Reactions of the carboxyl group

1. Decarboxylation of amino acids. Prosthetic group of L-amino acid decarboxylases is pyridoxal phosphate (the active form of vitamin B₁). Amines are products of amino acids decarboxylation. Since they are formed as the metabolic products and possess high physiological activity they are called biogenic amines.

4 types of amino acid decarboxylation were founded. α-Decarboxylation is characteristic for animal tissues.

Decarboxylation of histidine leads to histamine formation. It causes vasodilatation in inflammation, is involved in the secretion of hydrochloric acid in the stomach, which is used in the clinic in the study of gastric secretory activity (histamine test). With high sensitivity to histamine antihistamines are used.

Decarboxylation of glutamic acid leads to -aminobutyric acid (GABA) formation:

НООСCH(NH₂)CH₂CH₂COOH NH₂CH₂CH₂CH₂COOH + СО₂

glutamic acid  aminobutyric acid

It accumulates in the brain tissue and is the neurohumoral inhibitor. GABA is used in the clinic as a medicine for certain diseases of the CNS.

Decarboxylase of aromatic amino acids catalyzes decarboxylation of 3,4-dihydroxyphenylalanine (DOPA). Dopamine is produced. It is a precursor of adrenaline (epinephrine) and noradrenaline (norepinephrine).

The accumulation of biogenic amines can cause violations of some functions in the body. There are special mechanisms of neutralization of biogenic amines. There is their oxidative deamination with the formation of aldehydes and ammonia. Enzymes are monoamine oxidases and di-amine oxidases. The process is irreversible and proceeds in two stages:

Hydrogen peroxide then splits into water and oxygen. Monoamine oxidase (MAO), FAD-containing enzyme, is localized primarily in the mitochondria.

2. Aminoacyladenylate formation.

This reaction of the amino acid with ATP is catalyzed by enzymes of ligases class. In the form of aminoacyladenylate amino acids are transported by the tRNA.

The carbon skeletons of amino acids can be included into the TCA cycle. Most of the amino acids are called glycogenic. They serve as a source of carbohydrates in the body. Gluconeogenesis is enhanced in diabetes, with adrenal cortex hyperfunction and the introduction of glucocorticoids.

Two amino acids (leucine and lysine) are considered ketogenic because they are the precursors of ketone bodies. Four amino acids (isoleucine, phenylalanine, tyrosine, tryptophan) are glycogenic and ketogenic.

2.3. Ammonia neutralization in the body

The main source of ammonia in the body is the deamination of amino acids and nucleotides. About 70 g of amino acids are broken down per day. Ammonia is highly toxic. Elevation of ammonia concentration in the blood is harmful to the brain. The level of ammonia in the blood does not exceed 60 mcmol/l in norm. It has been shown in experiments on rabbits that the concentration of ammonia 3 mmol/l is lethal.

Storage and transport of ammonia

1. Aspartic and glutamic provide immediate binding of NH₃ when it is formed in cells. Enzymes asparagine synthetase and glutamine synthetase belong to ligases class. ATP using is necessary.

The synthesis of glutamine is particularly active in muscle, brain and liver. Some part of ammonia binds to -ketoglutaric acid.

Ammonia is removed from the brain predominantly as glutamine. Glutamine and asparagine are excreted in the urine in small quantities. Their function is storage and transport of ammonia in a nontoxic form. Alanine also performs transport function.

Amidation of aspartic and glutamic acids can also occur in the case when they are part of the protein molecule. This provides an immediate binding of ammonia wherever it occurs as a result of metabolism.

2. Urea is the main end product of protein metabolism in many animals. Urea nitrogen is about 90% of the total output of nitrogen. Urea is synthesized in liver. This process includes several stages, which form urea cycle (ornitine, or Krebs – Henselein cycle).

1. Formation of carbamoyl phosphate from NH₃, CO₂ and ATP is done under the action of carbamoyl phosphate synthetase. Carbamoyl phosphate is the energy rich compound. It is metabolically active form of ammonia:

NH₃+ CO₂ + 2 АТP + Н₂ОH₂NСООРО₃Н₂ + 2АDP + Н₃РО₄

In humans, two ways of carbamoyl phosphate synthesis have been discovered:

a) the reaction which is catalyzed by the enzyme ammonia dependent carbamoyl phosphate synthetase. It was opened in mitochondria of liver cells and is primarily used for the synthesis of arginine and urea;

b) the reaction which is catalyzed by glutamine dependent carbamoyl phosphate synthetase. The donor of amino group is glutamine. It was opened in the cytosol and primarily is used for the synthesis of pyrimidine nucleotides.

2. The condensation of ornithine and carbamoyl phosphate. The enzyme is ornithine transcarbamoilase. Citrulline is formed. The 1st and 2nd reactions occur in mitochondria.

3. Citrulline passes into the cytosol and reacts with aspartic acid. Argininosuccinate is formed. The enzyme is argininosuccinate synthase.

4. Argininosuccinate cleaves to give arginine and fumarate. The enzyme is argininosuccinase. Fumarate provides a connecting link with Krebs cycle, gluconeogenesis and other processes.

5. Hydrolysis of arginine and urea formation. The enzyme is arginase.

One nitrogen atom in urea is from ammonia and the second is from aspartate.

The resulting ornithine is involved in the urea cycle. Fumarate is converted to aspartate: