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B3 Biochem > Nucleotide Metabolism > Flashcards

Nucleotide Metabolism Flashcards

1
Q

Nucleotides are structural components of ___ and ___

A

DNA and RNA

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2
Q

Nucleotides are carriers of activated intermediates

A

UDP-glucose in glycogen formation

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3
Q

Nucleotides are structural components of several coenzymes…for ex:

A

CoA
NAD+
FAD
NADP+

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4
Q

Secondary messengers in signal transduction, such as

A

cAMP and cGMP

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5
Q

Energy currency of the cell, in the form as:

A

ATP

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6
Q

Nucleotides act as regulators of many pathways, like:

A

ATP or AMP activating or inhibiting a pathway

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7
Q

Summary of Nucleotide functions

A

Structural component (DNA RNA CoA FAD NADP+ and NADP+)
Carriers of activated intermediates (UDP-glucose)
Secondary messengers in signal transduction (cAMP and cGMP)
Energy currency of the cell (ATP)
Regulators of many pathways (ATP/AMP being an inhibitors/activator)

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8
Q

Features of the structure of Nucleotides

A

Nitrogenous base and sugar

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9
Q

Purines

A

Adenine

Guanine

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10
Q

Pyrimidine

A

Cytosine

Thymine(DNA)/Uracil(RNA)

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11
Q

Nucleotides as a sugar

A

Ribose in RNA and Deoxyribose as DNA

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12
Q

Nucleoside

A

Nitrogenous Base + Sugar

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13
Q

Nucleotide

A

Nucleoside + 1-3 phosphate groups

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14
Q

What part of nucleotides drive many biochemical reactions?

A

The anhydride bonds linking the 2nd and 3rd phosphate groups

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15
Q

Purine Nucleotide Synthesis

A
  • Ribose-5-P is from HMP Shunt
  • PRPP synthetase catalyzes the formation of the activated Pentose (Phosphoribosyl-pyrophosphate)
  • Nitrogenous base is attached at the 1’ carbon, where the pyrophosphate was attached
  • DNA/RNA is created
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16
Q

What does the default purine nucleotide synthesis do?

A

Produce ribonucleotides

If deoxyribonucleotides are needed, furthers steps are taken

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17
Q

Rate limiting step of Purine Synthesis

A

-Via PRPP Amidotransferase (regulated, committed step)

Inhibited by: purine nucleotides (end products)

Activated by: PRPP (substrate)

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18
Q

_________________ is required to make THF, which does what?

A

Dihydrofolate reductase

Creates Tetrahydrofolate, the form in which FOLATE is used as a CARBON DONOR

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19
Q

_______________ is a purine anaglog, which does what?

A

6-mercaptopurine.

Inhibits PRPP Amidotransferase (similar to high levels of natural purine inhibition)

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20
Q

What is Methotroxate?

A

A folic acid analog, an anti-tumor drug.

Inhibits DIHYDROFOLATE REDUCTASE

  • inhibiting nucleotide biosynthesis
  • inhibiting rapidly dividing cells selectively

(Works specifically in mammalian cells)

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21
Q

Sulfonamides and Purine Synthesis

A

Structural analogs of PABA (para-aminobenzoic acid)

Competitive inhibit of bacterial production of folic acid

Bacterial purine synthesis inhibited

Humans do not rely on folic acid synthesis and are unaffected

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22
Q

Sulfa drugs function as:

A

Antibiotics

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23
Q

What is the rate limiting step of Pyrimidine Nucleotide Synthesis?

A

CPSII, carbamoyl phosphate synthetase II

Activated by: PRPP

Inhibited by: UTP (end product)

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24
Q

CPS-1 is the rate limiting step of:

A

Urea cycle

25
Q

Pyrimidine synthesis key points

A

2 AAs become part of nitrogenous base structure of pyrimidines (GLUTAMINE and ASPARTATE)

PRPP provides the Pentose for the Pyrimidine

26
Q

Ribonucleotides can be converted into deoxyribonucleotides by:

A

Ribonucleotide reductase

27
Q

___________ is an anti-tumor drug that inhibits ribonucleotide reductase

A

Hydroxyurea

28
Q

Hydroxyurea functions

A

used to treat sickle cell anemia, but not related to its use as an anti-tumor drug

Increases the synthesis of fetal hemoglobin that can alleviate the effects of sickle cell hemoglobin

29
Q

dTMP is used in:

A

Deoxyribonucleotides

30
Q

_____________ is used in conversion from dUMP to dTMP, used in production of nucleic acids

A

Thymidylate synthase

31
Q

What inhibits thymidylate synthase? And therefore inhibits production of nucleic acids

A

5-FU, or 5-fluorouracil

32
Q

What 2 drugs affect the production of DNA, but not RNA?

