Nucleotide Metabolism Flashcards

1
Q

What are nucleotides

A

phosphate esters of nucleosides

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Nucleoside

A

Base + sugar

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Nucleotide

A

nucleoside becomes a nucleotide when a phosphate group is added

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Deoxynucleotides lack a _____

A

OH group, making it more stable

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

The sugar is connected to a base via a ________ bond

A

glycosidic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Purines

A
2 rings
Adenine 
Guanine 
Xanthine 
Hypoxanthine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Pyrimidine

A

1 rings

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Adenine is a _____

A

base

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What happens when you add a sugar (deoxyribose) to adenine?

A

Adenosine

-ine means a sugar has been added and you have a NUCLEOSIDE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Adding a phosphate group to adenosine?

A

adenosine-mono-phosphate (AMP)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Nucleosides and nucleotides have several roles

A

they can be

  1. cofactors
  2. regulatory roles by serving as signaling molecules
  3. stabilize
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Where do carbons from purines and pyrimidines come from?

A

we can get them all over the place.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

In purine nucleotide synthesis, we begin with the synthesis of the ______ first, and then _______

A

PURINE (A, G, Xan, HypoXan) Synthesis, we begin with the synthesis of the SUGAR first

And then the RING formation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the 4 steps in purine ring formation

A
  1. Activate Ribose-5-phosphate
  2. Convert PRPP–> PRA
  3. Make an IMP Ring
  4. Create adenosine and guanosine nucleoTides
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

the ribose-5-phosphate that we begin with in purine ring formation comes from

A

PPP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Step 1 of Purine Ring formation

A
  1. We are going to convert R5P to its activated form PRPP via [PRPP synthetase]

R5P–> PRPP via [PRPP synthetase]

ATP is used

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

R5P to PRPP is allosterically regulated

A

(+) Pi levels

-) by purine nucleotides (why make more if you already have some

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Step 2 of Purine Ring Formation

A

PRPP–> PRA via [glutamine:PRPP amidotransferase)

This is the commital step! In this step, we substituted a pyrophosphate with an amino (NH3) group from glutamine.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What does PRA stand for

A

phosphoribosomal amine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Allosteric regulation when PRPP–> PRA

A

(+) PRPP

-) purine nucleotides like (GMP, AMP, IMP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Step 3

Create Inosine monophosphate (IMP) ring

A

PRA enters a 9 step reaction to create a ring.

We started with a sugar and build a ring on top.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is important to note about one of the 9 steps that occur in creating the ring.

A

When creating the ring, 2 of the carbons that are added will come from THF (tetrahydrofolate).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

In summary: what does methotrexate do?

A

It prevents the formation of purine-nucleotide ring formation

Doing this will inhibit DNA replication.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Methotrexate

A

Methotrexate interferes with the IMP ring formation in purine nucleotide formation.
It will attack dihydrofolate reductase, to prevent the conversion of folate to THF (which as we said, donates 2 carbons to the ring formation).

Thus, it will disrupt ring formation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What type of inhibitor is methotrexate?

A

Methotrexate is a competitive inhibitor that binds to many things that use folate.

It binds to DHF reductase more tightly!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What enzyme does methotrexate competitively inhibit?

A

Dihydrofolate reducatase.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Folic acid and ______ are very similar in structure

A

methotrexate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Step 4 of Purine Symthesis

Summary

A

We use the IMP to make AMP and GMP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

_____ is the metabolic branch for the synthesis of AMP and GMP

A

IMP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

How do we get from IMP to AMP?

A

2 reactions

  1. [adenylosuccinate synthetase] converts IMP to adenylosuccinate monophosphate
  2. Adenylosuccinase causes fumarate leaves and AMP is created!
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

How to we get from IMP to GMP?

A
  1. IMP–> Xanthosine monophosphate (XMP) via IMP dehydrogenase
  2. XMP–> GMP via GMP synthetase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Regulation in this pathway is cool. Why?

