Topic 12: Urea Cycle

Question 1

Why is Urea Cycle a two-fer?

Answer 1

Get rid of Ammonia and CO2!
NH3 from AA break down
CO2 from natural action of Carbonic Anhydrase on CO2 and H2O in the blood to make the HCO3 (bicarb) used in Step 1 of the Urea Cycle

Question 2

Why is Ammonia/NH3 bad for you?

Answer 2

it readily passes membranes, enters the CNS, decreases pH –> alters CHARGES of proteins –> bad idea!
ALKALINIZES the body –> pH disturbances kill your proteins
CNS super duper susceptible

Question 3

How do animals that live in the sea excrete NH3?

Answer 3

just as NH3 and the surrounding water dilutes it out

Question 4

How do LAND animals excrete NH3?

Answer 4

NH3 is converted to UREA, out through kidneys

Question 5

How do birds excrete NH3?

Answer 5

as URIC ACID

Question 6

What would UP-REGULATE the UREA CYCLE?

Answer 6

High Protein Diet
Prolonged Fasting (proteolysis via heavy glucagon influence)

Question 7

What tissues can make Urea?

Answer 7

the LIVER!!!! ONLY the Liver!

NOTHING BUT THE LIVER!!!!@#(!&@#(&!

Question 8

Where does the Urea cycle take place? (besides in hepatocytes)

Answer 8

Partly in the Cytoplasm and Partly within mitochondria

Question 9

What is Step 1 of the Urea Cycle?

Answer 9

HCO3 + 2ATP (2 equivalents used) + NH4 –>via CPS-1 (Carbamoyl Phosphate Synthetase)–> Carbamoyl Phosphate

happens IN the mitochondria; Yields 2 ADP

Question 10

What is Step 2 of the Urea Cycle?

Answer 10

Carbamoyl Phosphate + Ornithine via Ornithine Transcarbamoylase make CITRULLINE

Free phosphate pulled off to power reaction

Question 11

What is Step 3 of the Urea Cycle?

Answer 11

Citrulline passes out to the cytosol via Ornithine/Citrulline Antiport

Citrulline via Argininosuccinate Synthetase is combined with Aspartate to make Argininosuccinate

Uses ATP –> AMP + 2Pi (2 equivalents worth)

Question 12

What is Step 4 of the Urea Cycle?

Answer 12

Argininosuccinate via Argininosuccinase makes Arginine (goes on) and Fumarate (back to TCA)

Question 13

What is Step 5 of the Urea Cycle?

Answer 13

Arginine via Arginase releases UREA!!! and Ornithine is regenerated!

Uses H2O

Question 14

How many ATP are used in the Urea Cycle?

Answer 14

4 ATP:
2 at Step 1
1 ATP at Step 3 used for 2 equivalents

Question 15

What goes into the mitochondria in the Urea Cycle?

Answer 15

Ornithine

Question 16

What goes out of the mitochondria in the Urea Cycle?

Answer 16

Citrulline

Question 17

What is something unique and ABSOLUTELY NECESSARY for the Urea Cycle to take place?

Answer 17

N-AcetylGlutamate –> activates CPS-1 (Step 1 of Urea Cycle)
Allosteric Activator of CPS-1

Acetyl-CoA + Glutamate = N-AcetylGlutamate

Question 18

Where would you expect to see the most dramatic effects of an Urea Cycle enzyme deficiency?

Answer 18

CNS SIGNS!

Also, respiratory due to alkalosis (slower breathing)

Question 19

How would you treat a urea cycle enzyme deficiency?

Answer 19

Carefully monitor Diet,
Drugs to lower blood ammonia,
Antibiotics against gut flora that metabolize Urea, releasing free ammonia back into the body

Question 20

What’s the difference between surgical treatment of an extra-hepatic PSS as opposed to an intra-hepatic PSS?

Answer 20

Extra-hepatic are easier to deal with surgically

Intra-hepatic are a bitch

Question 21

What are Portosystemic Shunts (PSS)?

Answer 21

Connections between the hepatic portal veins and the caudal vena cava

Question 22

What are results of a PSS?

Answer 22

CNS TOXICITY:
anorexia, depression, lethargy…hyperactivity, head-pressing, disorientation, temporary blindness, weakness, excess salivation, seizures, coma

vomiting, diarrhea, hematuria, tenesmus, PU/PD, fever, poor body condition, small stature

hahaha have fun memorizing that!

Question 23

What can cause/where do PSS come from?

Answer 23

1. Persisten Patent Ductus Venosus
2. Congenital or Genetic
3. Acquired

Question 24

How can you treat a PSS?

Answer 24

Surgery
OR
Low Protein/High Fiber Diet WITH Antibiotics

Question 25

What is a “side cycle” characteristic of the Urea Cycle not mentioned yet?

Answer 25

Regenerating ASPARTATE that needs to be combined with Citrulline to make Arginosuccinate.

Fumarate –> Malate (can go to Pyruvate Via Malic Enzyme if need be [NADP–>NADPH]) –> OAA –> Aspartate!!!

Question 26

What could potentially inhibit the Urea Cycle?

Answer 26

low pH (acidotic) inhibts Carbonic Anhydrase activity as well as Glutaminase

Question 27

What enzyme do bacteria have which allows them to metabolize Urea?

Answer 27

URICASE