Topic 16: Nucleotide Catabolism Flashcards
What are the Purines?
Adenine and Guanine
DOUBLE RING Structure
What are the Pyrimidines?
Thymine, Cytosine and Uracil
SINGLE RING
What is a nucleotide?
Base + Sugar + Phosphate
What is a nucleoside?
Base + Sugar
Simply stated, how are Pyrimidines broken down?
Eventually catabolized to CO2, H2O, and NH3.
Can potentially be used for energy.
(purines CANNOT be used for energy, waste only)
What is significant about Thymine degradation?
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
What is significant about Cytosine degradation?
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.
What is significant about Uracil degradation?
It comes from Cytosine degradation! Makes Acetyl CoA and is NOT GLUCONEOGENIC
Simply stated, how are Purines broken down?
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
What is the enzyme that breaks Uric Acid into Allantoin?
URICASE
What animals excrete Uric Acid in their urine?
Primates, Birds (and Reptiles), Insects and DALMATIONS
What animals further breakdown Allantoin for excretion?
Bony fish secrete Allantoic Acid through gills
Amphibians and Cartilaginous Fish secrete Glyoxylate and Urea in Urine
What is Step 1 of GMP (purine) breakdown?
GMP Remove the Phosphate with Nucleotidase –> Guanosine
What is Step 2 of GMP (purine) breakdown?
Guanosine Remove the Ribose via Purine Nucleotide Phosphorylase –> Guanine
What is Step 3 of GMP (purine) breakdown?
Guanine Remove Amino group –> Xanthine
How is AMP broken down?
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.
What happens to Xanthine once this step has been reached in purine breakdown?
Xanthine Oxidase converts it to URIC ACID
What is Allopurinol?
A drug that inhibits XANTHINE OXIDASE, inhibiting Xanthine breakdown to URIC ACID.
Useful in treating Gout (humans and birds) and Kidney Stones in Dalmatians
What happens in (1) Adenosine Deaminase deficiency?
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
What happens in (2) Purine Nucleoside Phopshorylase deficiency?
SCID - Severe Combined Immunodeficiency
AMP and GMP buildup–> inhibits PRPP synthesis –> all nucleotide synthesis is inhibited –> leads to T-CELL DEFICIENCY
Cannot remove ribose
Of the purine breakdown enzyme deficiencies, what happens in (3) Xanthine Oxidase deficiency?
Results in Gout or Urinary Stone formation.
Of the purine breakdown enzyme deficiencies, what happens in (4) HGPRTase deficiency?
Lesch-Nyan Syndrome => self-mutilation!
X-linked recessive –> males only typically
What is HGPRTase?
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
What would a nucleotide rich diet consist of?
Testes and Thymus
