List the steps leading to the formation of Uridine monophosphate (UMP) and identify the final product of purine nucleotide catabolism in mammals.
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List the steps leading to the formation of Uridine monophosphate (UMP) and identify the final product of purine nucleotide catabolism in mammals.
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You're on a roll — let's continue with the biosynthesis of Uridine monophosphate (UMP).
1. (iii) List the (in their order) leading to the formation of Uridine monophosphate.
The de novo synthesis of Uridine Monophosphate (UMP) involves the following steps:
Carbamoyl phosphate synthesis: Bicarbonate (HCO3−) and ammonia (NH3) combine with 2 ATP to form carbamoyl phosphate, catalyzed by carbamoyl phosphate synthetase II.
Formation of carbamoyl aspartate: Carbamoyl phosphate reacts with aspartate to form carbamoyl aspartate, catalyzed by aspartate transcarbamoylase (ATCase).
Ring closure: Carbamoyl aspartate undergoes intramolecular cyclization to form dihydroorotate, catalyzed by dihydroorotase.
Dehydrogenation: Dihydroorotate is oxidized to orotate, catalyzed by dihydroorotate dehydrogenase, producing FADH2.
Addition of PRPP: Orotate reacts with 5-phosphoribosyl-1-pyrophosphate (PRPP) to form orotidylate (OMP), catalyzed by orotate phosphoribosyltransferase (OPRT).
Decarboxylation: Orotidylate (OMP) is decarboxylated to form Uridine Monophosphate (UMP), catalyzed by orotidylate decarboxylase.
Now, let's move to question 2.
2. (i) What is the name of the final product of purine nucleotide catabolism in mammals?
The final product of purine nucleotide catabolism in mammals is uric acid.
(ii) Illustrate the pathways of degradation purine nucleotides, for each step; include all the intermediates and enzyme involved.
Purine nucleotide degradation pathways for AMP and GMP converge to form uric acid.
Degradation of AMP:
Deamination: Adenosine monophosphate (AMP) is deaminated to Inosine monophosphate (IMP) by AMP deaminase.
AMPAMPdeaminaseIMP+NH3
Dephosphorylation: IMP is dephosphorylated to Inosine by 5'-nucleotidase.
IMP5′−nucleotidaseInosine+Pi
Glycosidic bond cleavage: Inosine is cleaved to Hypoxanthine and Ribose-1-phosphate by purine nucleoside phosphorylase (PNP).
InosinePurinenucleosidephosphorylaseHypoxanthine+Ribose-1-phosphate
Oxidation: Hypoxanthine is oxidized to Xanthine by xanthine oxidase.
Hypoxanthine+O2+H2OXanthineoxidaseXanthine+H2O2
Degradation of GMP:
Dephosphorylation: Guanosine monophosphate (GMP) is dephosphorylated to Guanosine by 5'-nucleotidase.
GMP5′−nucleotidaseGuanosine+Pi
Glycosidic bond cleavage: Guanosine is cleaved to Guanine and Ribose-1-phosphate by purine nucleoside phosphorylase (PNP).
GuanosinePurinenucleosidephosphorylaseGuanine+Ribose-1-phosphate
Deamination: Guanine is deaminated to Xanthine by guanine deaminase.
Guanine+H2OGuaninedeaminaseXanthine+NH3
Common Pathway to Uric Acid:
Oxidation: Xanthine (from both AMP and GMP pathways) is oxidized to Uric acid by xanthine oxidase.
Xanthine+O2+H2OXanthineoxidaseUricacid+H2O2
(iii) Name the two enzymes that can be used to recover purine bases in form of nucleotides and illustrate the reactions they catalyze.
The two main enzymes involved in the purine salvage pathway are:
Adenine phosphoribosyltransferase (APRT)
This enzyme salvages adenine by converting it directly into Adenosine Monophosphate (AMP).
Adenine+PRPPAPRTAMP+PPi
Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)
This enzyme salvages both hypoxanthine and guanine, converting them into their respective mononucleotides, Inosine Monophosphate (IMP) and Guanosine Monophosphate (GMP).
