Nucleotide Catabolism

Question 1

Describe the ring structure of Purine

Answer 1

double ring (adenine and guanine)

Question 2

Describe the ring structure of Pyrimidine

Answer 2

single ring (cytosine, uracil, thymine)

Question 3

What are nucleotides broken down to?

Answer 3

Base, Ribose, Phosphate

Question 4

Do you absorb ATP from nucleotides?

Answer 4

No! You absorb the components of nucleotides

Question 5

What are nucleosides broken down to?

Answer 5

Base, Ribose

Question 6

What can Pyrimidines eventually be catabolized to?

Answer 6

CO2, H2O, NH3, recycle the ring

Question 7

What is thymine catabolized into?

Answer 7

β-aminoisobutyrate -> Propionyl CoA -> Succinyl-CoA

• anapleurotic for TCA
• potentially glucogenic

Question 8

What is cytosine catabolized into?

Answer 8

Cytosine -> Uracil -> β-alanine -> Acetyl CoA

• fuel for TCA
• ketogenic (but a small source compared to fats)

Question 9

Where is the intermediate β-aminoisobutyrate found (BAIB)?

Answer 9

Thymine catabolism

Question 10

What do increased levels of β-aminoisobutyrate (BAIB) in the blood mean?

Answer 10

Indicator of Cancer and excess cell death

Question 11

Where is the intermediate β-alanine found?

Answer 11

Cytosine catabolism

Question 12

β-aminoisobutyrate and β-alanine are structurally related to what to what compounds?

Answer 12

GABA and Glycine

Question 13

An enzyme deficiency in the Thymine or Cytosine catabolism pathways might result in what clinical symptom?

Answer 13

Neurological problems because you have too much or too little of inhibitory transmitters (GABA and Glycine)

Question 14

How is Purine catabolized?

Answer 14

Purine -> Uric Acid -> Renal Filtrate -> Resorption -> Back to Liver -> Uric Acid -> Allantoin -> Excreted in Urine

Question 15

What animals excrete Uric Acid?

Answer 15

Primates, Dalmatians, Fish, Birds, Lizards, Insects (through their urine)

Question 16

What animals excrete Allantoin?

Answer 16

Most Mammals (through their urine)

Question 17

What animals excrete Allantoic Acid?

Answer 17

Bony Fish, through their gills

Question 18

What animals excrete Glycoxylate and Urea?

Answer 18

Amphibians and Cartilaginous Fish, through their urine

Question 19

How much energy comes from Purine Catabolism?

Answer 19

NONE! No energy is captured, No carbons are converted into fuel. Cannot get energy from double ringed Purines, only from ribose sugars in HMPS

Question 20

What compounds in the Purine catabolism pathway are soluble and poorly soluble?

Answer 20

Soluble: Allantoin

Poorly Soluble: Uric Acid (forms crystals/precipitates in aq solution)

Question 21

How many steps is the liver involved in with purine catabolism?

Answer 21

2 steps. Must make 2 trips to the liver

Question 22

What are the steps in purine degradation of GMP?

Answer 22

GMP -> take off P, have Guanosine -> take off sugar, have Guanine -> take off amino group, have Xanthine

Question 23

What are the steps in purine degradation of IMP?

Answer 23

IMP -> take off P, have Inosine -> take off sugar, have Hypoxanthine -> oxidize, have Xanthine

Question 24

What are the steps in purine degradation of AMP?

Answer 24

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

Question 25

What happens to Xanthine?

Answer 25

Xanthine is oxidized again -> Uric Acid -> Urate

Question 26

How many pathways generate Xanthine?

Answer 26

3! From AMP and IMP (by way of hypoxanthine) and GMP (from Guanine)

Question 27

What clinical problems will result from Adenosine deaminase (ADA) deficiency/defect?

Answer 27

Immuno deficiency of B and T cells, SCID, Bubble Boy

-adenosine accumulates, and shutting off nucleotide synthesis

Question 28

What clinical problems will result from Phosphorylase deficiency/defect?

Answer 28

T cell deficiency, SCID

• will have an equal accumulation of all 3 Adenosine, Inosine, and Guanosine
• pyrimidine synthesis blocked

Question 29

What clinical problems will result from Xanthine oxidase deficiency/defect?

Answer 29

Gout and Kidney/bladder stones

-same enzyme does 2 steps: Hypoxanthine -> Xanthine, and Xanthine -> Uric Acid

Question 30

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?

Answer 30

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)

Question 31

How can Xanthine Oxidase be blocked? Why would you want to block this enzyme?

Answer 31

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)

Question 32

What does HPGRTase do?

Answer 32

It is a “salvage pathway” that takes purine rings and reattaches ribose-5-P from PRPP to form IMP

Question 33

What clinical signs manifest in patients with Lesch-Nyhan Syndrome

Answer 33

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)