Nucleotide Synthesis and Degradation & DNA
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| Purine degradation: significant activity occurs in the _____ | digestive tract
**because all natural foods that we consume have nucleotides in them
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| Nucleotides are first converted to nucleoSIDES by intracellular ____ Nucleosides are then degraded by _____ These products are converted to XANTHINE by ____ and ____ | nucleotidases (under strict regulation to ensure substrates (often intermediates) are not depleted below critical levels
Purine nucleoside phosphorylase (PNP)
Guanine deaminase & xanthine oxidase
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| Purine degradation: inosine ---> hypoxanthine | Purine nucleoside phosphorylase (PNP)
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| Purine degradation: hypoxanthine (or PNP product) ---> uric acid | xanthine oxidase
**target enzyme for gout treatment to prevent production of uric acid
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| Purine degradation: AMP ---> ? ---> ? ---> ?... | AMP ---> IMP ---> Inosine
OR
AMP ---> Adenosine ---> Inosine
**can be deaminased and dephosphorylased in either order
Inosine ---> Hypoxanthine ---> uric acid
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| How many enzymes from IMP --> AMP? How many enzymes from AMP --> IMP? | IMP --> AMP = two enzymes (when making nucleotides
AMP --> IMP = one enzyme (when breaking down nucleotides)
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| Oxidizes hypoxanthine to uric acid in liver, intestines (and milk) | xanthine oxidase
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| Humans and other primates excrete ____ in the urine but most N goes out as ____ Birds, reptiles and insects excrete ____ as their major N excretory compound | Uric acid
Urea (MOST for humans and primates)
Uric acid (MOST for birds, reptiles)
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| Gout occurs from ____ Drug treatment? | accumulation of uric acid crystals in extremities (joint of big toe is particularly susceptible.
--urate crystals may appear in kidney stones and obstruct urinary tract
allopurinol, inhibits Xanthine Oxidase from making uric acid from hypoxanthine
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| Gout can be exacerbated by ____ | purine rich foods
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| Purine-Nucleotide cycle exhibits anaplerosis by _____ In what tissue is this process particularly important? | releases FUMARATE for TCA cycle
Contraction of SKELETAL MUSCLE: as AMP builds up, it is converted IMP then back to AMP with release of fumarate which provides more substrate for TCA cycle and stimulates oxidative metabolism for more energy
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| Lesch-Nyhan Syndrom results from a complete deficiency in ____ Presentation? | HGPRT (so can't salvage purines from production and excretion of uric acid); severe hyperuricemia
-severe, crippling arthritis due to accumulation of uric acid
-retardation
-self-mutilation/aggression
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| HGPRT (hypoxanthine-guanine phosphoribosyltransferase) = ? | HGPRT salvages purine at the stage of hypoxanthine (immediately before it would be converted to Uric acid and excreted)
adds ribose onto hypoxanthine (using alpha-PRPP) and converts to IMP or GMP
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| SCID is a group of related disorders involving _______ 30% of SCID patients lack the enzyme ______. In the absence of this enzyme, deoxyadenosine is not deaminated to ______ as normal | diminished immune response
adenosine deaminase
deoxyinosine
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