Amino Acids/Urea Cycle

Question 1

Name an alpha keto acid used in muscle metabolism in aerobic conditions:

Answer 1

Pyruvate! (alpha keto acid of deaminated Alanine)

Question 2

How do amino acids get oxidized and where does this process take place?

Answer 2

AA lose their amino groups (NH3+) to form alpha keto acids which can be further oxidized to produce energy
In the liver cytosol!

Question 3

What are the enzymes responsible for catalyzing transaminations?

Answer 3

Aminotransferases

Question 4

How does the muscle deliver excess amines as ammonia ions to the liver for processing?

Answer 4

Alanine (which is transaminated to pyruvate)

Question 5

Which amino acid contains 2 amine groups in its structure, Q or E?

Answer 5

Q = Glutamine

Question 6

If Glutamine gives up 1 of its amine groups, what does it become? Where does the second amine group go?

Answer 6

Glutamate

Urea (as ammonium)

Question 7

What does glutamate indicate about our nitrogen metabolism?

Answer 7

Indicates intracellular levels of amine groups captured as NH4

Question 8

What does glutamine indicate about our nitrogen metabolism?

Answer 8

Indicates the extracellular levels of amine groups because the other tissues are getting rid of their excess amines as glutamine (excess amines collected from kidneys and intestines processed in the liver as glutamine and are excreted as urea)

Question 9

Which of the following amino acid metabolites is synthesized in the liver cytosol? 
A) Glutamine
B) Alpha-KG
C) Glutamate 
D) Glutamate dehydrogenase

Answer 9

C) Glutamate! Forms when an amino acid donates an amine group to alpha-KG

Question 10

Where in the liver cell does glutamate give up its amino group? Where does glutamine give up its amino group? Who are they giving it to?

Answer 10

Glutamate will enter the mitochondria and associate with glutamate DHase and in the process it will give up the amino group to form NH4
Glutamine will enter the mitochondria and will give up its amine groups to alpha ketoglutarate to form glutamate and subsequently associate with glutamate DHase

Question 11

Where are amino groups from amino acids transferred to alpha ketoglutarate?

Answer 11

Liver cytosol

Question 12

What cofactors are needed for transamination to occur? Would this be a prostethic group?

Answer 12

PLP (pyridoxal phosphate) co-factor

**Prostethic group b/c PLP is covalently bound to the aminotransferases active site through a Lys residue

Question 13

What does the aldehyde form of PLP do?

Answer 13

Forms and accepts the amino group

Question 14

What does the aminated form of PLP do?

Answer 14

Donates the amino group

Question 15

What are the 2 fates of amino acids that are processed in the liver?

Answer 15

1) Resulting alpha-keto acids can be further oxidized (i.e. pyruvate –> TCA –> ATP)
2) Eliminate NH4 as urea

Question 16

Which enzyme cataylzes oxidative deamination in the liver mitochondria?

Answer 16

Glutamate Dehydrogenase = reduces NAD+ to oxidize glutamate into alpha-ketoglutarate

Question 17

What are 3 products released from glutamate dehydrogenase?

Answer 17

1) alpha-KG
2) NH4+
3) NADH + H+

Question 18

How does glutamine transport NH4+ into the bloodstream?

Answer 18

NH4+ produced in the extrahepatic tissues is transported in the blood as glutamine
Glutamine is formed from Glu + NH4+ = Gln
via glutamine synthetase

Question 19

Why does glutamine synthetase utilize ATP in its catalytic mechanism?

Answer 19

Adenylylation

1) Adds an excellent leaving group (phosphoryl)
2) Enhances the electrophilicty of the carbonyl carbon on glutamate for NH4+ (nucleophile)

Question 20

What are the 2 fates of Gln entering the liver for processing?

Answer 20

1) Loses an amine group to become Glutamate (via aminotransferase) and another to form urea
2) Gln can transfer its alpha amino group to pyruvate to generate alanine

Question 21

Where are the 2 amino groups of urea coming from? Who donates them?

Answer 21

1) Carbamoyl phosphate

2) Aspartate

Question 22

For every 1 molecule of urea how many amine equivalents are leaving the body?

Answer 22

2!

Question 23

Which metabolites function in the “shunt” between urea cycle and TCA cycle?

Answer 23

Fumarate and OAA

Question 24

Which TCA cycle metabolite is produced as a byproduct of the urea cycle?

Answer 24

Fumarate

Question 25

Which enzyme of the urea cycle is accepting the NH4+ released by Glutamine?

Answer 25

Carbamoyl Phosphate Synthetase I

Question 26

What are the 6 major products that 20 catabolic pathways converge onto?

Answer 26

1) alpha-KG
2) Succinyl-CoA
3) Fumarate (urea cycle)
4) OAA
5) Pyruvate
6) Acetyl CoA