A

Because the products will exert regulation on themselves to promote the synthesis of the one another.

For example, if we have too much AMP, this will stop the production via [adenylosuccinate synthetase] and promote the synthesis of GMP!

And vice versa.

High GMP will tell IMP DH to sto!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

AMP synthesis is stimulated by the presence of ______

in the purine synthesis path

A

GTP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

GMP synthesis is stimulated by the presence of _____

in the purine synthesis pathway

A

ATP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

What are SULFA drugs?

A

Sulfa drugs are competitive inhibitors that block the enzyme that put PABA into folate.

Thus, they disrupt DNA replication in bacteria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Do SULFA drugs affect humans?

A

No, because we get folate from our diet.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Where does de novo synthesis of purines occur

A

cytosol

38
Q

where does de novo synthesis of pyramidines occur

A

cytosol and mT

39
Q

how is pyrimidine synthesis different from purine synthesis?

A

in pyrimidine synthesis:

  1. make ring first
  2. adda sugar
40
Q

3 phases of pyrimidine synthesis

A
  1. fabricate the orotate ring
  2. Add PRPP to make UMP
  3. Convert UMP–> CMP and TMP
41
Q
  1. Fabrication of the orotate ring
A
  1. HCO3- + NH3-Glu–> carbamoyl phoshphate via carbamoyl phosphote synthetase II
  2. Carbamoyl phosphate + Asp–> carbamoyl aspartate via aspartate transcarbamolyase
  3. Carbamoyl aspartate will then cause dihydrorotate to cyclize and enter the MT, where it will become ororotate

NOW: we have a fabricated ring!

42
Q
  1. Add PRPP to become UMP
A

UMP synthetase will now add PRPP to orotate–> OMP–> UMP

43
Q
  1. UMP will now become CMP and TMP
A

UDP–> thymidlyate synthase –> dTMP

UTP

44
Q

How do we get from UDP–> dTMP

A

thymidylate reductase

45
Q

asd

A

asd

46
Q

2 regulatory points in pyrimidine synthase occur where

A
  1. Carbamoyl phosphate synthetase II (commital step)

2. ATCase (aspartate transcarbamoylase)

47
Q

Regulation of carbamoyl phosphate synthetase

A

-UTP (this is a product, so why make more if we have some)

+PRPP–> PRPP will promote the synthesis of purines and pyrimidines

48
Q

Regulation of ATCase (aspartate transcarbamoylase)

A

in bacteria, it is inhibited by CTP

49
Q

5 fluorouracil

A

5 flurouracil is also called adrucil.

Is a cancer drug that blocks thymidylate synthase in the pyrimidinine synthesis pathway (particularly, it will prevent the formation of dTMP from UDP)

It is a cancer drug!

50
Q

Orotic aciduria

A

-hereditary defect in UMP synthase pathway.

Ororotate will appear in our urine. Because there is a defect in UMP synthase pathway, we cannot create UMP!

-as a result, lacking pyrimidines and get folate and vitB12 anemia.

51
Q

how can we tx orotic aciduria

A

treat with uridine suppliment

52
Q

5-fluorouracil is called

A

adrucil

53
Q

Methotrexate prevents the _________ of ______

A

prevents the oxidation of DHF reductase

54
Q

How do we treat orotic aciduria

?

A

We treat it with oral uridine.

55
Q

Orotic aciduria is a defect in _______

A

UMP synthase pathway

56
Q

Orotic aciduria will leave to a buildup of _______ because it cannot be converted to ______

A

Orotic acid will lead to a build up of orotate because it cannot be converted to UMP.

57
Q

5 fluoro uracil is called ______ and effects what enzyme

A

adrucil

thymidlate synthase

58
Q

Acyclovir is a

A

VIRUS!

anti-viral medication that stops herpes and chicken pox from spreading

59
Q

How does acyclovir work?

