Notes in Handout 5

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Status	Last Update	Fields
Published	11/25/2023	Name Purine Bases (3)
Published	11/26/2023	Name Pyrimidine Bases (3)
Published	11/26/2023	Nucleoside monophosphate (NMP) kinases:- Reaction at the {{c1::nucleotide}} level- Interconvert {{c1::NMP to NDP (reversible)}}- Base-specific- Does n…
Published	11/26/2023	Nucleoside diphosphate (NDP) kinase:- Reaction at the nucleotide level- Interconverts {{c1::nucleoside di- and tri- phosphates (reversible)}}- NOT bas…
Published	11/26/2023	Ribonucleotide reductase (RNR)- Converts {{c1::NDP}} to corresponding {{c1::dNDP}} irreversbily.- Under complicated allosteric control by {{c1::ATP}} …
Published	11/26/2023	RNR mechanism:-First step in catalysis requires a {{c1::tyr radical}} in active site.{{c2::Hydroxyurea}} is an RNR inhibitor drug:The mechanism of act…
Published	11/26/2023	RNR has 3 allosteric sites:1. {{c1::activity site (a-site)}}2. {{c1::Specificity site (s-site)}}3. {{c1::hexamerization site (h-site)}}RNR active site…
Published	11/26/2023	RNR How does it become active? inactive?Active: {{c1::ATP in a-site = h-site conformational change = allows ATP bind in h-site = R1 hexamer (active fo…
Published	11/26/2023	In RNR, ATP has a {{c1::higher}} Kd than dATP in the a-site.
Published	11/26/2023	Regulation of RNR:CDP ---> dCDP ---> dCTPThis reaction involves what enzymes and what in each site of the RNR?- {{c1::RNR and NDP kinase}}- a-si…
Published	11/26/2023	Regulation of RNR:UDP ---> dUDP ---> dTTPThis reaction involves what enzymes and what in each site of the RNR?- {{c1::RNR and NDP kinase}}- a-si…
Published	11/26/2023	Regulation of RNR:GDP ---> dGDP ---> dGTPThis reaction involves what enzymes and what in each site of the RNR?- {{c1::RNR and NDP kinase}}- a-si…
Published	11/26/2023	Regulation of RNR:ADP ---> dADP ---> dATPThis reaction involves what enzymes and what in each site of the RNR?- {{c1::RNR and NDP kinase}}- a-si…
Published	11/26/2023	De nono synthesis of purine:- Requires {{c1::backside attack of Nucleophile}}.- Requires {{c1::activation step}} for 1' carbon for a good leaving grou…
Published	11/26/2023	De novo synthesis pathway:{{c1::Glucose}} + hexokinase --> {{c1::G6P}} (undergoes pentose phosphate pathway) --> {{c1::R5P}} --> {{c1::PRPP}}…
Published	11/26/2023	R5P reacts with enzyme {{c1::ribose phosphate pyrophosphokinase}} with {{c1::ATP}} to form PRPP.This is the activation step to form purine nucleotides…
Published	11/26/2023	PRPP reacts with {{c1::enzyme amidophosphoribosyl transferase}} to form PRA.This involves {{c1::Glutamine and H2O.}}The enzyme has 2 active sites:1 fo…
Published	11/26/2023	IMP to AMP De Novo:1. IMP + {{c1::Aspartate}} + {{c1::GTP}} + (E: {{c2::adenylosuccinate synthetase}}) --> {{c1::Adenylosuccinate }}+ {{c1::GD…
Published	11/26/2023	IMP to GMP:1. IMP + NAD+ + H2O + (E: {{c2::IMP dehydrogenase}}) --> {{c1::XMP}} + NADH + H+2. {{c1::XMP}} + Glutamine + ATP + H2O +(E: {{…
Published	11/26/2023	Regulation of purine de novo synthesis:Inhibiting:- Pyrophosphokinase: {{c1::ADP and GDP}}- Aminophosphoribosyl: {{c2::AMP ADP ATP GMP GDP GTP XMP}}- …
Published	11/26/2023	Salvage of purine nucleotides:- Utilizes purine bases or nucleotides to form {{c1::nucleotides}}.- {{c2::Erythrocytes}} and {{c2::brain}} rely upon th…
Published	11/26/2023	Degradation of purine nucleotides:-AMP reacts with {{c1::AMP deaminase}} = IMP .. OR AMP reacts with {{c1::nucleotidase}} = Adenosine. Corre…
Published	11/26/2023	Uric acid has pka of {{c1::5.4}}.So dominant in aqueous form = very acidic. (ionized)Forms urate in blood.Release in urine.High concentrations with Na…
Published	11/26/2023	Mechanism of Allopurinol drug for gout:- {{c1::hypoxanthine}} analog.Binds to XO to undergo {{c2::C2 oxidation}} to become alloxanthine which has a ve…
Published	11/26/2023	De Novo of pyrimidine:Bicarbonate + 2 ATP + Glutamine + H2O (E: {{c1::CPSII}}) --> carbamoyl phosphate. Enzyme has 2 active sites.Product reacts wi…
Published	11/26/2023	UTP to CTP:Enzyme: {{c1::CTP synthetase}}.- uses Glutamine + ATP + H2O (has 2 active sites)
Published	11/26/2023	CTP = CDP --> dCDP = DCTP --> DNAEnzymes in each reaction: {{c1::NDP kinase, RNR, NDP kinase}}UDP --> dUDP = dUMP --> dTMP = dTDP = dTTP -…
Published	11/26/2023	Thymidylate synthase (TS):{{c1::Methylation}} of dUMP to form dTMP.Requires {{c1::N5,N10-methylene tetrahydrofolate (active)}} as cofactor.Cosume…
Published	11/26/2023	Thymidylate synthase (TS) 4 Steps of catalysis:1. {{c1::formation of TS-dUMP covalent complex}}2. {{c1::formation of TS-dUMP-folate covalent complex}}…
Published	11/26/2023	Regulation of pyrimidine de novo:Bacteria:ATCase activated by {{c1::ATP}} and inhibit by {{c1::CTP}}Humans:CPSII activated by {{c2::ATP}} and {{c2::PR…
Published	11/26/2023	Salvage of Pyrimidine:{{c1::Uridine Phosphorylase}}:- Uracil + R1P = Uridine + Pi (like PNP)- Cytosine = Cytidine (same as above){{c1::(d)Thymidine ph…
Published	11/26/2023	Degradation of pyrimidine:Mechanism same as purine. Once degraded to bases Uracil and Thymine, undergoes enzyme hydropyrimidine DH to reduce {{c1::C5 …
Published	11/26/2023	Folic Acid:- Required from the diet in humans. For {{c1::a.a. metabolism}} and {{c1::synthesis of nucleic acid}} precursors.- Structures into 3 parts:…
Published	11/26/2023	Dietary Folate:-Polyglutamate forms; may contain methyl group at N5.- Transported into bloodstream and methyl group must be removed for active folate …
Published	11/26/2023	FdUMP is a good drug to inhibit TS but is negativity charged so cannot pass membrane. 5FU is drug derived from FdUMP. Mechanism:1. 5FU can react …
Published	11/26/2023	Drugs to interfere with folate metabolismSulfonamides:-{{c1::PABA analog}}- Mammals cannot synthesize folate but bacteria do= perfect as antibiotics&n…
Status	Last Update	Fields