Transamination and Deamination Reactions

Name the keto acid and its amino acid

a-ketoacid: pyruvate

amino acid: alanine

Name the keto acid and its amino acid

a-ketoacid: oxaloacetate

amino acid: aspartate

Name the keto acid and its amino acid

a-ketoacid: a-Ketoglutarate

amino acid: Glutamate

Describe the process of transamination

-removal of amino group from amino acid which is transferred to a-ketoglutarate > this create an amino acid and a-keto acid

-ENZYME: aminotransferase/PLP B6 derivative

-Amino acid + α-ketoglutarate ⇌ α-keto acid + Glutamate

Describe the structure and significance of PLP

-amine group from amino acid is transferred onto aldehyde carbon of PLP

Describe Alanine Transferase

-converts alanine and a-KG to pyruvate and glutamate

Describe Aspartate transferase

-converts aspatate and a-KG to aspartate and glutamate

Why can’t proline and hydroxyproline undergo transamination?

-They’re secondary amines lack primary amino group needed to go through transamination

-Primary amines are needed to transfer amino groups to pyridoxal

Why can’t lysine and theonine undergo transamination?

They cyclize and become toxic nonmetabolites

Function and location of glutamate dehydrogenase

Regenerates the amino acceptor (a-ketoglutarate) and provides ammonia,

either for reutilization or disposal (urea)

Mitochondrial matrix

Reduced NAD+ to NADH and oxidizes amino acids to a-KG

2 step process: hydrolysis and redox reactions

What is "transdeamination" and how does it work? (Coupling reactions)

The two-step process that funnels amino groups from any amino acid → glutamate → free NH₄⁺, which then feeds into the urea cycle.

Step 1 – Transamination (no net deamination):

• An amino acid transfers its amino group to α-ketoglutarate via aminotransferase + PLP

• α-ketoglutarate → glutamate (gets aminated)

• The original amino acid → its α-keto acid

• This "collects" amino groups from many different amino acids into one form: L-glutamate

Step 2 – Oxidative deamination (net deamination happens here):

• Glutamate dehydrogenase (GDH) acts on glutamate

• Uses NAD⁺ (or NADP⁺) as cofactor

• Products: α-ketoglutarate + NADH (or NADPH) + free NH₄⁺

• This regenerates α-ketoglutarate (so it can accept another amino group) and releases free ammonium

What inhibits the GDH?

High ATP, GTP, NADH > leads to protein synthesis cus your not breaking down proteins

What activates the GDH?

High ADP, GDP, Free Amino Acids > leads to deamination and amino acids breakdown

What is the function of glutaminase

a mitochondrial enzyme that

catalyzes the breakdown of glutamine to form

glutamate.

• Widely distributed in the body.

• Ammonia formed is consumed by the urea

cycle.

What is the function of asparaginase

an enzyme that breaks down

asparagine

How are the TCA cycle and Urea cycle linked?

Connection point: Fumarate

• The urea cycle produces fumarate (from arginino-succinate → arginine)

• This fumarate can enter the TCA cycle (mitochondrial matrix), converting to malate → oxaloacetate (OAA)

Two ways nitrogen enters the urea cycle from TCA intermediates:

1. OAA + glutamate → (via transamination) → aspartate + α-KG

   • Aspartate carries a nitrogen into the urea cycle, combining with citrulline to form argininosuccinate

2. α-KG from the TCA cycle can also pick up ammonia (via GDH, reverse direction) to help regenerate glutamate for more transamination

What is the aspartate-argininosuccinate shunt? (Link between urea cycle & TCA cycle)

• Oxaloacetate (OAA) from the TCA cycle undergoes transamination with glutamate → produces aspartate + α-ketoglutarate

• Aspartate carries a nitrogen (amino group) into the urea cycle

• Aspartate combines with citrulline → forms argininosuccinate

• Argininosuccinate is cleaved (by argininosuccinate lyase) → arginine + fumarate

• Fumarate re-enters the TCA cycle (via fumarase → malate → OAA), completing the loop

Importance of aspartate-argininosuccinate shunt

• This shunt is how a second nitrogen enters the urea cycle (the first comes from free NH₄⁺ combining with CO₂ to form carbamoyl phosphate)

• It directly links the TCA and urea cycles by recycling the same carbon skeleton: OAA → aspartate → fumarate → malate → OAA

• Carbon skeleton = recycled/shared; Nitrogen = donated to urea cycle and lost as urea