Chm 635-16

Chm 635-16 - Purine Catabolism Most free purines and...

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1 Purine Catabolism • Most free purines and pyrimidines are salvaged, however some are catabolized • Birds, reptiles and primates (including humans) convert purines to uric acid Separation of base from (deoxy) ribose Purine-nucleoside phosphorylase (PNP) separates the free purine base from the ribose (or deoxyribose) (Deoxy)Nucleoside + P i Base + (Deoxy)- -D-Ribose 1-phosphate PNP
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2 The Major Pathways of Purine Catabolism Lead to Uric Acid The Major Pathways of Purine Catabolism Lead to Uric Acid Adenosine deaminase (ADA) converts AMP to IMP as part of the purine catabolism pathway. Lack of ADA is one cause of severe combined immunodeficiency syndrome (SCID).
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3 The Major Pathways of Purine Catabolism Lead to Uric Acid Purine degradation Xanthine oxidase: contains FAD, molybdenum, and non-heme iron. In primates, uric acid is the end product, which is excreted.
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4 The Purine Nucleotide Cycle in Skeletal Muscle Serves as an Anaplerotic Pathway Deamination of AMP to IMP by AMP deaminase , followed by resynthesis of AMP from IMP in de novo purine pathway enzymes, constitutes a purine nucleoside cycle (Figure 26.9) This cycle has the net effect of converting aspartate to fumarate plus NH 4 + This cycle is important – fumarate that is generated replenishes the levels of citric acid intermediates lost in amphibolic side reactions Skeletal muscle lacks the usual anaplerotic enzymes and relies on AMP deaminase for this purpose
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5 Major pathways of purine catabolism in animals. Clinical disorders of purine metabolism Excessive accumulation of uric acid: Gout The three defects shown each result in elevated de novo purine biosynthesis
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6 Gout results from excess sodium urate • Gout is caused from overproduction or inadequate excretion of uric acid • Sodium urate is relatively insoluble and can crystallize in tissues • Gout can be caused by a deficiency of hypoxanthine- guanine phosphoribosyltransferase (HGPRT) or defective regulation of purine biosynthesis
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7 Allopurinol is a treatment for gout • Allopurinol is converted in cells to oxypurinol, an inhibitor of xanthine dehydrogenase • Allopurinol prevents high levels of uric acid • Hypoxanthine, xanthine are more soluble Degradation of uric acid to ammonia. • Further catabolism of uric acid by other organisms
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8 Major pathways of pyrimidine catabolism in animals. Overview of Amino Acid Synthesis 1. Obtain N 2 in usable form. 2. Certain microorganisms reduce inert nitrogen to ammonia. It is the source of nitrogen for all amino acids. 3. Carbon skeleton comes from glycolytic pathway, PPP or citric acid cycle. 4. Sterochemical control. The strerochemistry at the a-carbon atom is established by transaminases that involves PLP. 5. Highly regulated, synthesized only when supplies are low.
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Chm 635-16 - Purine Catabolism Most free purines and...

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