Neucloetides Metaboilism- week 4 Flashcards
Nucloetide vs side
Nucleic acid?
Side- sugar and base
Tide- sugar base and phosphate
Nucleic acid- chain of nucloetides
Purines vs Pyridines
Purines- A and G
Pyridines- C, U , T
What bases and sugar does DNA use? RNA?
DNA- deoxyribose- A, T, C, G
RNA- ribose A, U, C and G
Functions of Nucleotides
- Building block for DNA and RNA
- Energy supply from high energy P-P (ATP and GTP)- quick through hydrolyzation
- Coenzymes that have nucleotide portion- NAD, NADP, FAD, CoA
- Ingredients for active metabolic precursors
- Physiological Mediators- Signal transduction (GTP), cAMP, Adenosine (regulates blood flow),
- Allosteric effectos of metabolic enzymes
Source of nucleotide
- Diet (5%)- plants/animals- anything with cells
- De novo synthesis
- Salvage from existing bases (majority)- because synthesis purines and pyridines is expensive
Exmaple the digestion of DNA/Nucleic Acids
Nucleotides- denatured in the stomach but mostly digested by pancreatic enzymes
Nucleases make oligonucleotides
Phosphodiesterases- mononucleotides
Nucleotidases make nucleosides
Nucelsidases make- base
Absorption of Nucleic Acids
Sugars (most absorbed and reused to PPP or channeled to glycolysis) taken up by intestinal mucosal cells and enter circulation
Bases- only 5% enter circulation because mucosal cells degrade them so they are converted to uric acid and excreted. This is why we need salvage and de novo synthesis because we excrete what comes in from diet
Disorders in Nucleotides Metabolism
Gout- purine synthesis or degradation
Lesch-nyhan- defecnt in purine salvage
Orotic aciduria- defect in de novo pyriminidine synthesis
CMB agents- drugs that block de novo pathways are successfully used as chemo agents
Rate limiting step of purine de novo snthesis
PRPP—glutamine phosphoribosyl amidotransferase–> IMP
Down regulated by IMP, AMP, GMP (downstream products)
upregulated by PEPP
Methotroxeate
Acts on steps where formyl THF is needed- this is a component of purine synthesis so this drug stops purine synthesis
What does myochenolic acid do
It inhibts IMP DH so does not allo T and B cells to form
What enzyme is regulated in purine degradation? What drug treats it?
Xanthine Oxidase- this enzyme can take electrons nad protons to the electron transport chain and is the one means of energy from purine degradation
Can be inhibited by allopurinol and this drug is given to ppl who have accumulation of uric acid because hypoxanthine and xanthine are easier to excrete
Consequences of gout
Treatments
Acute inflmmation and kidney stones
Colchicine- acts on leukocytes and tappers down inflmmatio doesn’t solve the main problem
Urisouric acid- help promote excretion of uric acid
Alloputurinol- inhibit xanthineoxidase which decrease the amount of uric acid produce and allow purines to be secreted as hypoxanthine and xanthine
What two enzymes are important in the salvage pathway
HGRTase and APRTase
Hypoxanthine– HGRTase—> IMP
Gaunine— HRGTase–> GMP
Adenine— APRTase–> AMP