We all know “All enzymes are proteins, but not all proteins are enzymes”. Proteins in our body have many significant functions. Apart from the importance of functional proteins called enzymes, it is secondarily used as fuel after carbohydrates and lipids. Note that the proteins are used after the depletion of glucose and fatty acids. Protein is used as an energy source by degradation (catabolism). In short,
Proteins ⇨ Amino acids ⇨ intermediates of glycolysis and Krebs cycle-pyruvate, oxaloacetate, acetyl-CoA, fumarate etc ⇨ enter Krebs cycle and glycolysis ⇨ obtain energy by synthesising ATP
After protein degradation, the amino groups (Ammonia, NH4+) are released, toxic to animals, including humans. In addition, ammonia may cause Cerebral edema (increased water content in the brain), increasing cranial pressure. So ammonia (highly toxic) has to be converted to UREA (less toxic).
Note :
1. In terrestrial organisms, converted to urea – ureotelic
2. In birds and reptiles, converted to uric acid – uricotelic
3. In aquatic organisms, excrete ammonia into the water – ammonotelic
4. In birds, it excretes ammonia only in unusual circumstances.
Urea cycle:
The urea cycle performs to eliminate the toxic ammonia from the body. The amino acid degradation occurs everywhere in muscle cells, and it is carried through the blood to the liver. And the urea cycle occurs in the liver. In hepatocytes (liver cells), mitochondria and cytosol are involved in this cycle. So there are about four significant enzymatic reactions.
The first reaction takes place in mitochondria, and the remaining are in the cytosol. Before the cycle starts, the ammonia is reacted with HCO3- and 2 ATP to form Carbamoyl phosphate in mitochondria.
Reactions:
In Mitochondria:
1. Carbamoyl phosphate reacts with ornithine to form citrulline, catalysed by the enzyme ornithine transcarbamoylase. Citrulline enters the cytosol.
In Cytosol:
2. Citrulline reacts with ATP to form an intermediate, citrullyl AMP, and it is rapidly converted to argininosuccinate by an enzyme called argininosuccinate synthetase.
3. Argininosuccinate is cleaved by the enzyme called argininosuccinase into arginine and fumarate.
4. The free arginine is catalysed by the enzyme arginase to form UREA and Ornithine. Thus urea is formed from ammonia, and the ornithine enters the mitochondria for another cycle.
Did you know?
In an average adult body, 10 to 20 g of ammonia is excreted daily through the urea cycle.
Significance of urea cycle:
1. The highly toxic ammonia is converted into less toxic urea.
2. The synthesis of a semi-essential amino acid called arginine from argininosuccinate.
3. The first member of the reaction, ornithine, which serves as the precursor for proline and polyamines.
4. The rate of the urea cycle in the liver depends on the concentration of N- acetyl glutamate.
Disorders associated with urea cycle:
If the concentration of ammonia increases and accumulates in the liver, it causes hyperammonemia type 1 and type 2 due to the deficiency of the enzymes carbamoyl phosphate synthase and ornithine transcarbamoylase. Citrullinemia and argininemia are disorders due to the accumulation of citrulline and arginine by argininosuccinate synthetase and arginase deficiency.