Lecture 28: Amino Acids as fuel

Question 1

The digestion of proteins involves the hydrolysis of ________ bonds by enzymes called __________. These enzymes work in a sequential manner with each round producing __________ peptides.

Answer 1

Peptide
Proteases
Smaller

Question 2

How do endo- and exopeptidases differ in their hydrolysis of proteins?

Answer 2

Endopeptidases:
- sequential
- each round produces smaller peptides
- Endopeptidases attack (break) peptide bonds within the
protein (peptide) polymer

Exopeptidases:
- Releases amino acids, di- and tripeptides
- Exopeptidases attack (break) the last peptide bond near the end of protein (peptide) polymer

Question 3

In reference to proteases, what is meant by the term ‘zymogen’?

Answer 3

Need to prevent protease activity before reaching the
gastrointestinal tract

Proteases secreted as inactive forms (called zymogens or
proenzymes)

They are then Activated by cleavage of peptides from their structure when appropriate

Question 4

What size peptides can be absorbed from the intestine?

Answer 4

Tri or di peptides via H+ linked Co transporter (HUBS) digested into individual amino acids by cytoplasmic peptidases

Amino acids via Na+ linked transporter (HUBS)

Question 5

The absorption of amino acids cross the luminal membrane of the intestine is like what other molecule?

Answer 5

Uptake into epithelial cells by a transporter similar to the SGLT for glucose:
- Na+ dependent
- Amino acid moving to a higher concentration linked with Na+ moving to a lower concentration

At least six different Na+-dependent carriers (semi-specific): Eg.
- neutral AA
- proline and hydroxyproline
- acidic AA
- basic AA and cysteine

Facilitative transport of amino acids into interstitial fluid then blood

Question 6

What part of the amino acid can be feed into metabolic pathways?

Answer 6

Amino acids as a fuel molecule requires:
- only carbon skeletons
- so must remove nitrogen (Deamination)

Question 7

What is transamination?

Answer 7

Amino acids are deaminated by transferring their amino group to a keto acid - this is Known as a transamination

Catalyzed by aminotransferase enzymes (also called
transaminases)

Question 8

What is an aminotransferase and what is its role?

Answer 8

An aminotransferase (also known as transaminase) is an enzyme that facilitates the transfer of an amino group (–NH₂) from an amino acid to a keto acid - and vice versa.

Question 9

Write the two steps for the general reaction catalyzed by an aminotransferase:

Answer 9

Transamination first step:
Amino group is transferred from the amino acid to the
pyridoxal phosphate (becomes pyridoxamine phosphate)

Transamination second step:
Amino group is transferred pyridoxamine phosphate
(becomes pyridoxal phosphate) to the keto acid

Question 10

What role does the coenzyme pyridoxal phosphate play in an aminotransferase reaction? What vitamin is it derived from?

Answer 10

PLP is a co-enzyme required for transamination reactions

Derived from vitamin B6

Carries:
Amino group (from the amino acid to the keto acid)

Exists in two forms:
- Pyridoxal phosphate (no amino group)
- Pyridoxamine phosphate (with amino group)

Question 11

What is PLP derived from?

Answer 11

Derived from vitamin B6

Question 12

What happens to amino groups when amino acids are being used as a fuel molecule?

Answer 12

NH₄⁺ is toxic to cells, so it must be processed by the following pathway:

Transamination Reaction:
When amino acids are used as fuel, their amino groups (–NH₂) are transferred to keto acids through transamination reactions. For example, the amino group from glutamate can be transferred to pyruvate, forming alanine and regenerating α-ketoglutarate. This prevents the release of free ammonia in tissues.

Transport to the Liver:
Alanine, carrying the amino group, travels in the blood to the liver, where it can safely release the nitrogen.

Release of NH₄⁺:
In the liver, alanine undergoes transamination, transferring its amino group to α-ketoglutarate to regenerate glutamate and convert alanine back to pyruvate. Glutamate then undergoes oxidative deamination (catalyzed by glutamate dehydrogenase), releasing the amino group as NH₄⁺.

Urea Formation:
The NH₄⁺ enters the urea cycle, which converts the toxic ammonia into urea, a non-toxic compound. Urea is then excreted from the body by the kidneys through urine.

Return to α-Ketoglutarate:
After releasing NH₄⁺, glutamate is converted back to α-ketoglutarate through oxidative deamination, allowing it to participate in further metabolic processes, including more transamination reactions or the citric acid cycle.

Question 13

What are the keto acids for the following amino acids? Glutamate, Aspartate and Alanine

Answer 13

Glutamate / a-ketoglutarate

Aspartate / oxaloacetate

Alanine / pyruvate