Uric acid metabolism

Question 1

What are the three main purines?

Answer 1

Adenosine
Guanosine
Inosine

Question 2

What are the key roles of purines?

Answer 2

Genetic code (A, G)
Messengers for hormone action (cAMP, cGMP)
Energy transfer (ATP)

Question 3

What enzyme breaks down hypoxanthine to xanthine?

Answer 3

Xanthine oxidase

Question 4

What enzyme breaks down xanthine to urate?

Answer 4

Xanthine oxidase

Question 5

What enzyme breaks down urate to allantoin?

Answer 5

Uricase

Question 6

Which gender is gout more common in?

Answer 6

Males

Question 7

Which enzyme in the urate metabolism process is inactive in humans?

Answer 7

URICASE

this means there is a buildup of urate

Question 8

What concentration does urate circulate at in blood?

Answer 8

At the limit of solubility

Urate is INSOLUBLE

Question 9

How does solubility of urate change based on temperature?

Answer 9

At colder temperatures, solubility DECREASES

Question 10

What is the most commonly affected joint in gout? Why?

Answer 10

First metatarsophalangeal joint

Because it is at the extremity of the body > colder > urate is more likely to precipitate

Question 11

Is urate reabsorbed/secreted by the kidney?

Answer 11

BOTH occur in the PCT
Only 10% of urate is filtered our
This is why urate concentration is so high

Question 12

What is the fractional excretion of uric acid (FEUA)?

Answer 12

The fraction of filtered urate

The urate present in urine, so 10%

Question 13

What are the two pathways for purine synthesis?

Answer 13

De novo purine metabolism

Salvage pathway

Question 14

Compare metabolic demands of the two pathways for purine synthesis

Answer 14

De novo - VERY metabolic demanding, inefficient

Salvage - highly energy efficient

Question 15

Which purine pathway predominates?

Answer 15

SALVAGE pathway

Question 16

Where does the de novo pathway predominate?

Answer 16

in the bone marrow

due to high requirements

Question 17

What is the rate limiting enzyme for the de novo pathway?

Answer 17

PAT

Question 18

What exerts negative / positive feedback on PAT?

Answer 18

Neg feedback: AMP, GMP

Positive feedback: PPRP

Question 19

What is the rate limiting enzyme in salvage pathway?

Answer 19

HPRT

Question 20

What is Lesch–Nyhan syndrome?

Answer 20

ABSOLUTE DEFICIENCY in HGPRT

Question 21

What is the method of vertical transmission of LNS?

Answer 21

X linked recessive

Question 22

What are clinical features of LNS?

Answer 22

Normal at birth 
Development delay at 6m
Hyperuricaemia 
Choreiform movements 
Spasticity, mental retardation 
SELF HARM

Question 23

What is the biochemical basis of LNS?

Answer 23

Lack of HPRT > guanine not converted back to GMP > no GMP, AMP > no negative feedback

Also PPRP buildup

Overall, sends de novo pathway into overdrive

Question 24

What are causes of secondary hyperuricaemia due to increased urate production? Why

Answer 24

Conditions lke Myeloproliferative disorders, Lyphoprolif disorders

Because there is an increase in cell turnover > excess urate > inability to excrete urate last enough

Question 25

What toxin can cause gout?^

Answer 25

LEAD poisoning causes saturnine gout

Question 26

What drug can cause gout?

Answer 26

Diuretics, due to decreased urate excretion

Question 27

What kind of crystals form in gout?

Answer 27

monosodium urate

Question 28

What is the shape of crystals in gout?

Answer 28

needle shaped

Question 29

What are the two diseases u can get from gout?

Answer 29

PODAGRA - acute TOPHACEOUS gout - chronic

Question 30

What are clinical features of gout?

Answer 30

Rapid build up of pain Hot swollen painful joint Typically 1st MTP (first to appear, most common)

Question 31

How do gout crystals show up in polarised light?

Answer 31

``` NEGATIVE BIOREFRINGENCE (so perpendicular to compensator axis) and BLUE Parallel to compensator if YELLOW ```

Question 32

How do pseudogout crystals show up in polarised light?

Answer 32

POSITIVE BIOREFRINGENCE (blue and parallel to compensator)

Question 33

What substance are pseudo gout crystals made up of?

Answer 33

calcium pyrophosphate

Question 34

What tx work for acute gout?

Answer 34

NSAID Colchicine Glujcocorticoid

Question 35

What tx works for chronic gout=?

Answer 35

Allopurinol | Probenecid

Question 36

What kind of medication is allopurinol?

Answer 36

XANTHINE OXIDASE inhibitor | so reduces urate synthesis

Question 37

What medication must you never give with allopurinol?

Answer 37

AZATHIOPRINE BECAUSE azathioprine is toxic to BM at high doses Allopurinol blocks mercaptopurine secretion (mercaptopurine is product of azathioprine) thereby massively increasing its effecxt

Question 38

What is the MOA of probenecid ?

Answer 38

URICOSURIC drug | increases secretion of urate in urine (increases FEUA)

Question 39

describe what occurs in pseudogout

Answer 39

in patients with osteoarthritis | deposition of calcium pyrophorphate crystals