PURINES Flashcards
1. Purine: biochemistry, synthesis, and regulation 2. Uric acid: origin, elimination, and physicochemical properties 3. Crystals: factors affecting formation, induction of inflammation 4. Purine pathway enzyme deficiencies and immunodeficiency: ADA, PNP
What type of reabsorption correlates best with urate reabsorption.
Na+ reabsorption correlates best with urate reabsorption/retention, and Na+ retention with hyperuricemia.
What is the role of adenosine deaminase?
Adenosine is deaminated to inosine leaving an hydroxyl group. Enzyme is necessary for the purine salvage pathway. Absence results in purine deficiency with imune compromise and overexpression in hemolytic anemia. A similar gene is common to most life forms, bacteria to human.
What is the structure of purines and pyrimidines and how are they numbered?
Purines consist of 2 rings, a 6 membered ring with side C=C bound to N=C-N forming 5 membered ring with 9 positions. Nitrogens are at position 1, 3, 7. and 9 were 1 is a nitrogen beside the top C at position 6. Ribose attaches at position 9 (N). Position 6 Attaches to an amide in adenine and oxygen in guanine. Pyrimidines have 1 6 membered ring with nitrogens at position 1 and 3. Position 1 (N) attaches to ribose, 4 and 2 to amide and oxygen in cytosine, both to oxygen in uracil. Thiamine is uracil with a methyl group at position 5. Inositol has no double bonds and 6 hydroxyl groups. Base plus ribose is a nucleoside, if ribose phosphorylated a nucleotide.
What does 5’ nucleotidase (CD 73) do?
5’nucleotidase (CD 73, NT5E, ECTO-5-prime nucleotidase) converts nucleotides to nucleosides i.e. AMP to adenosine (not adenine). This occurs on the surface of various cell types. Mutations result in arterial and joint capsule calcification.
What does ectonucleotide pyrophosphatase do and where does it act?
ENPP1 (ectonucleotide pyrophosphatase) produces AMP and pyrophosphate from ATP, then CD73 produces adenosine and inorganic phosphate from AMP.
How is the basic purine ring formed?
5-Aminoimidazole-4-carboxamide ribonucleotide Transformylase/IMP Cyclohydrolayse (ATIC) generates IMP, from AICAR (C9H13N5O4, AICA Ribonucleotide, 5-amidoimidizole-4-carboxamide ribonucleotide). Purine synthesis is generated as needed directly from amino acids- glycine (N7, C5,C4), aspartate (N1), C from CO2(C6), 2 from N10-Formyl tetrahydrofolate (C2,C8) and 2 N from glutamine (N3,N9). N9 attaches to ribose C6 is at top of benzene ring, C4 and C5 are part of both rings, 5 is next to 6.
