UREA
The purpose of the urea cycle (aka ornithine cycle) is to get rid of excess nitrogen by converting ammonia to urea.
The urea cycle consists of five reactions - two mitochondrial and three cytosolic. The cycle converts two amino groups, one from NH4+ and one from Asp, and a carbon atom from HCO3-, to urea. Urea is relatively nontoxic. Ammonia is quite neurotoxic. One urea cycle, producing one urea molecule, costs of four "high-energy" phosphate bonds (3 ATP hydrolyzed to 2 ADP and one AMP).
Orn is the carrier of these carbon and nitrogen atoms. Ornithine is one of the products of the action of the enzyme arginase on L-arginine, creating urea. Therefore, ornithine is a central part of the urea cycle, which allows for the disposal of excess nitrogen. Ornithine is not an amino acid coded for by DNA, and, in that sense, is not involved in protein synthesis. However, in mammalian non-hepatic tissues, the main use of the urea cycle is in arginine biosynthesis, so as an intermediate in metabolic processes, ornithine is quite important.
What are the sources of the nitrogens and carbons in urea? One nitrogen each from aspartate and ammonia. The carbon comes from bicarbonate.
How many high-energy bonds are required to form urea? 4: three ATP's and one AMP.
What is the rate-limiting enzyme in the urea cycle and the metabolites that regulate it? CPS1, aka carbamoylphosphate synthetase, makes carbamoyl phosphate from CO2 and NH3, eats two ATP, needs N-acetylglutamate as an allosteric activator.
What is N-acetylglutamate? Oh, that's what we're just calling glutamate. Glutamate is formed from the breakdown of amino acids, and is split in half into ammonia and apsartate. The asparatate goes into the cycle, fumarate goes out (to the Krebs cycle) and arginine is produced, which either goes on to be excreted as urea, or gets used again. Apparently we don't always make enough arginine to get by, so it's considered an essential amino acid.
Summarize the overall plan of amino group metabolism. Amino acids are broken down to glutamate, in a reaction that also converts alphaKG to an alpha keto acid (removes an amino group and leaves a ketone). Those keto acids just sit around until there's more of them than of alphaKG, and then the reaction as readily goes in the other direction.
Which types of defects provide the greatest accumulation of ammonia in the blood? Defects in any of the urea cycle enzymes causes hyperammonemia.
Why is hyperammonemia a problem? Because ammonia is a neurotoxin. The exact mechanisms of its toxicity are not clear to me.
Ammonia is a compound with the formula NH3. It is normally encountered as a gas with a characteristic pungent odor. Ammonia contributes significantly to the nutritional needs of terrestrial organisms by serving as a precursor to foodstuffs and fertilizers. Ammonia, either directly or indirectly, also is a building block for the synthesis of many pharmaceuticals. Although in wide use, ammonia is both caustic and hazardous.
Ammonia, as used commercially, is often called anhydrous ammonia. This term emphasizes the absence of water in the material. Because NH3 boils at -33 °C, the liquid must be stored under high pressure or at low temperature. Its heat of vaporization is, however, sufficiently great that NH3 can be readily handled in ordinary beakers in a fume hood. "Household ammonia" or "ammonium hydroxide" is a solution of NH3 in water. The strength of such solutions is measured in units of baume (density), with 26 degrees baume (about 30 weight percent ammonia at 15.5 °C) being the typical high concentration commercial product. Household ammonia ranges in concentration from 5 to 10 weight percent ammonia.
The carboxylate anion of glutamic acid is known as glutamate, and this is one of the 20 proteinogenic amino acids. It is not among the human essential amino acids. Its codons are GAA and GAG. As its name indicates, glutamic acid has a carboxylic acid component to its side chain. At pH7, the amino group is protonated and one or both of the carboxylic groups will be ionized. Hence, the species has a charge of -1, and is referred to as glutamate. The pKa value for glutamic acid is 4.1, which means that below this pH, the carboxylic acid groups are not ionized in more than half of the molecules.