Fumarate pyruvate aspartate
3 moles of ATP are consumed to 1 mole of urea synthesized.
The overall equation of urea synthesis:
CO2 + NH3 + 3 ATP + 2 H2O + Aspartate Urea + 2 ADP + + AMP + Fumarate + 2 Pi + PPi
All enzymes of urea cycle are present only in hepatocytes. Urea is transported in blood to kidney and excreted.
3
.
A certain amount of ammonia is excreted in the urine as ammonium
salts.
The ammonia formation occurs in glutamine. Ammonia accepts a proton
to form ammonium ion. Cell membrane is impermeable for it. Ammonium
ion formation and excretion by kidneys are the mechanism
of proton excretion.
Ammonia excretion in the urine is about 0.5 grams per day in norm. It
increases with acidosis (up to 20 times). In alkalosis excretion of
ammonia is absent.
4. Nitrogen is also excreted in the form of creatinine, which is formed from creatine and creatine phosphate.
5. Some part of ammonia is used for amino acids biosynthesis by reductive amination of -keto acids. This is the main way of amino acids neogenesis in the human body. This reaction is reverse to oxidative deamination of amino acids. Reductive amination of any keto acids is possible. But -ketoglutaric acid and pyruvic acid are aminated the most actively:
Other amino acids are formed by transamination reactions of aspartic and glutamic acids and alanine with the corresponding keto acids. Therefore, alanine, aspartic and glutamic acids are called the primary amino acids, and all others are secondary.
2.4. Violations of nitrogen metabolism
Protein deficiency is a consequence of protein insufficient intake and severe disease when the intake of proteins is enough. It is also developed with monotonous nutrition of plant origin proteins. Negative nitrogen balance, hypoproteinemia, a violation of the water and electrolytes balance are its characteristic features. The disease kwashiorkor is prevalent among children in developing countries. It occurs in severe nutritional dystrophy. Severe liver damage, cessation of growth, a sharp decrease in resistance to infection, edema, atonia of the muscles are experienced. The disease often results in death.
Hyperammonemia is the elevated level of ammonia in the blood.
Causes of hyperammonemia are genetic defects of urea cycle enzymes in the liver. There are five hereditary diseases caused by deficiency of five enzymes of urea cycle. It leads to accumulation of the substrate of the enzyme and its precursors in blood.
For example, the deficiency of the first enzyme carbamoyl phosphate synthetase I. leads to the accumulation of ammonia and its precursors amino acids, mainly glutamine and alanine. The concentration of ammonia may exceed the normal concentration in 10-20 times, of glutamine in 2-3 times.
Hyperammonemia may be acquired and is often observed in cirrhosis and other liver diseases.
Hyperammonemia is accompanied by the following symptoms: nausea, repeated vomiting, dizziness, convulsions, fainting, swelling of the brain (in severe cases), mental retardation (in chronic congenital form).
Accurate diagnosis of the hyperammonemia type can be set by determining the ornithine cycle metabolites in blood or urine, as well as by measuring of enzyme activity in the liver biopsy.
Treatment of patients with various defects in urea cycle is mainly aimed at reducing the ammonia concentration in the blood due to low protein diet, the introduction of keto acids in the diet and stimulation of ammonia excretion to bypass the broken reaction.
Hyperaminoaciduria may be renal associated with defects in amino acid reabsorption in the kidney and extra renal due to an increase in the concentration of amino acids in the blood.
Hereditary defects of amino acids absorption in the kidney are more common. For example, cystinosis is associated with congenital disorders of reabsorption of almost all amino acids in the renal tubule. There is an increase in the excretion of amino acids in 5-10 times, cystine and cysteine in 20-30 times. Selective deposition of cystine in the reticular cells of the bone marrow, spleen, liver and cornea cells is observed.