Nitrogen metabolism: protein breakdown and the urea cycle

Question 1

How are amino acids stored?

Answer 1

They aren’t stored!

Question 2

What 3 ways do we obtain amino acids?

Answer 2

Diet
De novo synthesis
Recovered from protein degradation

Question 3

What is the removal of an amino group called?

Answer 3

Catabolism

Question 4

What are the 2 phases of catabolism?

Answer 4

1. alpha - Amino group removal

2. alpha - keto acids converted to intermediates

Question 5

How does the 1st phase of catabolism occur and what does it produce?

Answer 5

Transamination –> oxidative deamination

Forms ammonia and alpha-keto acid

Question 6

How does the 2nd phase of catabolism occur and what does it produce?

Answer 6

Metabolism

CO2, H2O, glucose, fatty acids and keto acids are formed

Question 7

How does nitrogen enter and leave the body?

Answer 7

Enters: Many forms like diet
Leaves: Urea and ammonia

Question 8

What is the amino acid pool supplied by? (3)

Answer 8

AA from degraded body proteins
AA from dietary proteins
Synthesis of non-essential amino acids from simple intermediates

Question 9

How is the Amino acid pool depleted? (3)

Answer 9

Protein synthesis
Nitrogen-containing molecule precursors
Conversion to glucose, glycogen, fatty acids etc

Question 10

How many grams of AA are in cells and blood?

Answer 10

100g

Question 11

How many grams of protein are hydrolysed & resynthesises each day?

Answer 11

300-400g

Question 12

How do we degrade protein?

Answer 12

1. ATP-dependent ubiquitin-proteasome (endogenous proteins)

2. ATP-independent enzyme system of the lysosome (extracellular proteins)

Question 13

Give an example of a protein that needs regular turnover and protein that has a low turnover until needed:

Answer 13

Regular turnover: keratin

Low turnover until needed: Antibodies

Question 14

What is the ubiquitin-proteasome proteolytic pathway? (3)

Answer 14

1. Protein is selected for degradation is tagged with ubiquitin
2. Ubiquinated proteins are recognised by cytosolic proteasome - transports to proteolytic core
3. Peptide fragments produced by the proteasome are degraded to A.A. in the cytosol

Question 15

Where are proteins digested? (3)

Answer 15

Degraded by enzymes in the small intestine, pancreas and stomach

Too big to ingested by intestine

Question 16

How are proteins digested?

Answer 16

Stomach - gastric juice (HCl: denatures, Pepsin: endopeptidase cuts proteins from sequence)

Pancreas - produces proteases (trypsin)

Question 17

Where and how are amino acids absorbed? (4)

Answer 17

Small intestine

• Aminopeptidase produces smaller peptides and free AA
• Free AA taken into enterocytes by Na+ system
• Di/Tri peptides are taken up into enterocytes by H+ system

Question 18

How are amino acids transported into cells?

Answer 18

Concentration gradients

7 different transport systems that exist for AA

Question 19

What is vital for catabolism of an Amino acid?

Answer 19

Removal of the alpha-amino group

Question 20

What is transamination?

Answer 20

Amino acid group transferred to glutamate (aa group donor)

Question 21

What does an amino acid become once the NH3+ group is removed?

Answer 21

Keto acid

Question 22

What are aminotransferases and where are they found?

Answer 22

Cytosol and mitochondria

Funnel amino ac id groups to oxaloacetate (nitrogen source in urea cycle)

Question 23

What are the 2 aminotransferases?

Answer 23

Alanine aminotransferase

Aspartate aminotransferase

Question 24

What is phase 1 of amino acid breakdown?
Where does it occur?
What else also undergoes this?

Answer 24

Oxidative deamination
Liver and kidney
Glutamate

Question 25

What is ureas role in amino acid breakdown?
Where is urea produced?
Where do reactions 1 and 2 of the urea cycle occur?
Where do the other steps occur?

Answer 25

Major disposal method of amino groups
Produced in the liver and transported to the kidneys
Mitochondrial matrix
The cytosol

Question 26

What are the 4 main steps of the urea cycle?

Answer 26

1. Citrulline (co-transports) moved by ornithine across the inner membrane
2. Arginiosuccinate formation uses the last molecule of ATP
3. Fumarate is hydrated to malate (NADH and ATP formed)
4. Arginase synthesises urea

Question 27

Why is urea synthesis irreversible?

Answer 27

4 high energy phosphate bonds are consumed

Question 28

What is the overall equation for the urea cycle?

Answer 28

Aspartate + NH3 + HCO3- + 3 ATP + H2O ===> urea + fumarate + 2 ADP + AMP + 2 Pi + PPi

Question 29

What happens when ammonia levels are too high? (6)

Answer 29

Tremors, speech slurring, drowsiness, blurred vision, coma, death

Question 30

Whats the affect of acquired hyperammonemia?

Answer 30

Liver diseases

Liver cirrhosis

Question 31

What is congenital hyperammonemia? (2)

Answer 31

Genetic deficiencies of urea cycle enzymes

High mortality rates

Question 32

What is phase 2 of amino acid breakdown?

Answer 32

Conversion of carbon skeletons

Question 33

What do the metabolic pathways that convert alpha-veto acids form and what do they result in? (7) + (3)

Answer 33

Oxaloacetate
Pyruvate
Alpha - ketogluarate
Fumerate
Succinyl coenzyme A
ACetyl CoA
Acetoacetate

Glucose
Lipid
Energy generation

Question 34

What are the 2 classes on amino acids? (3)

Answer 34

Glucogenic
Ketogenic
Both

Question 35

What is a glycogenic amino acid?

Answer 35

Catabolism yields pyruvate or TCA cycle

Substrate for gluceoneogensis

Question 36

What is a ketogenic amino acid?

Answer 36

Catabolism yields acetoacetate or acetyl CoA or acetoacetly CoA
Carbon skeletons cannot lead to glucose

Question 37

What is phenylketonuria?

Answer 37

Inborn erros of metabolism - mutant enzymes

Question 38

What causes phenylketonuria?

Answer 38

Deficiency of phenylalanine hydroxylase

Question 39

What are the symptoms of phenylketonuria? (3)

Answer 39

Intellectual disability, developmental delay, seizures