Urea cycle

Of the urea cycle (including ornithine and the Krebs-Henseleit cycle) is a biochemical cascade in mammals, the nitrogen-containing decomposition products, especially ammonia, converting into urea, which is then excreted by the kidney. In birds and land-living lizards uric acid is produced and excreted instead. Fish do not require conversion of ammonia in them provides the skin with direct contact to water the easy way of osmosis.

The formation of urea takes place in the kidney in the liver cells (hepatocytes ), and to a lesser extent. The cycle is partially in the mitochondrion, partially located in the cytosol, and therefore transport proteins are required.

Reactions of the urea cycle

Cascade in the mitochondrion

Partial reactions of the CPS -I ( by carbamoyl phosphate synthetase I catalyzes ):

At the end, carbamoyl- phosphate, which is the product inlet into the actual urea cycle in the cytosol. Be catalyzed both steps by the carbamoyl phosphate synthetase I.

Since there is no carrier for the transport of carbamoyl phosphate from the mitochondrion, first a detour via ornithine -citrulline must take place. Both are non-proteinogenic alpha-L- amino acids, they differ exactly by the carbamate group, and they exist for carriers. Carbamoyl phosphate is thus transferred under dephosphorylation on ornithine, citrulline which arises. The reaction is catalyzed by the ornithine transcarbamylase.

Citrulline is transported across the mitochondrial ornithine transporter 1 and 2 in the antiport ornithine in the cytosol.

Cascade in the cytosol

Citrulline is in the cytosol addition of L-aspartate dependent on ATP for argininosuccinate, catalyzed by the enzyme argininosuccinate synthase (ASA).

Argininosuccinate reacts with elimination of fumarate to arginine. Enzyme argininosuccinate lyase is the (ASL ).

In the last step, the enzyme catalyzes arginase 1 ( ARG1 ), the reaction of arginine to ornithine. In this step is formed by consuming H2O isourea, which is in equilibrium with urea.

Aspartatzyklus

The Aspartatzyklus serves the recovery of aspartate from the fumarate. The reactions are similar to those of the citric acid cycle. Fumarate is determined by the cytosolic enzymes, fumarase ' and, malate dehydrogenase ' only to malate and then converted into oxaloacetate. In the oxidation of malate to oxaloacetate produced NADH.

The oxaloacetate transamination with α - amino acid to L- aspartate. As α - amino acid is usually glutamic acid, which is deaminated in the transamination of α -keto acid to α -ketoglutarate. The enzyme catalyzing the, aspartate aminotransferase '. Oxaloacetate can alternatively be introduced also in gluconeogenesis, or go on Transportation anaplerotisch in the citric acid cycle in the mitochondrion.

Energy balance

The overall equation of the urea cycle is:

In the synthesis of a urea molecule are four high-energy compounds cleaved (3 ATP and pyrophosphate ). This corresponds to the energy of 4 ATP molecules.

In the regeneration of the aspartate Aspartatzyklus however, a NADH:

NADH is converted into the respiratory chain in the mitochondria to ATP. A NADH equivalent to 2.5 ATP here.

Medical importance

Congenital defects in the enzymes of the urea cycle lead to an increase in ammonium levels in the blood ( hyperammonemia ). In the urea cycle, an ammonium ion is incorporated into an amino acid, thus removing each step. Therefore, the metabolic disorder is the most difficult when the early steps of the urea cycle, and carbamoyl phosphate synthetase ornithine transcarbamylase affected. Defects later steps of argininosuccinate lyase and arginase, leading to less severe symptoms. The increase of the ammonium level leads to impairment of brain function ( encephalopathy ) to coma. Was treated with exchange transfusion and peritoneal dialysis Before 1979. Since 1979 also phenylacetate and benzoate is given. Phenylacetate and benzoate react with glutamine and glycine to Phenacetylglutamin and N- benzoylglycine ( hippuric acid ), which are excreted in the urine, thus removing nitrogen.