Purine Biosyn

Question 1

What is the difference between a nucleoSide and a nucleoTide?

Answer 1

• Side: base + sugar

- Tide: base + sugar + phosphate

Question 2

First step of purine biosynthesis?

Answer 2

Ribose 5-phophate uses PRPP synthetase, and is converted to PRPP

PRPP is the active form of ribose, for nucleotide synthesis

Question 3

Second (committed) step of purine biosyn?

Answer 3

PRPP + glutamine = phosphoribosylamine (PRA)

Question 4

Third step?

Answer 4

Phosphoribosylamine + glycine -> GAR

Question 5

Steps after the third?

Answer 5

GAR -> FGAR -> FGAM -> AIR -> CAIR -> SACAIR -> AICAR -> FAICAR

Question 6

Step after formation of FAICAR?

Answer 6

FAICAR -> Inosine monophosphate (IMP)

Question 7

IMP becomes ___ and ___

Answer 7

GMP and AMP, which go to GDP -> GTP and ADP -> ATP, respectively.

GDP and ADP can both inhibit PRPP synthase, leading to less PRPP being produced, from R-5-P

Question 8

Synthesis of AMP requires (ATP or GTP)?

Synthesis of GMP requires (ATP or GTP)?

Answer 8

AMP needs GTP

GMP needs ATP

Question 9

Tetrahydrofolate characteristics?

Answer 9

Is the active form of folic acid

Sulfonamides and methotrexate inhibit THF synthesis

Question 10

Methotrexate characteristics?

Answer 10

Inhibits dihydrofolate reductase (THF cannot be formed, from folic acid)

Inhibits nucleotide synthesis for DNA and RNA synthesis

Question 11

Sulfonamide characteristics?

Answer 11

Competitive inhibitors of folate synthesis

Question 12

What two enzymes are used in the purine nucleotide salvage pathway?

Answer 12

Hypoxanthine and guanine use HGPRT to become IMP and GMP, respectively

Adenine uses adenine phosphoribosyltransferase (APRT) to become AMP

Question 13

What occurs if APRT, the adenine salvage enzyme, is deficient?

Answer 13

If APRT is deficient, adenine cannot become AMP; adenine accumulates.

Increase adenine will lead to an increase in DHA; too much DHA forms insoluble crystals in urine (stones)

Tx of too much DHA? Allopurinol

Question 14

What is the point of salvage pathways?

Answer 14

They reduce the amount of PRPP; this would then slow the de novo pathway

Question 15

Hyperuricemia may be a result of:

Answer 15

Increased purine degradation

Decreased uric acid clearance by the kidneys

Increased dietary intake of purines

Tx: allopurinol (inhibitor of xanthine oxidase)

Question 16

Xanthine oxidase characteristics?

Answer 16

Generates hydrogen peroxide and superoxide

Is inhibited by allopurinol

Question 17

Role of allopurinol?

Answer 17

Is a suicide inhibitor of XO

Decreases uric acid because it allows hypoxanthine and xanthine to be more soluble (and more able to be urinated out)

Question 18

Gout characteristics?

Answer 18

Characterized by hyperuricemia

Occurs more in diets consisting of meats and alcohol

Caused by: too much purine turnover or the inability to excrete uric acid (too much stays in the body)

Tx: colchicine, allopurinol

Question 19

Lesch-Nyhan syndrome characteristics?

Answer 19

Caused by mutations of the HPRT enzyme (salvage pathway!)

Hypoxanthine and guanine are not salvaged, so PRPP is not used (it would be used to convert those two to IMP and GMP)

If Hypoxanthine and guanine continue normally, they become uric acid.

Because PRPP is not used here, it will be used in the purine synthesis pathway; an increase in purines (hypoxanthine and guanine) will increase uric acid in the blood (hyperuricemia)

Question 20

Adenosine deaminase deficiency characteristics?

Answer 20

Is one form of SCIDS

Deoxyadenosine (dA) needs ADA to become deoxyinosine, to proceed normally. Because ADA is deficient, dA accumulates

Elevated dA (and thus dATP) inhibits ribonucleotide reductase, which prevents the formation of other dNTPs

Therefore, no DNA can be synthesized, so no T / B / NK cells can be produced