2. Ammonia elimination

Question 1

What are the sources of ammonia in the ornithine cycle?

Answer 1

1. Intestinal glutaminase, urease
2. Hepatic transdeamination
3. Hepatic purine nucleotide cycle
4. Hepatic direct deamination (Ser, Gly, Thr, His, AA oxidases)

Question 2

Ammonia and ammonium ion
-> Which one is readily absorbed?

Answer 2

Ammonia

Question 3

How is the absorption of ammonia affected by pH?

Answer 3

Decreasing pH decreases the absorption of ammonia

Question 4

Locations of high activity of purine nucleotide cycle

Answer 4

Muscle and brain

Question 5

What is the net reaction of purine nucleotide cycle?

Answer 5

Asp deamination – fumarate – indirect deamination

Question 6

What is the aim of purine nucleotide cycle?

Answer 6

Ammonia for Gln synthesis for the kidney.

Question 7

Fumarate : anaplerotic for which cycle?

Answer 7

the citrate cycle

Question 8

Asp amino group is funelled into the nucleotide (IMP)
=> Which substances are formed.

Answer 8

AMP and fumarate

Question 9

Ornithine (Urea) cycle
-> Identify 1 - 5

Answer 9

Question 10

Is Arg always converted into urea? Why?

Answer 10

Arg is not necessarily converted into urea, Arg can be used for other reactions as well (later).

Question 11

If the cycle is for Arg synthesis (not for urea synthesis), e.g. in fast protein synthesis, then Arg must be suplied with ___

Answer 11

food.

Question 12

What is the enzyme involving in Allosteric regulation of the ornithin cycle?

Answer 12

Carbamoylphosphate Synthetase by N-acetylglutamate

Question 13

What is the localization of Allosteric regulation of the ornithin cycle? (Carbamoylphosphate Synthetase by N-acetylglutamate)

Answer 13

mitochondria

Question 14

What is the activator of CPS1?

Answer 14

N-acetyl-glutamate

Question 15

Production of N-acetyl-glutamate is stimulated by ____

Answer 15

dietary Arg (Arg) is also a direct precursor of urea in the cycle)

Question 16

CPS1 activity increases both with ____ (2 CONDITIONS)

Answer 16

protein-rich food and in starvation

Question 17

Glucagon prevents the exit of ___ from the mitochondria.

Answer 17

N-acetylglutamate

Question 18

Does allosteric regulation of the ornithin cycle have product inhibition?

Answer 18

No

Question 19

Fumarate produced by the urea cycle can regenerate ____ via enzymes involved in the tricarboxylic acid (TCA) cycle

Answer 19

aspartate

Question 20

Fumarate produced by the urea cycle can regenerate aspartate via enzymes involved in ____ (which cycle?)

Answer 20

the tricarboxylic acid (TCA) cycle

Question 21

Which organ produces Arg?

Answer 21

Gut-kidney axis

Question 22

Citrulline synthesis in __ (which organ?)

Answer 22

the intestine

Question 23

Arg is produced from citrulline in ___ (which organ?)

Answer 23

the kidney

Question 24

What happen to production of Arg if there is small intestine or kidney damage?

Answer 24

less Arg is synthesized than needed. Arg - essential AS.

Question 25

Long term regulation (transcriptional and regulation with sirtuin-deacetilation)

Answer 25

1. Fasting, protein rich food, but also high cortisol levels and cAMP increases the transcription of urea cycle enzymes 2. Sirtuins: NAD dependent deacetylases: Deacetylated CPS, OTC - active 3. SIRT-5 deacetylates and activates CPS, SIRT-3 – OTC.

Question 26

The role of SIRT-5

Answer 26

SIRT-5 deacetylates and activates CPS, SIRT-3 – OTC.

Question 27

What is the deffect in type I hyperammonemia?

Answer 27

deffect: carbamoyl phosphate synthetase

Question 28

What is the deffect in type II hyperammonemia?

Answer 28

deffect: ornithine transcarbamoylase

Question 29

What are transporter deficiencies in Hyperammonemia?

Answer 29

+ transporter deficiencies – ORNT1 (Orn/Citr exchanger), CITRlN (Asp/Glu exchanger)

Question 30

Name of these syntheses?

Answer 30

Question 31

# Metabolism of ammonia in the periportal and pericentral hepatocytes Periportal hepatocytes: urea cycle eliminates ___ (percentage) of NH3

Answer 31

70%

Question 32

# Metabolism of ammonia in the periportal and pericentral hepatocytes Periportal hepatocytes: urea cycle eliminates 70% of NH3 => rest of NH3 will become ___

Answer 32

substrate of Gln synthetase

Question 33

What are the 2 possibilities of incorporation of free ammonia in the liver?

Answer 33

1: Ornithine cycle CP synthetase reaction (ATP) 2: Glutamine synthetase (ATP)

Question 34

# Special role of Gln in the metabolism ___ (g?) Gln/day is metabolized

Answer 34

100

Question 35

What are the sources of Gln?

Answer 35

- Food: only 50% gets into the circulation - Muscle: 80g

Question 36

Ammonia is transported in the form of ___ in the blood

Answer 36

Gln

Question 37

____ (percentage) of the total amino acids in the blood is Gln

Answer 37

25%

Question 38

Glutamine 1. Mainly from ___ 2. Mainly serve for ___

Answer 38

1. Muscle, degradation of BBCA 2. Energy

Question 39

# Ammonia elimination in the brain The high ammonia cc. (hyperammonemia) puts a huge strain on ____ (which reactions?), especially in the brain.

Answer 39

ammonia-eliminating reactions

Question 40

What are The possibilities of elimination in the brain?

Answer 40

Glutamine synthetase Glutamate dehydrogenase

Question 41

# Ammonia elimination in the brain α-Ketoglutarate is used up to reduce ___

Answer 41

The ammonia, the citrate cycle is exhausted, the ATP level is low: fatigue, coma

Question 42

What are some therapies for Brain oedema?

Answer 42

- Osmolytes against brain oedema - Inhibit N-Absorption in the gut – Lactulose ( not digested disacharid, gives protons) - Antibiotics to inhibit bacteria in the gut - Synthetic products to eliminate NH3: biotransformation - Arginine or Ornithine to complete the cycle.

Question 43

What happen during acidosis?

Answer 43

the ornithine cycle slows down, less HCO3 is used, NH3 – NH4+. – CPS1 reaction is inhibited, NAG synthesis and glutaminase slow down, more ammonia enters the pericentral hepatocytes. More Gln comes out of the liver - into the kidneys.