Nucleotide and Heme Catabolism Flashcards
What is the common catabolic product produced by adenosine and guanosine catabolism that is the substrate for generation of uric acid?
Xanthine
Final product of catabolism of cytidine and uridine is?
Acetyl-CoA
How are catecholamines inactivated? (Remember: what are catecholamines)
What enzyme catalyzes this?
Catecholamines are neurotransmitters–LDOPA derivatives
Oxidation–catalyzed by monoamine oxidase
Methylation–catalyzed by catechol-O-methyltransferase (COMT)
What enzymes degrade nucleic acids into oligonucleotides?
Nucleases
What enzymes degrade DNA?
DNases
Cleave the sugar-phosphate backbone
What enzymes degrade RNA?
RNases
What enzymes cleave oligonucleotides to generate mononucleotides?
Phosphodiesterases
Also cleaves the sugar phosphate backbone
What enzymes remove phosphate from nucleotides to make nucleosides?
Nucleotidases
What enzymes cleave nucleotides to generate bases and sugars?
Nucleosidases
cleaves glycosidic bond
How is AMP catabolized?
AMP must be converted to xanthine–2 paths
1) deamination to generate IMP -> nucleotidase converts IMP to inosine
2) Nucleotidase cleaves to generate adenosine -> deaminated to inosine
Inosine cleaved by nucleosidase to produce hypoxanthine
Xanthine oxidase converts hypoxanthine to xanthine
How is GMP catabolized?
GMP must be converted to xanthine
1) nucleotidase generates guanosine
2) nucleosidase generates guanine
3) deamination of guanine produces xanthine
XMP must be converted to xanthine
1) nucleotidase generates xanthosine
2) nucleosidase generates xanthine
Xanthine oxidase converts xanthine to uric acid
AMP deamination to IMP pathway occurs in what tissues? How is AMP catabolized in other tissues?
Muscle
In other tissues, goes through adenosine
Why are there 2 AMP catabolism pathways?
The deamination pathway has a branching point in the muscle: IMP can react with aspartate to produce fumarate, which enters citric acid cycle–important to generate more energy
What is uric acid?
End product of purine catabolism for humans and some other animals–primates and birds
Humans can’t break down the ring
What is gout?
Disease caused by high uric acid levels
Uric acid can form crystals–causes inflammation, joint damage, arthritis, kidney malfunctions, tophi (uric acid deposits under the skin)
What are the causes of gout?
Elevated ribose-5-phosphate pyrophosphokinase activity–increase PRPP
Lesch Nyhan syndrome
Glucose-6-phosphatase deficiency–increase PRPP
Leukemia/chemotherapy–cell destruction increases uric acid
Lead poisoning–decreases uric acid excretion
How is gout treated?
Inhibit xanthine oxidase (why? Xanthine oxidase converts xanthine to uric acid)
Allopurinol does this–resembles tautomer of hypoxanthine, so xanthine oxidase uses it as a substrate -> produces very strong competitive inhibitor of the enzyme
What is the effect of adenosine deaminase deficiency?
Excessive deoxyadenosine is toxic
Immune cells are particularly susceptible (why?) -> frequent infections
Similar case–purine nucleoside phosphorylase deficiency
How are pyrimidines catabolized?
Humans can degrade pyrimidine rings
CMP, dCMP, UMP, dUMP are catabolized in one pathway
- CMP/dCMP are deaminated to UMP/dUMP
- Nucleotides are converted to deoxyuridine and uridine
- Uracil is cleaved from the nucleoside
- Uracil is degraded to acetyl CoA
dTMP is catabolized independently
- Nucleotidase and nucleosidase release thymine
- thymine is degraded to succinyl-CoA
How is heme metabolized?
When RBCs are destroyed, heme is catabolized in liver, spleen, bone marrow
Enzyme == heme oxygenase
Biliverdin = linearized green intermediate
bilirubin = yellow insoluble product, in blood binds albumin
- Antioxidant, but toxic
In liver, bilirubin is transformed into a bile pigment and secreted into gut
What is porphyria??
Defect in heme synthesis
Symptoms…extreme sensitivity to sunlight, anemia, etc.
What is jaundice?
Excessive bilirubin in blood
