Nucleotide and Heme Catabolism Flashcards

1
Q

What is the common catabolic product produced by adenosine and guanosine catabolism that is the substrate for generation of uric acid?

A

Xanthine

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2
Q

Final product of catabolism of cytidine and uridine is?

A

Acetyl-CoA

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3
Q

How are catecholamines inactivated? (Remember: what are catecholamines)

What enzyme catalyzes this?

A

Catecholamines are neurotransmitters–LDOPA derivatives

Oxidation–catalyzed by monoamine oxidase

Methylation–catalyzed by catechol-O-methyltransferase (COMT)

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4
Q

What enzymes degrade nucleic acids into oligonucleotides?

A

Nucleases

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5
Q

What enzymes degrade DNA?

A

DNases

Cleave the sugar-phosphate backbone

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6
Q

What enzymes degrade RNA?

A

RNases

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7
Q

What enzymes cleave oligonucleotides to generate mononucleotides?

A

Phosphodiesterases

Also cleaves the sugar phosphate backbone

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8
Q

What enzymes remove phosphate from nucleotides to make nucleosides?

A

Nucleotidases

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9
Q

What enzymes cleave nucleotides to generate bases and sugars?

A

Nucleosidases

cleaves glycosidic bond

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10
Q

How is AMP catabolized?

A

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

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11
Q

How is GMP catabolized?

A

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

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12
Q

AMP deamination to IMP pathway occurs in what tissues? How is AMP catabolized in other tissues?

A

Muscle

In other tissues, goes through adenosine

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13
Q

Why are there 2 AMP catabolism pathways?

A

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

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14
Q

What is uric acid?

A

End product of purine catabolism for humans and some other animals–primates and birds

Humans can’t break down the ring

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15
Q

What is gout?

A

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)

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16
Q

What are the causes of gout?

A

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

17
Q

How is gout treated?

A

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

18
Q

What is the effect of adenosine deaminase deficiency?

A

Excessive deoxyadenosine is toxic

Immune cells are particularly susceptible (why?) -> frequent infections

Similar case–purine nucleoside phosphorylase deficiency

19
Q

How are pyrimidines catabolized?

A

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
20
Q

How is heme metabolized?

A

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

21
Q

What is porphyria??

A

Defect in heme synthesis

Symptoms…extreme sensitivity to sunlight, anemia, etc.

22
Q

What is jaundice?

A

Excessive bilirubin in blood