Disorders associated with Urea cycle

Question 1

Hyperammonemia

Answer 1

high levels of ammonia within the liver when it is unable to synthesize urea

Question 2

Urea cycle disorders characteristics

Answer 2

-hyperammonemia
-encephalopathy (brain dysfunction)
-respiratory alkalosis

Question 3

Most severe urea cycle disorders

Answer 3

-result in accumulation of precursors of urea, specifically ammonia and glutamine

most severe when blockages occur at the first 2 reactions of the urea cycle

Question 4

Hepatic encephalopathies

Answer 4

the most obvious sign of hyperammonemia

Question 5

What causes encephalopathies?

Answer 5

-too much nitrogen fiven to animal
-liver failure for any reason
-portal systemic shunt (blood passes by the liver) by congenital or acquired shunts, extrahepatic and intrahepatic
-urea cycle defects- the enzymatic pathway that produces urea is not functioning

Question 6

Ammonia observation in blood

Answer 6

-ammonia levels had to measure because they are unstable. Artifacts may occur due to delayed sample submission or from high protein meals or strenuous exercise

Question 7

Decreased levels of ammonia observed:

Answer 7

> decreased uptake of ammonia (hepatic blood flow abnormalities, hepatic dysfunction)
decreased conversions to urea (hepatic dysfunction, inherited disorders, lack of urea cycle intermediates, organic acidemias affecting urea cycle enzymes)

Question 8

Increased production of ammonia

Answer 8

-excessive growth of urease-producing enzymes in GIT
-Toxicity (poisoning with anhydrous ammonia, urea toxicity in cattle)

Question 9

Hepatic coma

Answer 9

-Ammonium inhibits channel and transporters (K channels, Na/K ATPase). An increased glutamine production to remove the ammonium results in acidosis and lack of energy.

-Ammonium also stimulates glycolysis which contributes to CNS acidosis

Question 10

Detoxification of ammonia as Uric acid

Answer 10

Uric acid is used by birds and reptiles to remove ammonia

-has low water solubility at low pH
-very high N by weight (33%)

Question 11

Formation of uric acid

Answer 11

1.degradation of purine nucleotides (RNA, DNA)
2. synthesis from bicarbonate and ammonia

Question 12

Ammonia and bicarbonate synthesis of uric acid

Answer 12

**main metabolic pathway used by birds

1. Ammonium incorporated into glutamine, aspartate, glycine
2. AAs react with bicarbonate and formyl-tetrahydrofolate in the cytosol to form purines
   3.Adenosine and guanosine are oxidized to xanthine and uric acid in the cytosol

Question 13

Allantoin production

Answer 13

Uricase converts uric acid to the safer allantoin.

**needed to ensure no build up in tissues occurs

Question 14

Energy requirements for Uric acid

Answer 14

-4 mol NH4 into 1 mol uric acid requires 19.5 mol ATP if adenosine is intermediate
OR 18.5 mol ATP if guanosine is intermediate

Question 15

What does the higher ATP requirements for uric acid mean for birds?

Answer 15

-allows birds to maintain higher body temperature
-conserves water
-maintain a low body weight
-uric acid scavenges O2 and reduces free radicals

Question 16

Uric acid in dalmations

Answer 16

-recessive trait in dalmations
-due to loss of GLUT 9 gene, urate transport in the liver and proximal tubules in the kidney is lost and allatonin does not get produced
>excretion equals or exceeds glomerular filtration= hyperuricosuria

**advised to give dalmations a low purine diet because purines contain uric acid and these dogs don’t have the ability to filter and convert it