4- purine nucleotide metabolism

Question 1

What are nucleotides ?

Answer 1

They are purines and pyrimidines

Question 2

What are the two purins ?

Answer 2

Adenine , guanine

Question 3

What are the three pyrimidins ?

Answer 3

Cytosine, thymine and uracil

Question 4

What are the 5 function of nucleotides ?

Answer 4

1- purines and pyrimidines are the basic units of nucleic acid ( like DNA and RNA ).
2- essential carriers of chemical energy ( ATP and GTP ).
3- Components of the cofactors - NAD+, NADP+, FAD, S-adenosy methionine, Coenzyme A.
4- Signalling molecules; Cyclic nucleotides: CAMP, GMP.
5- Biosynthetic intermediates; UDP-Glucose, CDP-diacylglycerol.

Question 5

What is the major site for the synthesis of purines ?

Answer 5

The liver

Question 6

What dose purine biosynthesis start with ?

Answer 6

PRPP ( 5-Phospho-D-Ribosyl-1-PyroPhosphate )

Question 7

What is utilized in biosynthesis of purines ?

Answer 7

5 ATP, 2 Gln, 1 Gly, 1 CO2, 1 Asp and 2 HCOOH

Question 8

Where is inosine monophosphate (IMP) is synthesized ?

Answer 8

At the end of 10 consecutive reactions in a purine nucleotide

Question 9

What is required both for the de novo synthesis and the recycling pathways ?

Answer 9

PRPP because it donates the ribose part of the purine nucleotides

Question 10

What are the two sources of ribose 5-phosphate ?

Answer 10

1- pentose phosphate pathway .
2- phosphorolysis of nucleosides by nucleoside phosphorylase

Question 11

What are the 4 limiting (control) steps in de novo purine biosynthesis ?

Answer 11

1- PRPP synthetase
2- Glutamine-PRPP amidotransferase
3- Adenylosuccinate synthetase
4- IMP dehydrogenase

Question 12

What is phosphoribosyltransferases ?

Answer 12

They are the the bases ( adenine, hypoxanthine, guanine) taken in from the diet or released from nucleic acid breakdown, they are converted to purine nucleotides.

Question 13

What is the phosphoribosylation of bases ?

Answer 13

It is the reaction mechanism of phosphoribosyltransferasses in purine

Question 14

What is formed as the end product of the degradation of nucleotides ?

Answer 14

Uric acid

Question 15

What is the clinical importance of purine nucleotide metabolism ?

Answer 15

1- The most of the diseases are related to degradation .
2- deficiencies might result in mild, acute and fatal consequences.
3- gout, lesch-nylan and SCID.

Question 16

What is Gout ?

Answer 16

It is a disease of the joins caused by an elevated concentration of uric acid in the blood (Hyperuricemia)
and tissues

Question 17

What happens to the joints in when the patient has gouts ?

Answer 17

The joints become inflamed, painful and arthritic, owing to the abnormal deposition of sodium urate crystals.

Question 18

Why is the kidney is also affected by gouts ?

Answer 18

excess uric acid is deposited in the kidney tubules.

Question 19

In which gender is gouts is predominant ?

Answer 19

In males

Question 20

What are the three molecular basis of hyperuricemia ?

Answer 20

1- Increase in PRPP synthetase activity will result in increased
[PRPP], in turn, PRPP will activate Gln-PRPP amidotransferase
(de novo synthesis will increase)
ii. Deficiency of Glucose 6-phosphatase; Diversion of glucose
phosphates to PPP
iii. Mutations in HGPRT will result in decreased activity of the
recycling pathway, Unused PRPP in cells, in turn, will activate Gln-PRPP amidotransferase

Question 21

What is the nutritional treatment of gout ?

Answer 21

Decrease Intake of nucleic acid rich diet such as meat, cheese .

Question 22

What is the drug therapy treatment for gout ?

Answer 22

Allopurinol (an analogue
of hypoxanthine) is an inhibitor of
xanthine oxidase so, degradation of
purines will stop at the hypoxanthine and
xanthine steps. Hypoxanthine and
Xanthine is much soluble in water than
uric acid and also they have no tendency
to form crystals.

Question 23

What are the complication with gout ?

Answer 23

1- stroke
2- heart failure
3- Acute myocardial infarction
4- Renal damage by hypertension
5- Hyperuricaemic nephropathy
6- Urate stones

Question 24

What is the cause of lesch-nyhan syndrome ?

Answer 24

Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency

Question 25

What are the symptoms of lesch-nyhan syndrome ?

Answer 25

-Nervous system defects
- Mental deficiency and spasticity
- Self-destructive behavior (eating fingers, toes and lips)
- Hypoxhanthine and guanine arise constantly from the breakdown of
nucleic acids.

Question 26

What is the cause of SCID ?

Answer 26

ADA (adenosine deaminase) deficiency

Question 27

What is. The symptoms of SCID ?

Answer 27

-T and B lymphocytes do not develop properly.
- Lack of ADA leads to a 100-fold increase in the cellular concentration of dATP.
- High [dATP] will inhibit ribonucleotide reductase, result in a general deficiency
of other dNTPs in T – lymphocytes
- Individuals with ADA deficiency lack an effective immune system and do not
survive unless in a sterile “bubble” environment.

Question 28

How is SCID treated ?

Answer 28

• Bone marrow transplantation
• red blood cells transfusion
• enzyme (ADA) replacement therapy
• gene therapy