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Nucleotide Metabolism Flashcards

1
Q

What are nucleotides

A

phosphate esters of nucleosides

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2
Q

Nucleoside

A

Base + sugar

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3
Q

Nucleotide

A

nucleoside becomes a nucleotide when a phosphate group is added

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4
Q

Deoxynucleotides lack a _____

A

OH group, making it more stable

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5
Q

The sugar is connected to a base via a ________ bond

A

glycosidic

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6
Q

Purines

A 
2 rings
Adenine 
Guanine 
Xanthine 
Hypoxanthine
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7
Q

Pyrimidine

A

1 rings

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8
Q

Adenine is a _____

A

base

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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

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10
Q

Adding a phosphate group to adenosine?

A

adenosine-mono-phosphate (AMP)

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11
Q

Nucleosides and nucleotides have several roles

A

they can be

  1. cofactors
  2. regulatory roles by serving as signaling molecules
  3. stabilize
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12
Q

Where do carbons from purines and pyrimidines come from?

A

we can get them all over the place.

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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

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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
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15
Q

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

A

PPP

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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

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17
Q

R5P to PRPP is allosterically regulated

A

(+) Pi levels

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

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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.

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19
Q

What does PRA stand for

A

phosphoribosomal amine

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20
Q

Allosteric regulation when PRPP–> PRA

A

(+) PRPP

-) purine nucleotides like (GMP, AMP, IMP

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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.

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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).

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23
Q

In summary: what does methotrexate do?

A

It prevents the formation of purine-nucleotide ring formation

Doing this will inhibit DNA replication.

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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

