60 - Nitrogen Metabolism and Disposal

Step 1 of Nitrogen Metabolism

Transanimation and Oxidative Deanimation

• results in the removal of the alpha amino group from an Amino Acid

Aminotransferase

• Enzymes responsible for transanimation

• Differenrt enzymes for each AA
  localized in the cytosol and mitochondria

Pyridoxal Phosphate (PLP)

• from vit B6

• coenzyme required for all aminotranferases

Aspartate Aminotransferase (AST)

During AA catabolism, ( ) primarily tranfers Amino groups from glutamate to OAA, forming aspartate, which is used as a source of nitrogren in the urea cycle

This enzyme is an exception to the rule that aminotransferases funnnel amino groups to form glutamate

Hepatic Disease

Plasma AST and ALT are elevated, though ALT is more specific

Glutamate Dehydrogenase

• responsible for oxidative deanimation of glutamate

• Expressed in high levels in liver and kidnet

• in mitochondria

• Uses NAD+ or NADPH depending on whether it is oxidating or reducing

Allosteric Regulators of Glutamate Dehydrogenase

GTP - inhibitor

GDP - activator

NH3

crosses membranes

NH4+

ammonium ion is in aqueous solutions

Roles of Glutamate

1. Disposal of AAs (NH3 from urea cycle)

2. Synthesis of AAs

Histidine

Direct denimation of this forms NH4+ and urocanate

Serine and Theronine

Produce NH4+ from direct deanimation reactions that require PLP

Glutamine and Asparagine

Have R group amides that may be released as NH4+ by Deamidation

Glutaminase reaction

particularly important in the Kidney for pH balance

Purine nucelotide cycle in Muscle and Brain

Allows NH4+ to be released from AAs and leave tissues in the form of glutamine

Transport of Ammonia to the Liver

1. The enzyme glutamine synthetase adds a free NH3 to glutamate to make glutamine in an energy dependent reaction

2. The enzyme alanine aminotranferae (ALT) causes the transanimation of pyruvate in muscle cells, which is reversed in the liver

Step 2 of Nitrogen Metabolism

Production of Urea in the Urea cycle