Question Answer Purine degradation: significant activity occurs in the _____ digestive tract

**because all natural foods that we consume have nucleotides in them 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 Purine degradation:
inosine —> hypoxanthine Purine nucleoside phosphorylase (PNP) Purine degradation:
hypoxanthine (or PNP product) —> uric acid xanthine oxidase

**target enzyme for gout treatment to prevent production of uric acid Purine degradation:
AMP —> ? —> ? —> ?… AMP —> IMP —> Inosine
OR
AMP —> Adenosine —> Inosine
**can be deaminased and dephosphorylased in either order

Inosine —> Hypoxanthine —> uric acid 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) Oxidizes hypoxanthine to uric acid in liver, intestines (and milk) xanthine oxidase 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) 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 Gout can be exacerbated by ____ purine rich foods 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 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 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 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