Topic 16: Nucleotide Catabolism

Question 1

What are the Purines?

Answer 1

Adenine and Guanine

DOUBLE RING Structure

Question 2

What are the Pyrimidines?

Answer 2

Thymine, Cytosine and Uracil

SINGLE RING

Question 3

What is a nucleotide?

Answer 3

Base + Sugar + Phosphate

Question 4

What is a nucleoside?

Answer 4

Base + Sugar

Question 5

Simply stated, how are Pyrimidines broken down?

Answer 5

Eventually catabolized to CO2, H2O, and NH3.

Can potentially be used for energy.

(purines CANNOT be used for energy, waste only)

Question 6

What is significant about Thymine degradation?

Answer 6

It eventually becomes Propionyl CoA –> Succinyl CoA –> GLUCONEOGENIC

Beta-aminoisobutyrate (B-AIB) intermediate before Propionyl CoA

B-AIB can be measured in the blood to indicate CANCER, excessive cell death, follow Chemotherapy

Question 7

What is significant about Cytosine degradation?

Answer 7

1st step deaminated to make URACIL –> eventually becomes –> Acetate –> Acetyl CoA –> NOT GLUCONEOGENIC

Beta-Alanine intermediate before Acetate

Beta-Alanine and B-AIB from Thymine are structurally related to GABA and Glycine, inhibitory neurotransmitters.

Question 8

What is significant about Uracil degradation?

Answer 8

It comes from Cytosine degradation! Makes Acetyl CoA and is NOT GLUCONEOGENIC

Question 9

Simply stated, how are Purines broken down?

Answer 9

They become URIC ACID - cannot be utilized for energy, only waste!

Purine -> Uric Acid -> Renal Filtrate –> Reabsorption –> Liver –> Uric acid becomes ALLANTOIN –> excreted in urine

Question 10

What is the enzyme that breaks Uric Acid into Allantoin?

Answer 10

URICASE

Question 11

What animals excrete Uric Acid in their urine?

Answer 11

Primates, Birds (and Reptiles), Insects and DALMATIONS

Question 12

What animals further breakdown Allantoin for excretion?

Answer 12

Bony fish secrete Allantoic Acid through gills

Amphibians and Cartilaginous Fish secrete Glyoxylate and Urea in Urine

Question 13

What is Step 1 of GMP (purine) breakdown?

Answer 13

GMP Remove the Phosphate with Nucleotidase –> Guanosine

Question 14

What is Step 2 of GMP (purine) breakdown?

Answer 14

Guanosine Remove the Ribose via Purine Nucleotide Phosphorylase –> Guanine

Question 15

What is Step 3 of GMP (purine) breakdown?

Answer 15

Guanine Remove Amino group –> Xanthine

Question 16

How is AMP broken down?

Answer 16

AMP remove Phosphate –> Adenosine remove ribose –> Adenine remove amino group –> Hypoxanthine via Xanthine Oxidase –> Xanthine

AMP can be converted by Adenosine Deaminase to IMP pathway at any time by removing amino group. All roads lead to Xanthine.

Question 17

What happens to Xanthine once this step has been reached in purine breakdown?

Answer 17

Xanthine Oxidase converts it to URIC ACID

Question 18

What is Allopurinol?

Answer 18

A drug that inhibits XANTHINE OXIDASE, inhibiting Xanthine breakdown to URIC ACID.

Useful in treating Gout (humans and birds) and Kidney Stones in Dalmatians

Question 19

What happens in (1) Adenosine Deaminase deficiency?

Answer 19

Bubble Boy Syndrome!! (associated with SCID)

Adenosine accumulation –> Immundeficiency of both B and T cells

Prevents breakdown of Adenosine, buildup controls production of G nucleotide –> backup of purines inhibits both purine and pyrimidine synthesis –> everything’s fucked

Question 20

What happens in (2) Purine Nucleoside Phopshorylase deficiency?

Answer 20

SCID - Severe Combined Immunodeficiency

AMP and GMP buildup–> inhibits PRPP synthesis –> all nucleotide synthesis is inhibited –> leads to T-CELL DEFICIENCY

Cannot remove ribose

Question 21

Of the purine breakdown enzyme deficiencies, what happens in (3) Xanthine Oxidase deficiency?

Answer 21

Results in Gout or Urinary Stone formation.

Question 22

Of the purine breakdown enzyme deficiencies, what happens in (4) HGPRTase deficiency?

Answer 22

Lesch-Nyan Syndrome => self-mutilation!

X-linked recessive –> males only typically

Question 23

What is HGPRTase?

Answer 23

Hypoxanthine-Guanine Phosphoribosyltransferase – salvage pathway enzyme

Takes PRPP and puts sugar and phosphate back onto Purine to make IMP and Pyrophosphate (PPi)

Purine + PRPP via HGPRTase –> IMP + PPi

Question 24

What would a nucleotide rich diet consist of?

Answer 24

Testes and Thymus