Hypoxanthine+PRPPHGPRTIMP+PPiGuanine+PRPPHGPRTGMP+PPi
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You're on a roll — let's continue with the biosynthesis of Uridine monophosphate (UMP). 1. (iii) List the (in their order) leading to the formation of Uridine monophosphate. The de novo synthesis of Uridine Monophosphate (UMP) involves the following steps: 1. Carbamoyl phosphate synthesis: Bicarbonate (HCO_3^-) and ammonia (NH_3) combine with 2 ATP to form carbamoyl phosphate, catalyzed by carbamoyl phosphate synthetase II. 2. Formation of carbamoyl aspartate: Carbamoyl phosphate reacts with aspartate to form carbamoyl aspartate, catalyzed by aspartate transcarbamoylase (ATCase). 3. Ring closure: Carbamoyl aspartate undergoes intramolecular cyclization to form dihydroorotate, catalyzed by dihydroorotase. 4. Dehydrogenation: Dihydroorotate is oxidized to orotate, catalyzed by dihydroorotate dehydrogenase, producing FADH_2. 5. Addition of PRPP: Orotate reacts with 5-phosphoribosyl-1-pyrophosphate (PRPP) to form orotidylate (OMP), catalyzed by orotate phosphoribosyltransferase (OPRT). 6. Decarboxylation: Orotidylate (OMP) is decarboxylated to form Uridine Monophosphate (UMP), catalyzed by orotidylate decarboxylase. Now, let's move to question 2. 2. (i) What is the name of the final product of purine nucleotide catabolism in mammals? The final product of purine nucleotide catabolism in mammals is uric acid. (ii) Illustrate the pathways of degradation purine nucleotides, for each step; include all the intermediates and enzyme involved. Purine nucleotide degradation pathways for AMP and GMP converge to form uric acid. Degradation of AMP: 1. Deamination: Adenosine monophosphate (AMP) is deaminated to Inosine monophosphate (IMP) by AMP deaminase. AMP AMP deaminase IMP + NH_3 2. Dephosphorylation: IMP is dephosphorylated to Inosine by 5'-nucleotidase. IMP 5'-nucleotidase Inosine + P_i 3. Glycosidic bond cleavage: Inosine is cleaved to Hypoxanthine and Ribose-1-phosphate by purine nucleoside phosphorylase (PNP). Inosine Purine nucleoside phosphorylase Hypoxanthine + Ribose-1-phosphate 4. Oxidation: Hypoxanthine is oxidized to Xanthine by xanthine oxidase. Hypoxanthine + O_2 + H_2O Xanthine oxidase Xanthine + H_2O_2 Degradation of GMP: 1. Dephosphorylation: Guanosine monophosphate (GMP) is dephosphorylated to Guanosine by 5'-nucleotidase. GMP 5'-nucleotidase Guanosine + P_i 2. Glycosidic bond cleavage: Guanosine is cleaved to Guanine and Ribose-1-phosphate by purine nucleoside phosphorylase (PNP). Guanosine Purine nucleoside phosphorylase Guanine + Ribose-1-phosphate 3. Deamination: Guanine is deaminated to Xanthine by guanine deaminase. Guanine + H_2O Guanine deaminase Xanthine + NH_3 Common Pathway to Uric Acid: 1. Oxidation: Xanthine (from both AMP and GMP pathways) is oxidized to Uric acid by xanthine oxidase. Xanthine + O_2 + H_2O Xanthine oxidase Uric acid + H_2O_2 (iii) Name the two enzymes that can be used to recover purine bases in form of nucleotides and illustrate the reactions they catalyze. The two main enzymes involved in the purine salvage pathway are: 1. Adenine phosphoribosyltransferase (APRT) This enzyme salvages adenine by converting it directly into Adenosine Monophosphate (AMP). Adenine + PRPP APRT AMP + PP_i 2. Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) This enzyme salvages both hypoxanthine and guanine, converting them into their respective mononucleotides, Inosine Monophosphate (IMP) and Guanosine Monophosphate (GMP). Hypoxanthine + PRPP HGPRT IMP + PP_i Guanine + PRPP HGPRT GMP + PP_i What's next?