406: Detox, Amino Acid Synthesis, and Cofactors

Alanine Degradation

Generates Pyruvate via alanine transaminase

Glutamine degradation

Generates glutamate + NH3 via glutaminase

Non-skeletal muscle

Glutamate degradation

Generate a-KG + NH3 via glutamate dehydrogenase

Alanine Transaminase Reactants and Products

Alanine + a-KG ←→ Pyruvate + Glutamate

Glutamate dehydrogenase regenerates a-KG, NADH (energy), and NH3

Detoxification of Ammonia in Non-muscle Tissue

Glutamate in non-muscle is converted to glutamine to be transported to liver, then back to glutamate → a-KG and aspartate → aspartate for urea synthesis with NH3

Detoxification of Ammonia in Muscle Tissue

CAHILL CYCLE: glucose between liver and muscle tissue

Transaminase reactions in muscle → Alanine to liver → Pyruvate + Glutamate → NH3 via glutamate DH → Carbamoyl phosphate → Urea

What is required for urea synthesis in non-muscle?

Aspartate

Cahill Cycle

Cycle of Glucose, pyruvate, and alanine between liver and skeletal muscle 

Detox of Ammonia in muscle tissue requires…

PYRUVATE (due to alanine)

First step of urea cycle is in…

The mitochondria of the liver

Remaining is in the cytoplasm

NH3 enters urea cycle as….

Aspartate and carbamoyl phosphate

Aspartate = organic A.A.

Carbamoyl phosphate = inorganic

Energy requirement to make Urea:

4 high energy phosphate bond (3 ATP, 1 PPi)

We can build these amino acids:

Alanine, Glutamine, and Glutamate because they are important to detoxifying nitrogen (as ammonia)

Apart from detox, glutamine is important for…

Nucleotide synthesis

Apart from detox, glutamate is important for…

Precursor to biologically important molecules (like folate/nucleotides)

Coenzymes of Nitrogen metabolism

• Pyridoxal phosphate (B6) - alanine transaminase

• Folic acid (B9) - one-carbon metabolism

• B12 - one carbon metabolism

B12 Function

Methyltransferase reaction (donates methyl to homocysteine to detoxify it)

Tetrahydrofolate (B9 Derivative)

Carries a methyl group on N5 for carbon metabolism and biosynthesis of purine and thymine

MAJOR methyl donor of 1-C metabolism

S-adenosylmethionine (AdoMet)

S-adenosylmethionine (AdoMet)

Major methyl donor containing adenosine from ATP and methionine

Amino acids are precursors to…

Methyl groups

The FIRST methyl group comes from…

Serine

Path of methyl group in 1-C Metabolism

Serine → THF (B9) → B12 → Homocysteine → S-AdoMet → Substrate