Steps in the pathway for Inosine Monophosphate IMP
Bauchi Biochemistry
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Steps in the pathway for Inosine Monophosphate IMP
1 просмотр · 12 дн. назад
Bauchi Biochemistry
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1 просмотр · 12 дн. назад
Steps in the Pathway for Inosine Monophosphate (IMP) Synthesis
Inosine monophosphate (IMP) is the first fully formed purine nucleotide and the parent compound of AMP and GMP. It is made by the de novo purine synthesis pathway, which builds the purine ring directly on a ribose-5-phosphate backbone through 10 steps. It is a key topic in #Biochemistry and #MedicalLaboratoryScience. #IMP #PurineSynthesis
Where It Happens
Mainly in the liver cytosol, using ATP, amino acids, CO2 and folate carriers.
Steps of the Pathway
1. Ribose-5-phosphate is converted to PRPP (5-phosphoribosyl-1-pyrophosphate) by PRPP synthetase, using ATP.
2. PRPP + glutamine forms 5-phosphoribosylamine, catalyzed by glutamine-PRPP amidotransferase. This is the committed, rate-limiting step. #PRPP
3. Glycine is added to form glycinamide ribonucleotide (GAR), using ATP.
4. N10-formyl-THF donates a formyl group, forming formylglycinamide ribonucleotide (FGAR).
5. Glutamine donates a second nitrogen, forming formylglycinamidine ribonucleotide (FGAM), using ATP.
6. Ring closure forms the imidazole ring, giving 5-aminoimidazole ribonucleotide (AIR), using ATP.
7. CO2 is added to form carboxyaminoimidazole ribonucleotide (CAIR).
8. Aspartate is added to form SAICAR, using ATP.
9. Fumarate is released, giving AICAR (5-aminoimidazole-4-carboxamide ribonucleotide).
10. A second formyl group from N10-formyl-THF forms FAICAR, which cyclizes to form IMP. #FolateMetabolism
Sources of Purine Ring Atoms
Glycine (C4, C5, N7), glutamine (N3, N9), aspartate (N1), CO2 (C6) and formate from N10-formyl-THF (C2, C8). #NucleotideMetabolism
Regulation
IMP, AMP and GMP inhibit the amidotransferase step by feedback inhibition, while PRPP activates it. Excess PRPP raises purine production, contributing to #Gout.
From IMP to AMP and GMP
AMP: IMP + aspartate (using GTP) forms adenylosuccinate, then AMP
GMP: IMP is oxidized to XMP by IMP dehydrogenase, then aminated to GMP using ATP
Clinical Importance
Methotrexate lowers formyl-THF supply, mycophenolic acid blocks IMP dehydrogenase, and azathioprine interferes with purine synthesis. Defects cause disorders such as Lesch-Nyhan syndrome (salvage pathway) and gout. #Pharmacology
Understanding the IMP pathway explains nucleotide production, drug action and metabolic disease. #HealthAwareness #BiochemistryEducation #MedicalEducation #LabEducation