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25
What type of inhibitor is methotrexate?
Methotrexate is a competitive inhibitor that binds to many things that use folate. It binds to DHF reductase more tightly!
26
What enzyme does methotrexate competitively inhibit?
Dihydrofolate reducatase.
27
Folic acid and ______ are very similar in structure
methotrexate
28
Step 4 of Purine Symthesis | Summary
We use the IMP to make AMP and GMP
29
_____ is the metabolic branch for the synthesis of AMP and GMP
IMP
30
How do we get from IMP to AMP?
2 reactions 1. [adenylosuccinate synthetase] converts IMP to adenylosuccinate monophosphate 2. Adenylosuccinase causes fumarate leaves and AMP is created!
31
How to we get from IMP to GMP?
1. IMP--> Xanthosine monophosphate (XMP) via IMP dehydrogenase 2. XMP--> GMP via GMP synthetase
32
Regulation in this pathway is cool. Why?
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!
33
AMP synthesis is stimulated by the presence of ______ in the purine synthesis path
GTP
34
GMP synthesis is stimulated by the presence of _____ in the purine synthesis pathway
ATP
35
What are SULFA drugs?
Sulfa drugs are competitive inhibitors that block the enzyme that put PABA into folate. Thus, they disrupt DNA replication in bacteria
36
Do SULFA drugs affect humans?
No, because we get folate from our diet.
37
Where does de novo synthesis of purines occur
cytosol
38
where does de novo synthesis of pyramidines occur
cytosol and mT
39
how is pyrimidine synthesis different from purine synthesis?
in pyrimidine synthesis: 1. make ring first 2. adda sugar
40
3 phases of pyrimidine synthesis
1. fabricate the orotate ring 2. Add PRPP to make UMP 3. Convert UMP--> CMP and TMP
41
1. Fabrication of the orotate ring
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
2. Add PRPP to become UMP
UMP synthetase will now add PRPP to orotate--> OMP--> UMP
43
3. UMP will now become CMP and TMP
UDP--> thymidlyate synthase --> dTMP UTP
44
How do we get from UDP--> dTMP
thymidylate reductase
45
asd
asd
46
2 regulatory points in pyrimidine synthase occur where
1. Carbamoyl phosphate synthetase II (commital step) | 2. ATCase (aspartate transcarbamoylase)
47
Regulation of carbamoyl phosphate synthetase
-UTP (this is a product, so why make more if we have some) +PRPP--> PRPP will promote the synthesis of purines and pyrimidines
48
Regulation of ATCase (aspartate transcarbamoylase)
in bacteria, it is inhibited by CTP
49
5 fluorouracil
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
Orotic aciduria
-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
how can we tx orotic aciduria
treat with uridine suppliment
52
5-fluorouracil is called
adrucil
53
Methotrexate prevents the _________ of ______
prevents the oxidation of DHF reductase
54
How do we treat orotic aciduria | ?
We treat it with oral uridine.
55
Orotic aciduria is a defect in _______
UMP synthase pathway
56
Orotic aciduria will leave to a buildup of _______ because it cannot be converted to ______
Orotic acid will lead to a build up of orotate because it cannot be converted to UMP.
57
5 fluoro uracil is called ______ and effects what enzyme
adrucil thymidlate synthase
58
Acyclovir is a
VIRUS! anti-viral medication that stops herpes and chicken pox from spreading
59
How does acyclovir work?
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
Nucleosidases
removes the ribose group and converts them itno pyrimidines and purines
61
the breakdown of purines all lead to what?
URIC ACID
62
GMP is broken down to
--> guanosine--> guanine--> xanthine- [xanthine oxidase]-> uric acid
63
AMP break down
AMP can be broken down into 1. IMP using AMP deaminase 2. adenosine--> inosine via adenosine deaminase
64
In purine catabolism, AMP and GMP will become
URIC ACID! All roads lead to uric acid
65
_____ inhibits xanthine oxidase
allopurinol
66
If you treated patients with allopurinol, what would happen to levels of xanthine and hypoxanthine
increase
67
What can we use to treat GOUT
allopurinol
68
What is GOUT?
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
which is more water soluble and why: xanthine or uric acid
xanthine because it has 2 oxygens. because it is more soluble, it can be excreted in our urine
70
when uric acid crystallizes, what does it form
MSU- monosodium urate
71
What joint is most affected in GOUT
metatarsal pharangeal joint
72
_____ is called the disease of the rich. Why
GOUT. can be caused by alot of wine and protein
73
How do we convert AMP--> IMP?
AMP deaminase
74
What enzyme is used to convert adenosine to inosine?
adenosine deaminase
75
Which enzyme must be balanced in our body? Meaning, too much and too little is bad. A. AMP deaminase B. Adenosine deaminase
A. Adenosine deaminase
76
Too much adenosine deaminase can do what
cause hemolytic anemia and fuck up RBC
77
Underproduction of adenosine deanimase can do what
Cause SCID (Severe combined immunodeficiency)
78
What causes SCID
an underproduction of Adenosine Deanimase, which converts adenosine--> inosine in purine breakdown
79
What are the end products of pyrimidine breakdown?
there are 2 catogories of products for pyrimidine breakdown; 1. ketogenic- malonyl coA 2. glucogen- methylmalonyl coA and succinly coA
80
Ketogenic breakdown products of pyrimidine breakdown
1. malonyl coA
81
Glucogenic breakdown products of pyrimidine breakdown
1. methylmalonyl coA and | 2. succinyl coA
82
What can we use to measure the breakdown of pyrimidine intermediate [dTDP and dTTP]?
we can measure levels of B-aminoisobutyrate in the urine
83
Renal lithiasis is a defiency of what
APRT
84
APRT is part what?
purine nucleotide salvage pathway
85
A defiency of APRT can cause
renal lithiases
86
Lesch Nyhan syndrome
caused by a defect in HGPRT enzyme, which leads to a buildup of GUANINE and hypoxanthine because they cannot be broken down
87
``` L E S C H ```
``` Lips and fingers are bittin off Excessive uric acid production Self-multation Ccumulation of guaninine and hypoxanthine HGPRT ```
88
Lesch syndrome can cause
GOUT
89
Acyclovir has selective affintity for
thymidine kinase
90
NADPH is used to
build things
91
NADH is used to
break things
92
HGPRT and APRT are salvage pathway enzymes for _______
PURINES

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