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76 Cards in this Set

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What is the precursor to Dopamine?
Tyrosine -(tyrosine hydroxylase) -> Dopa -(aromatic amino acid decarboxylase +PLP) -> Dopamine.
What is the precursor to Epinephrine?
Dopamine -(dopamine hydroxylase) -> Norepinephrine (phenlyethanolamine methlytransferase + adoMet) -> Epinephrine
What is the precursor to GABA?
Glutamate -(glutamate decarboxylase)->GABA
What is the precursor to histamine?
Histidine-(histidine decarboxylase+PLP)-> histamine
What is the precursor to Serotonin?
Trytophan -(tryptophan hydroxylase) ->5-hydroxytryptophan -(aromatic amino acid decarboxylase)-> serotonin
What is the precursor to Spermine?
Methionine and ornithine
What's the product of ornithine decarboxylation?
Putrescine
What enzyme is the target for treatment of African Sleeping Sickness? What's the inhibitor used?
Ornithine decarboxylation. DFMO is the suicide inhibitor that forms a covalent bond with the enzyme
What are examples of tetrapyrolles?
hemes, chlorophylls and coenzyme B12
What are examples of biological amines?
Neurotransmitters (Dopamine, Norephinephrine, Epinephrine, Serotonin, Histamine) and polyamines (spermine)
What are tetrapyrroles derived from?
Delta-aminolevulinate
What is the precursor molecule of tetrapyrroles?
Aminolevulinate which is dimerized and then tetramirized
What does degradation of heme yield
Biliverdin which is then reduced to bilirubin
Nucleotide vrs nucleoside
Nucleoside does not include the phosphates
Whats the difference between the pentose group of DNA and RNA?
In RNA there is a hydorxy group at the 2 C position, while DNA just has a hydrogen.
Where does base attach to pentose in the in pyrimdines?
N1
Where does base attach to pentose in the in purines?
N9
What are the functions of biological amines?
They functions as hormones and/or neurotransmitters.
Which biological amines are derived from tyrosine?
Dopamine
Norepinephrine
Epinephrine
Why biological amine comes from tryptophan?
Serotonin
Which biological amine comes from histidine?
Histamine
Many biological amines are generated decarboxylation of amino acids. How is this accomplished?
Aromatic amino acid decarboxylase and PLP
What are Delta-aminolevulinate derived from in animals?
Sunccinyl-CoA
Glycine
What are Delta-aminolevulinate derived from in plants?
Glutamate
What inhibits the formation of aminolevulinate?
Heme
How do you get tetrapyrroles from aminolevulinate?
Dimerized to form a heterocycle, which is then tetramized
Nucleoside adenine
Adenosine
Deoxyadenosine
Nuceloside of guanine
Guanosine
Deoxyguanosine
Nuceloside of cytosine
Cytidine
Deoxycytidine
Nuceloside of thymine
Thymidine or deoxythymidine
Nuceloside of uracil
Uridine
Nucleotide of adenine
Adenylate
Deoxyadenylate
Nucleotide of guanine
Guanylate
Deoxyguanylate
Nucleotide of cytosine
Cytidylate
Deoxycytidylate
Nucleotide of thymine
Thymidylate or deoxythymidylate (DNA)
Nucleotide of uracil
Uridylate (RNA)
Basic structure of nucleotides
Figure 8-1
In general, what is the difference between nucleotide biosynthesis of pyrimidines vs. purine?
In purines, bases are built stepwise onto RPPP.

In pyrimidines, a precursos base is synthesized and added to PRPP.
How is ribose 5-phosphate activated?
Addition of the pyrophosphate at the 1' position.

The hydrolysis of pyrophosphate drives the reaction forward.
In general, what is the similarity between nucleotide biosynthesis of pyrimidines vs. purine?
Free bases are NOT synthesized directly and added to PRPP.
In the purine ring, what nitrogen comes from the amide N of glutamine?
Figure 22-32
In the purine ring, what carbons comes from CO2?
Figure 22-32
In the purine ring, what carbons comes from formate?
Figure 22-32
In the purine ring, what carbons comes from glycine?
Figure 22-32
In the purine ring, what nitrogens comes from aspartate?
Figure 22-32
What is the primary regulation point purine biosynthesis? What factor acts as negative regulators?
The transfer of N amide of glutamine to the C1 of PRPP by glutamine-PRPP amidotransferase.

GMP, AMP, IMP
IMP
Inosinate, Branch point between GMP and AMP
From IMP, the synthesis of GMP uses which NTP as energy source?
ATP
From IMP, the synthesis of AMP uses which NTP as energy source?
GTP
In pyrimidine ring synthesis, which nitrogen and carbon atoms come from carbamoyl phosphate?
Figure 22-36
In pyrimidine ring synthesis, which nitrogen and carbon atoms come from aspartate?
Figure 22-36
What pool does carbamoyl phosphate come from?
A pool distinct from the urea cycle, found in the cytoplasm and synthesized by cytoplasmic CPS II
What is the pyrimidine ring precursor?
Orotate
From the synthesis of orotate to CTP, what other intermediates are required?
UMP and then, UTP
What is the commitment step in the synthesis of pyrimidines?
ATCase forms N-carbamoylaspartate from Asparate and Carbamoyl phosphate
What regulates ATCase?
CTP inhibits, while ATP relieves the inhibition.
What enzyme adds phosphates to nucleosides? What is the source of phosphates?
nucleoside mono/diphosphate kinase

the source is ATP
What enzyme removes the 2 'OH to form dNDP from rNDP?
Ribonucleotide reductase
Where are the initial electron carriers donating electrons to ribonucleotide reductase?
NADPH
After NADPH, what are the two electron donors to ribonucelotide reductase?
Thioredoxin

Glutaredoxin
What amino acid is reduce in passing electrons to ribonucleotide reductase?
Cysteine; disulfide bonds are broken down with the addition of electrons.
What molecule participates in the catalytic subunit of ribonucelotide reductase to transfer of electrons to the 2' OH?
Tyrosine free radical stabilized by iron atoms
In general, what are the different levels of regulation in ribonucelotide reductase?
Regulation at primary regulatory sites
Regulation at substrate specificity sites
What are the regulators at the primary regulatory site?
Positive regulation by ATP (energy charge)
Negative regulation by dATP (feedback)
What dTMP synthesized from? What is the enzyme? What molecule acts as a cofactor? What kind of reaction?
dUMP; thymidylate synthase, THF, one carbon reaction
Fluorouracil
Converted FdUMP, which Inhibits Thymidylate Synthase
Methotrexate
Inhibits dihydrofolate reductase, blocking regeneration of THF.
How do glutamine analogs acts as chemotherpeutics? What are example?
Glutamine analogs inhibit glutamine amidotransferase, which is a commitment step to purine synthesis.

Azaserine and acivicin
What is the general strategy for nucleotide degradation?
1) Removal of 5' phosphate to form the nucleoside
2) Removal of ribose to form the free base
What are purines degraded to finally?
Uric acid
What are pyrimidines degraded to finally?
Nitrogens are converted to Urea, while carbons are converted to succ-CoA
What causes gout?
Overproduction of uric acid from purine catabolsim
Salvage pathways
Allow production of AMP, IMP or GMP from free bases (adenine, guanine, hypoxanthine) combining with PRPP
What is the product of purine synthesis commitment step?
5-phosphoribosylamine
What is the enzyme used in the commitment step of purine synthesis?
glutamine-PRPP amidotransferase
What is the product of the pyrimidine commitment step?
N-carbamoylaspartate