

A

-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

30
Q

Describe the salvage of pyrimidine bases

A

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

31
Q

Describe purine catabolism

A

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

32
Q

how is uric acid excreted by different species?

A

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

33
Q

What enzyme converts uric acid to allantoin?

A

urate oxidase

34
Q

What enzyme converts xanthine to uric acid?

A

xanthine oxidase

35
Q

From what does xanthine originate?

A

adenosone or guanosine

36
Q

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

A

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

37
Q

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

A

false

38
Q

What happens when serum urate levels exceed the solubility limit?

A

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

39
Q

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

A

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

40
Q

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

A

urinary tract stones

41
Q

How can you manage/prevent uroliths?

A

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

42
Q

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

A

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

43
Q

What are two ways to salvage purine bases?

A

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

44
Q

What vitamin is folic acid?

A

vit B 9

45
Q

Can animal synthesize folic acid?

A

no, it is synthesized by bacteria

46
Q

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

A

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

47
Q

Where is folic acid absorbed?

A

proximal small intestine

48
Q

What occurs to “activate” folic acid into its derivatives?

A
  • reduced to dihydrofolate and then to tetrahydrofolate via folic acid reductase
49
Q

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

A

serine

50
Q

List 4 biological roles of folic acid

A

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

51
Q

What vitamin provides a methyl group for DNA methylation?

A

folate

52
Q

Why would megaloblastic anemia be a result of folate deficiency?

A

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

Biochem + Metabolism (15 decks)

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