Nucleotide Catabolism Flashcards
Describe the ring structure of Purine
double ring (adenine and guanine)
Describe the ring structure of Pyrimidine
single ring (cytosine, uracil, thymine)
What are nucleotides broken down to?
Base, Ribose, Phosphate
Do you absorb ATP from nucleotides?
No! You absorb the components of nucleotides
What are nucleosides broken down to?
Base, Ribose
What can Pyrimidines eventually be catabolized to?
CO2, H2O, NH3, recycle the ring
What is thymine catabolized into?
β-aminoisobutyrate -> Propionyl CoA -> Succinyl-CoA
- anapleurotic for TCA
- potentially glucogenic
What is cytosine catabolized into?
Cytosine -> Uracil -> β-alanine -> Acetyl CoA
- fuel for TCA
- ketogenic (but a small source compared to fats)
Where is the intermediate β-aminoisobutyrate found (BAIB)?
Thymine catabolism
What do increased levels of β-aminoisobutyrate (BAIB) in the blood mean?
Indicator of Cancer and excess cell death
Where is the intermediate β-alanine found?
Cytosine catabolism
β-aminoisobutyrate and β-alanine are structurally related to what to what compounds?
GABA and Glycine
An enzyme deficiency in the Thymine or Cytosine catabolism pathways might result in what clinical symptom?
Neurological problems because you have too much or too little of inhibitory transmitters (GABA and Glycine)
How is Purine catabolized?
Purine -> Uric Acid -> Renal Filtrate -> Resorption -> Back to Liver -> Uric Acid -> Allantoin -> Excreted in Urine
What animals excrete Uric Acid?
Primates, Dalmatians, Fish, Birds, Lizards, Insects (through their urine)
What animals excrete Allantoin?
Most Mammals (through their urine)
What animals excrete Allantoic Acid?
Bony Fish, through their gills
What animals excrete Glycoxylate and Urea?
Amphibians and Cartilaginous Fish, through their urine
How much energy comes from Purine Catabolism?
NONE! No energy is captured, No carbons are converted into fuel. Cannot get energy from double ringed Purines, only from ribose sugars in HMPS
What compounds in the Purine catabolism pathway are soluble and poorly soluble?
Soluble: Allantoin
Poorly Soluble: Uric Acid (forms crystals/precipitates in aq solution)
How many steps is the liver involved in with purine catabolism?
2 steps. Must make 2 trips to the liver
What are the steps in purine degradation of GMP?
GMP -> take off P, have Guanosine -> take off sugar, have Guanine -> take off amino group, have Xanthine
What are the steps in purine degradation of IMP?
IMP -> take off P, have Inosine -> take off sugar, have Hypoxanthine -> oxidize, have Xanthine
What are the steps in purine degradation of AMP?
AMP can go two ways:
either to IMP or AMP -> take off P, have Adenosine -> take off sugar, have Adenine -> take off amino group, have Hypoxanthine -> oxidize, have Xanthine
What happens to Xanthine?
Xanthine is oxidized again -> Uric Acid -> Urate
How many pathways generate Xanthine?
3! From AMP and IMP (by way of hypoxanthine) and GMP (from Guanine)
What clinical problems will result from Adenosine deaminase (ADA) deficiency/defect?
Immuno deficiency of B and T cells, SCID, Bubble Boy
-adenosine accumulates, and shutting off nucleotide synthesis
What clinical problems will result from Phosphorylase deficiency/defect?
T cell deficiency, SCID
- will have an equal accumulation of all 3 Adenosine, Inosine, and Guanosine
- pyrimidine synthesis blocked
What clinical problems will result from Xanthine oxidase deficiency/defect?
Gout and Kidney/bladder stones
-same enzyme does 2 steps: Hypoxanthine -> Xanthine, and Xanthine -> Uric Acid
What clinical problems will result from a HPGRTase deficiency/defect?
What happens when Hypoxanthine and Guanine can’t get recycled to PPRP with the enzyme HPGRTase?
Lesch-Nyhan Syndrome
-IMP + PPi are made. Hypoxanthine and Guanine can’t get recycled to PPRP, the sugar and P are not put back on to make nucleotides, have a build up or uric acid (gout)
How can Xanthine Oxidase be blocked? Why would you want to block this enzyme?
The drug: Allopurinol and/or Purine poor diet for the treatment of Gout
- Won’t make Uric Acid (which is made into allantoin in most mammals)
- In people or dalmatians you can block Uric Acid production and have Xanthine and Hypoxanthine as your products (which are more soluble, but not excreted as easily)
What does HPGRTase do?
It is a “salvage pathway” that takes purine rings and reattaches ribose-5-P from PRPP to form IMP
What clinical signs manifest in patients with Lesch-Nyhan Syndrome
Neuro disorder that results in self mutilation. Shows up in males. Cannot recycle purines. Have unsocial behavior. GTP accumulates, screws up dopamine production. Crystals of uric acid precipitate throughout body (including in the brain)