Purine metabolism Flashcards by Giovanna Zampierollo

ribose and base

nucleosides

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ribose and base and phosphate

nucleotides

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how can nucleotides be acquired?

salvage pathway or de Novo synthesis

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used for DNA, RNA or high energy intermediates

nucleotides

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aspartate, CO2, glycine, Glutamine x 2, N10-formyl-tetrahydrofolate

purines derivations

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purine synthesis begins with _______ and the formation of phosphoribosyl-1-pyrophosphate and 5- phosphoribosylamine

ribose-5-p

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ribose-5-p reacts with ATP and PRPP synthetase to form

PRPP

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used to create ribose-5-p

PPP

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PRPP reacts with _________ and amidophosphoribosyl transferase to form

glutamine to form 5-phosphoribosylamine

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which is the highly regulates step in which the glycosidic bond is formed

PRPP + Glutamine–> 5-phosphoribosylamine

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5-phosphoribosylamine reacts with _____ and ATP to form Ribose-P-Glycinamide ribonucleotide

glycine

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Ribose-P-Glycinamide ribonucleotide reacts with _________ to form Ribose-P-formylglycinAMIDE ribonucleotide

N10-Formyl-THF

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Ribose-P-Glycinamide ribonucleotide reacts with __________ and ATP to form Ribose-P-GlycinamIDINE ribonucleotide

Glutamine

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loss of ______ results in Ribose-P-5 aminoimidazole ribonucleotide

H2O

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carry out various methylation reactions and the one used in purine synthesis

folates and N10 formyl-THF

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5-Aminoimidazole-4-Carboxylate Ribonucleotide reacts with __________ and ATP to form 5-Aminoimidazole-4-N-Succinocarboxamide Ribonucleotide

Aspartate

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9.5-Aminoimidazole-4-N-Succinocarboxamide Ribonucleotide reacts and LOSES ________ to form 5-Aminoimidazole-4-Carboxamide Ribonucleotide

Fumarate

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Ribose-P-5-Aminoimidazole-Ribonucleotide loses _______ to form 5-Aminoimidazole-4-Carboxylate Ribonucleotide

CO2

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5-Aminoimidazole-4-Carboxamide Ribonucleotide reacts with ___________ to form 5-Formamidoimidazole-4-Carboxamide Ribonucleotide

N10-FORMYL-THF

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Loss of H2O from 5-Formamidoimidazole-4-Carboxamide Ribonucleotide results in formation of

INOSINATE

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IMP serves as a precursor for either

AMP or GMP

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synthesis of AMP requires

GTP

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Synthesis of GMP requires

ATP

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IMP reacts _____ and GTP to form intermediate then forms AMP

aspartate

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IMP reacts with _____ to form intermediate and then reacts with ____ and ATP to form GTP

IMP reacts with NAD+ and then with Glutamine

True or False: production of one purine nucleoside ihibits the production of the other

FALSE--> insures

conversion of Monophosphates to Diphosphates are done by _____ that are BASE-SPECIFIC; but not ______

KINASES that are not SUGAR-SPECIFIC

Nucleoside Diphosphate is converted to ______ by Nucleoside Diphosphate Kinase

TRIPHOSPHATE

Nucleoside Diphosphate Kinase

enzyme has broad-specificity

Enzymes needed for purine biosynthesis are in the

cytosol

de novo synthesis occurs actively in the

liver and placenta

Degraded cells in the body have their nucleotides reused

salvage pathway

Many chemotherapeutics or anti-viral agents are ____________ that are incorporated via salvage pathway

NUCLEOTIDE ANALOGUES

*BOTH De Novo Synthesis and Salvage Pathway begin with activated

PRPP

In the gut, the pancreas secretes

NUCLEASES and PHOSPHODIESTERASE

produce short oligonucleotides;

nucleases

produces mononucleotides

phosphodiesterase

In the gut, Nucleotidases cleave off Pi to form

Nucleoside

will cleave off sugar to give either PURINE/PYRIMIDINE

Nucleosidase

excess purines and pyrimidines are turned into

uric acid then urine

GUANINE + PRPP → GMP + PPi catalyzed by:

HGPRT

HYPOXANTHINE + PRPP → IMP +PPi catalyzed by:

HGPRT

ADENINE + PRPP → AMP + PPi catalyzed by:

APRT

AMP & GMP will inhibit the ___________ and STOP the conversion of IMP to their respective base

IMP branch point

Salvage Pathway begins with formation of AMP + GMP, thus SALVAGE PATHWAY SHUTS OFF

DE NOVO BIOSYNTHESIS

PRPP will ______ its own conversion to 5-Phosphoribosylamine via activation of Amidophoshporibosyl Transferase

activate

promotes synthesis of the other respective base

ATP/GTP

ADP/GDP will ______ conversion to ribose 5 P to PRPP

inhibit

AMP, ADP, ATP/GMP,GDP,GTP will FEEDBACK ________ PRPP conversion to 5-Phosphoribosylamine, via action on Amidophoshporibosyl Transferase

inhibit

expensive pathway

de novo biosynthesis

begins when PRPP levels accumulate and are excess

De Novo Biosynthesis

Nucleoside is converted into _______ via Adenosine Deaminase

INOSINE

INOSINE (nucleoside) is cleaved to form ______________ and Ribose-1-P under action of Purine Nucleoside Phosphorylase

Hypoxanthine

Nucleotides have a _________ thus they must be controlled and excreted carefully

nitrogen component

In general, nucleotides are excreted as

uric acid

Hypoxanthine is converted to Xanthine and then Uric Acid; both reactions are done by

Xanthine Oxidase

_____ is converted to Xanthine by Guanine Deaminase, then converted to Uric Acid by Xanthine Oxidase

Guanine

is characterized by ELEVATED URIC ACID levels in blood due to many metabolic abnormalities

Gout

In Gout, ______ are deposited in cartilage of joints and in the kidney, resulting in pain and disability

Urate Crystals

Gout is defective in [3]

HGRT and PRPP synthetase and Glucose 6 Phosphatase

Defective HGPRT means buildup of

Guanine + Hypoxanthine

PRPP will accumulate due to INACTIVATION of SALVAGE and thus causes

DE NOVO ACTIVATION

Lower levels of purines also cause less

feedback inhibitions

defective PRPP synthetase leads to

Enzyme no longer is susceptible to inhibition by purine nucleotides

Defective_______means increased use of PPP and excess production of Ribose-5-P, the PRPP precursor

defective glucose 6 phosphatase

Allopurinol is a competitive inhibitor of

Xanthine Oxidase

Drug keeps Uric Acid levels LOW; Xanthine and Hypoxanthine are excreted in urine

gout tx

Gout tends to accumulate in the extremities which are more

temperature sensitive

x-linked disorder lacking functional HGPRT

Lesh-Nyan syndrome

Self-mutilation, mental illness and gout like symptoms and leads to Increase in rate of purine biosynthesis by De Novo Pathway

Lesh-Nyan syndrome

HGPRT activity is highest in _________ suggesting importance of purine salvage pathway in this tissue

brain

what removes amine off nucleoside to form Inosine

Adenosine Deaminase

ADA causes _________- because of lack of B cells and Tcells

SEVERE COMBINED IMMUNODEFICIENCY

resemble para-Aminobenzoic and thus INHIBIT FOLATE SYNTHESIS and stop purine synthesis

Sulfonamides

Used in chemotherapy for treatment of Acute Leukemia

6-Mercaptopurine

6-Mercaptopurine Functions as a _______ prevents production of AMP and GMP

hypoxanthine analogue

Purine metabolism Flashcards

exam 4