A

Acyclovir is anti-viral medication that selectively attacks thymidine kinases of viral infected cells. The thymidine kinases in these cells will convert acyclovir to a false nucleotide and it is inserted in DNA. It terminates DNA REPLICATION!

60
Q

Nucleosidases

A

removes the ribose group and converts them itno

pyrimidines and purines

61
Q

the breakdown of purines all lead to what?

A

URIC ACID

62
Q

GMP is broken down to

A

–> guanosine–> guanine–> xanthine- [xanthine oxidase]-> uric acid

63
Q

AMP break down

A

AMP can be broken down into

  1. IMP using AMP deaminase
  2. adenosine–> inosine via adenosine deaminase
64
Q

In purine catabolism, AMP and GMP will become

A

URIC ACID!

All roads lead to uric acid

65
Q

_____ inhibits xanthine oxidase

A

allopurinol

66
Q

If you treated patients with allopurinol, what would happen to levels of xanthine and hypoxanthine

A

increase

67
Q

What can we use to treat GOUT

A

allopurinol

68
Q

What is GOUT?

A

GOUT occurs when uric acid crystallizes in our peripheral extremeties.

Tx- we use allopurinal (something to inhibit xanthine oxidase) so that we will not have this buildup

69
Q

which is more water soluble and why: xanthine or uric acid

A

xanthine because it has 2 oxygens. because it is more soluble, it can be excreted in our urine

70
Q

when uric acid crystallizes, what does it form

A

MSU- monosodium urate

71
Q

What joint is most affected in GOUT

A

metatarsal pharangeal joint

72
Q

_____ is called the disease of the rich. Why

A

GOUT.

can be caused by alot of wine and protein

73
Q

How do we convert AMP–> IMP?

A

AMP deaminase

74
Q

What enzyme is used to convert adenosine to inosine?

A

adenosine deaminase

75
Q

Which enzyme must be balanced in our body? Meaning, too much and too little is bad.

A. AMP deaminase
B. Adenosine deaminase

A

A. Adenosine deaminase

76
Q

Too much adenosine deaminase can do what

A

cause hemolytic anemia and fuck up RBC

77
Q

Underproduction of adenosine deanimase can do what

A

Cause SCID (Severe combined immunodeficiency)

78
Q

What causes SCID

A

an underproduction of Adenosine Deanimase, which converts adenosine–> inosine in purine breakdown

79
Q

What are the end products of pyrimidine breakdown?

A

there are 2 catogories of products for pyrimidine breakdown;

  1. ketogenic- malonyl coA
  2. glucogen- methylmalonyl coA and succinly coA
80
Q

Ketogenic breakdown products of pyrimidine breakdown

A
  1. malonyl coA
81
Q

Glucogenic breakdown products of pyrimidine breakdown

A
  1. methylmalonyl coA and

2. succinyl coA

82
Q

What can we use to measure the breakdown of pyrimidine intermediate [dTDP and dTTP]?

A

we can measure levels of B-aminoisobutyrate in the urine

83
Q

Renal lithiasis is a defiency of what

A

APRT

84
Q

APRT is part what?

A

purine nucleotide salvage pathway

85
Q

A defiency of APRT can cause

A

renal lithiases

86
Q

Lesch Nyhan syndrome

A

caused by a defect in HGPRT enzyme, which leads to a buildup of GUANINE and hypoxanthine because they cannot be broken down

87
Q
L
E
S
C
H
A
Lips and fingers are bittin off
Excessive uric acid production
Self-multation
Ccumulation of guaninine and hypoxanthine
HGPRT
88
Q

Lesch syndrome can cause

A

GOUT

89
Q

Acyclovir has selective affintity for

A

thymidine kinase

90
Q

NADPH is used to

A

build things

91
Q

NADH is used to

A

break things

92
Q

HGPRT and APRT are salvage pathway enzymes for _______

A

PURINES