•Residual nitrogen, composition. Utilization of ammonia in the urea cycle and excretion in the urine (reactions,
compartmentation of the urea cycle enzymes, regulation, amount of urea excreted per day in the urine.
Urea is the way most terrestrial vertebrates excrete ammonia.
cycle process
There are five major steps: (1) 1 molecule of ammonia and CO2 are catalyzed by carbamoyl phosphate synthase
to generate carbamoyl phosphate, the reaction is carried out in the mitochondrial matrix, consuming 2 molecules
of ATP; (2) in ornithine ammonia Under the action of formyltransferase, the carbamoyl group of carbamoyl
phosphate is transferred to ornithine to form citrulline, and the reaction is carried out in the mitochondrial matrix;
(3) citrulline is transported from mitochondria to cytoplasm, and arginine succinate Acid synthase catalyzes the
condensation of citrulline and aspartic acid into argininosuccinic acid. The reaction is carried out in the cytoplasm
and consumes two high-energy phosphate bonds in 1 molecule of ATP (to generate AMP); (4) argininosuccinidase
( Lyase) cleaves argininosuccinic acid into arginine, releases fumaric acid, and the reaction is carried out in the
cytoplasm; (5) arginine is hydrolyzed by arginase into urea and ornithine, and ornithine enters the mitochondria,
which can Citrulline is synthesized with carbamoyl phosphate again, and the cycle is repeated.
physiological meaning
(1) The urea cycle not only synthesizes ammonia and CO2 into urea, but also generates a molecule of fumaric acid,
which connects the urea cycle with the citric acid cycle.
(2) The synthesis of urea in the liver is the main way to remove the toxic effect of ammonia, and any problems in
any step of the urea cycle may cause diseases. If a certain enzyme in the urea cycle is completely deficient, the
baby will be comatose or die soon after birth; if it is a partial deficiency, it will cause mental retardation, lethargy
and frequent vomiting. In clinical practice, patients with mild hyperammonemia hereditary diseases are often
relieved by reducing protein intake, because the source of free ammonia is reduced.
(3) The urea cycle also exists in plants, but the transport activity is low, and its significance lies in the synthesis of
arginine. Individual plants can also produce urea, which is decomposed under the action of urease to produce
ammonia, which is used to synthesize other nitrogen-containing compounds, including nucleic acids, hormones,
chloroplasts, heme, amines, alkaloids, etc.
•Genetic defects of urea cycle enzymes, symptoms (hyperammonemia, episodic encepha-lopathies).
The operation of the urea cycle must involve the participation of six enzymes:
① First, in mitochondria, ammonia and C02 form carbamoyl phosphate under the action of carbamoyl
phosphate synthase (CPS) and the allosteric activator N-acetylglutamate;
② Carbamate phosphate is condensed with ornithine to form citrulline under the action of ornithine
carbamoyltransferase (OTC), and then enters the cytoplasm through the mitochondrial membrane;
③In the cytoplasm, citrulline and aspartic acid form arginylsuccinate through the action of arginylsuccinate
synthase (AS);
④ Arginyl succinate is decomposed into arginine and fumarate by arginyl succinate lyase (AL);
⑤ Then, arginase (ARG) decomposes arginine into ornithine and non-toxic urea, the former is converted into
citrulline, and the latter is excreted by the kidneys;
⑥ N-acetylglutamate (NAG) required for the urea cycle is catalyzed by glutamate and acetyl-CoA through
N-acetylglutamate synthase (NAGS). Defects in any of the above enzymes can cause urea cycle disorders and
increased blood ammonia. Except for OTC deficiency which is X-linked dominant inheritance, other enzyme
defects are autosomal recessive inheritance.
The clinical manifestations of various enzyme deficiencies are mainly neurological symptoms caused by
hyperammonemia, but the symptoms vary greatly between different types or between different children of the
same type, and the enzyme deficiency is closer to the urea cycle. At the beginning, the symptoms became more
severe.
Affected infants manifested symptoms after feeding a protein-containing diet, manifested as refusal to eat,
vomiting, shortness of breath, lethargy, and soon entered a deep coma, often with convulsions. There may be a
large liver, increased or decreased muscle tone.
The symptoms of childhood onset are mostly mild, with intermittent attacks. Acute hyperammonemia manifests
as vomiting, neuropsychiatric symptoms such as anxiety, irritability and aggressive behavior, and may appear
drowsiness, coma, anorexia and headache. Chronic hyperammonemia is mainly manifested as progressive
cerebral degeneration symptoms, may have poor physical development and mental retardation.
Hyperammonia encephalopathy refers to hepatic encephalopathy. On the basis of severe liver underlying diseases,
blood ammonia metabolism disorders are caused by incentives, resulting in disorders of the patient's central
nervous system.
•Decarboxylation of amino acids (scheme of reaction, enzymes, coenzymes). Properties of structure of biogenic
amines.
•Formation of biogenic amines: putrescine, spermine, spermidine, cadaverine, γ- aminobu-tyric acid (GABA),
histamine, serotonin, catecholamine. S-adenosylmethionine (SAM) as the primary donor of methyl groups during
biosynthesis of creatine, epinephrine, phospha-tidylcholine and methylation of DNA and propyl groups during
biosynthesis of spermine and spermidine.
•Detoxycation of biogenic amines: oxidative deamination monoamines and diamines, muti-lation. Mono- and
diaminooxidases, scheme of reaction, properties MAO. Inhibitors of MAO.
•Catabolism of phenylalanine and tyrosine. Genetic defects of catabolism of phenylalanine and tyrosine.
•Fate of carbon skeletons of amino acids. Ketogenic and glucogenic amino acids.
•Determination of urea concentration in blood serum.
•Test of phenylpyruvic acid in urine.