A

Hydroxyurea and 5-FU

33
Q

A class of antibiotic that is selective for the prokaryotic version of dihydrofolate reductase

A

Trimethoprim

34
Q

Humans require ______ in the diet, while prokaryotes produce their own.

A

Folate

35
Q

An additional class of antibiotics that target enzymes in bacteria that make their own folic acid

A

Sulfonamides

Humans don’t have these enzymes
Selectively toxic to prokaryotes
Inhibit nucleotide metabolism

36
Q

Nucleotide metabolism

A

Pyrimidines are not salvaged to a significant degree

No high yield disease or enzymes are associated with their breakdown or salvage, so that pathway will not be discussed

37
Q

Why are purine bases more complex to synthesize than pyrimidines?

A

Purines are dicyclic, more steps involved, and salvage pathway is more critical.

38
Q

Salvage pathway of Purines

A

Nitrogenous base is recovered after removing phosphate and sugar moieties which yield HYPOXANTHINE or GUANINE, that can be shuttled back into purine nucleotide synthesis

39
Q

Adenosine deaminase deficiency

A

One of the causes of Severe Combined Immunodeficiency Disease (SCID)

T-cells and B-cells are particularly affected

Causes patients to be susceptible to almost any microorganism

Requires pt to be a bubble boy, lol

40
Q

Treatment for SCID

A

Bone marrow transplant, or enzyme replacement

Target for gene therapy trial

41
Q

During nucleotide metabolism, the base can be shuttled back into purine synthesis or:

A

Degraded to uric acid

Uses the intermediate xanthine, and xanthine oxidase

Excreted in urine

GOUT

42
Q

Gout is the result of:

A

Hyperuricemia

Accumulation of uric acid crystals in the joints

Leading to inflammation and gouty arthritis

43
Q

Gout is caused by:

A

Under excretion/overproduction of uric acid (most common)

Poor kidney function, acid-base imbalance, certain drugs

44
Q

In the overproducers of uric acid patients, or gout patients, what drug is used?

A

Allopurinol inhibits xanthine oxidase, which produces uric acid

45
Q

Lesch-Nyhan syndrome

A

Xlinked

Deficiency in the purine salvage pathway

Caused by defect in HGPRT

Deficit of purines

46
Q

HGPRT deficiency

A

Blockage of the pathway forces the purine degradation products into the production of uric acid

47
Q

Lesch-Nyhan Syndrome symptoms

A

Severe mental retardation

Self-destructive behavior, self-mutilation

48
Q

Gout can affect the eye by deposits of _____ in various locations

A

Tophi

49
Q

Tophi, side affect of gout, can be deposited in:

A 
Conjunctiva
Cornea
Iris
Sclera
Lens

Formation of transparent vesicles
Bleeding in subconjunctival space and vascular changes

50
Q

Functional roles of nucleotides and central role in storage of genetic information

A

DNA, RNA, ATP, AMP, cAMP, cGMP, CoA, FAD, NAD+, NADP+

51
Q

Distinguish between riconucleic acids and deoxyribonucleic acids

A

Ribose has an alcohol group on C2, deoxyribose has H on C2

52
Q

Ribose-5-P is obtained from:

A

HMP shunt

53
Q

List the positive and negative regulators

A

Activator: Pi

inhibitor: purine ribonucleotides

54
Q

Pyrophosphate and nitrogenous base are bound to:

A

1’ carbon of ribose

55
Q

Rate limiting/committed step of Purine Synthesis

A

PRPP Amidotransferase

Inhibited by: purine nucleotides

Activated by: PRPP

56
Q

Rate limiting step for Pyrimidine Synthesis

A

CPS II

Activated by: PRPP

Inhibited by: UTP

57
Q

Pyrimidine bases are produced then attached to:

A

PRPP

58
Q

Function of ribonucleotide reductase

A

Convert ribonucleotides into deoxyribonucleotides

59
Q

What inhibits ribonucleotide reductase

A

Hydroxyurea

Anti-tumor drug

Used to treat sickle cell anemia

Promotes HbF synthesis

B3 Biochem (4 decks)

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