Amino Acid Metabolism

• dietary intake

• Proteolysis

• Degradation of select molecules

• De novo synthesis within the body

The sources of amino acids within the body

They are catabolized as AA’s are not stored within the body. Excess AA’s are only used for protein synthesis when protein is needed

What happens to excess AA’s in the body

• N theme: where ammonia contained in AA’s is turned to non toxic urea for excretion

• C theme: where the AA’s carbon skeleton enters the kerbs cycle and combined gluconeogenesis to form glucose

The two breakdown pathways of AA’s and what they are fed by

Both N and C themes within the liver

Where does AA metabolism occur

1. Removal of primary amino group from AA (deamination)

2. Synthesis of a alpha-keto acid

3. Detoxification of ammonia

The steps of AA metabolism N theme

Glutamate dehydrogenase

Enzyme used in step 1, deamination of AA in N theme

Catalyze the reversible reaction of switching R groups between a amino acid and alpha-keto acid forming a new amino acid and alpha-keto acid

The function of transaminases

alpha-ketoglutarate with AA 1 to then from keto acid 1 and glutamate

Almost all transaminases use the amino acid and keto acid

Pyridoxal phosphate which is Vit B6 (pyridoxine) with a phosphate group

Transaminases require prosthetic groups

The glutamate-aspartate transporter as it shuttles AA’s between the inter membrane space and matrix to allow conversion between aspartate and glutamate with the use of keto acids oxaloacetate and alpha-ketoglutarate from the coupled malate-alpha-ketoglutarate transporter

The section of the malate-aspartate shuttle that has transaminase activity

Aspartate aminotransferase

The glutamate-aspartate transporter uses enzyme that is a transaminase

ALT and AST

The two transaminases that are clinical measures of liver damage

They are in equal levels in 1:1 ratio

AST and ALT in the liver are equimolar meaning

They are released into the blood, but AST is released twice as fast

Usually AST and ALT are in the blood at low levels but during liver damage

Liver damage by alcohol, cancer or hepatitis infections

If blood AST:ALT ratio is >2 this is caused by

Non liver sources

If blood AST:ALT ratio is > 5 this is caused by

• serine dehydratase and threonine dehydratase

• Pyridoxal phosphate

Serine and threonine are deaminated by enzymes … which require …