Carbamoyl phosphate.
When amino acids are used for energy, their carbon skeletons are transformed by a variety of pathways into acetyl CoA or intermediates of glycolysis or the citric acid cycle. While the degradative pathways of some amino acids are complex and beyond the scope of the MCAT, the simpler transaminase pathways are within the scope of study. It is very good to have a general sense of this subject even though you don't need to memorize all six steps in the breakdown of leucine.
One very important topic is the fate of α-amine group when the breakdown of an amino acid occurs. As a general rule these amine groups will be converted into urea and then excreted. The pathway by which this occurs is called the urea cycle. The urea cycle takes place primarily in the liver, and to a lesser extent in the kidney. It was the first metabolic cycle discovered (Hans Krebs and Kurt Henseleit, 1932), five years before the discovery of the citric acid cycle.
Conceptual Vocabulary for Urea Cycle
Urea Cycle
Amination is the process by which an amine group is introduced into an organic molecule.
Urea, also known as carbamide, is an organic compound with chemical formula CO(NH2)2. This amide has two –NH2 groups joined by a carbonyl (C=O) functional group.
Transamination (or aminotransfer) is the reaction between an amino acid and an alpha-keto acid in which the amino group is transferred from the former to the latter.
The urea cycle (also known as the ornithine cycle) is a cycle of biochemical reactions occurring in many animals that converts ammonia into a less toxic substance.
As an intermediary metabolite in nitrogen disposal through the urea cycle, carbamoyl phosphate is produced from bicarbonate, ammonia (derived from amino acids), and phosphate (from ATP).
Citrulline is made from ornithine and carbamoyl phosphate in one of the central reactions in the urea cycle.
Arginosuccinate is synthesized from citrulline and aspartate in the urea cycle.
Carbamoyl phosphate synthetase I transfers an ammonia molecule from glutamine or glutamate to a molecule of bicarbonate that has been phosphorylated by a molecule of ATP. The resulting carbamate is then phosphorylated with another molecule of ATP.
A transaminase or an aminotransferase is an enzyme that catalyzes the transfer of an amine group between an amino acid and an alpha-keto acid.
Ornithine transcarbamylase catalyzes the reaction between carbamoyl phosphate and ornithine to form citrulline and phosphate.
Argininosuccinate lyase catalyzes the reversible breakdown of argininosuccinate producing the amino acid arginine and dicarboxylic acid fumarate.
Arginase catalyzes the hydrolysis of arginine to form ornithine and urea. It is the final enzyme of the urea cycle.
In vertebrae and mammals, N-acetylglutamate is the allosteric activator molecule to mitochondrial carbamyl phosphate synthetase I (CPSI) which is the first enzyme in the urea cycle.
Pyridoxal-phosphate (vitamin B6) is a coenzyme in all transamination reactions, and in some decarboxylation and deamination reactions of amino acids.
