L8: Amino acid synthesis

Are amino acids stored in the body?

No

Is there a protein that has a sole function as a supply of amino acids for future use?

No

How is nitrogen obtained for human body?

Nitrogen enters the body mostly as amino acids in dietary proteins

How does nitrogen leave the body?

Nitrogoen leaves the body as Urea, Ammonia, and other products

Explain the concept of amino acid pool

It refers to the very small amount of free amino acids in body (90-100g). Whatever is removed has to be replaced (steady state).

Explain the concept of protein turnover

A constant synthesis and degradation of proteins in the body

• Why: To remove abnormal and unwanted proteins

Total amount of proteins in the body should remain constant

• Why: There is a need to replace short-lived proteins

What is the function of absorbed amino acids?

• Energy source

• Used for protein synthesis in the liver and other tissues

• Excess a.a. are converted to glycogen and triacylglycerols for storage

Is amino acid metabolism more complex than carbohydrate and lipid metabolism?

Yes.

Describe the general pathways for amino acid catabolism for C atoms and N atoms.

Amino acid is split into carbon rich and nitrogen rich molecules

Carbon atoms → Krebs cycle and acetyl CoA → CO2 + H2O → generate energy

Nitrogen atoms → Synthesis of proteins in liver and other tissues

Amino acid synthesis has ______ pathways for different amino acids.

Amino acid synthesis has different pathways for different amino acids.

What does amino acid form when broken down?

Broken down into 2 parts

1. Amino group NH3

• used for synthesis of other a.a.

• forms urea, excreted as waste

• forms other nitrogenous compounds like nitrogenous base of nucleotides

2. Carbon skeleton

• of Glucogenic a.a: enters kreb cycle for ATP synthesis

• of Ketogenic a.a: broken down into acetyl CoA

How are ketone bodies detoxified?

Urea cycle

What happens to amino group during break down of a.a.?

Presence of α-amino group prevents amino acids from oxidative breakdown

Removal of α-amino group involves 3 steps:

1. Transamination

2. Oxidative deamination

3. Urea cycle

Explain Step 1 of removal α-Amino Group: Transamination

Transamination

• For most amino acids, the α-amino (–NH2) group is transferred to α-ketoglutarate.

• amino acid + α-ketoglutarate (via aminotransferase) → glutamate + α-keto acid

• This is a reversible rxn

Write the reaction equation for transamination of aspartate.

C=O and H-C-NH₃⁺ swap places

Write the reaction equation for transamination of alanine

C=O and H-C-NH₃⁺ swap places

What is the enzyme used for transamination?

Amino acid name + aminotransferase e.g. alanine aminotransferase

What are aminotransferases?

• Intracellular liver enzymes

• Substrate specific: Specific only for one amino acid

• Named after amino acid it works on (the amino acid group donor)

e.g. Alanine aminotransferase (ALT), Aspartate aminotransferase (AST)

What keto acids can be formed from transamination and what happens to them after?

The remaining carbon skeleton will eventually be

converted into one of the following seven keto

acids:

• Pyruvate

• Acetyl CoA

• Acetoacetyl CoA

• α-Ketoglutarate

• Succinyl CoA

• Fumarate

• Oxaloacetate

These keto acids are subsequently converted to glucose or ketone bodies

What are the 3 categories of amino acids in terms of breakdown?

After transamination, amino acids formed can be classified as:

1. Glucogenic: converted to glucose

2. Ketogenic: converted to ketone bodies

3. Both glucogenic and ketogenic: converted to either glucose or ketone bodies

What happens to the Keto acid Methionine (Glucogenic)?

Methionine (Glucogenic)

1. Methionine undergoes transamination to form amino group and carbon skeleton

2. Carbon skeleton converted to the keto acid, Succinyl-CoA

3. Succinyl-CoA enters Krebs cycle, is converted to succinate → fumarate → malate → oxaloacetate

4. Oxaloacetate converted to phosphoenolpyruvate

5. Phosphoenolpyruvate converted to glucose

What happens to the Keto acid, Lysine (Ketogenic)?

Lysine (Ketogenic)

1. Lysine undergoes transamination to form amino group and carbon skeleton

2. Carbon skeleton is converted to keto acid, acetyl-CoA

3. acetyl-CoA is converted to ketone body

What happens to the Keto acid, Tyrosine (Both Glucogenic and Ketogenic)?

Tyrosine (Both glucogenic and ketogenic)

1. Tyrosine undergoes transamination to form amino group and carbon skeleton.

Glucogenic pathway:

2a. Carbon skeleton is converted to the keto acid, fumarate → malate → oxaloacetate

3a. Oxaloacetate is converted to phosphoenolpyruvate

4a. Phosphoenolpyruvate is converted to glucose

OR

Ketogenic pathway:

2b. Carbon skeleton is converted to the keto acid, Acetyl-CoA

3b. Acetyl-CoA is converted to ketone body

Explain Step 2 of removal of α-Amino Group: Oxidative deamination

• Glutamate undergoes oxidative deamination to produce ammonia + α-ketoglutarate.

• α-ketoglutarate is then used again for transamination reactions

Write the reaction equation for oxidative deamination

Explain Step 3 of removal of α-Amino Group: Urea cycle.

Draw the structures involved and write out the chemical equation.

• Ammonia enters urea cycle,

• Ammonia is converted to urea. Urea is excreted from the body as urine

Urea cycle

• Requires CO2, aspartate and 3ATP

• Produces urea and fumarate.

• Occurs partly in mitochondrial matrix, partly in cytosol

Draw out the structure of urea and state where each component is from

• Carbonyl group is from CO2.

• One -NH2 group is from ammonia.

• Another -NH2 group is from aspartate.

What is the fate of urea?

• Diffuses from the liver into bloodstream

• Transported in the blood to the kidneys

• In kidneys, filtered and excreted in urine

From what are the 10 non-essential amino acids synthesised from?

From intermediates of glycolysis:

• Serine, Glycine, Alanine

From intermediates of the Krebs cycle:

From Oxaloacetate:

• Asparagine, Aspartate

From α-Ketoglutarate:

• Glutamate, Glutamine, Proline, Arginine

From other (essential) amino acids:

From Phenylalanine:

• Tyrosine

From Methionine:

• Cysteine

Draw the diagram for amino acid degradation (Transamination, Oxidative deamination)

Draw the structure of α-ketoglutarate

Same structure as glutamate, just that H-C-NH₃⁺ is swapped for C=O