Metabolism of Nitrogenous Compounds

Metabolism of Nitrogenous Compounds

• The metabolism of nitrogenous compounds is a complex process involving proteins, amino acids, biogenic amines, porphyrins, and nucleobases.
• Learning objectives include describing protein digestion, reactions in separating amino groups, fates of carbon skeletons, glucogenic/ketogenic amino acids, biogenic amines, and examples of nitrogenous compounds.
• Contents of nitrogenous compounds include amino acids (proteins), biogenic amines, porphyrins, and nucleobases.
• Amino acid metabolism involves dietary protein degradation, protein synthesis, and use for energy or creating other compounds. Amino acids can be converted to glucose or fat. Ammonia is produced, and urea is the primary way to remove nitrogen from the body.
• Protein digestion starts in the stomach with the action of proteases, and continues in the small intestine.
• Protein digestion is crucial because large protein molecules cannot be absorbed directly. Enzymes are needed to break peptide bonds, gradually reducing the protein into smaller amino acids.
• Amino acid metabolism aims to separate the amino group (NH3) from the carbon skeleton. Transamination and oxidative deamination are important reactions for this separation.
• The process of separating the amino (NH2) group of an amino acid is vital as it determines the fate of the carbon skeleton.
• The carbon skeleton can be used for energy production through pathways such as the Krebs cycle.
• Glucogenic amino acids can be converted into glucose and ketogenic amino acids can be converted into ketone bodies.
• The urea cycle processes ammonia and converts it into urea, which can be excreted, preventing buildup of toxic ammonia.
• Important considerations in amino acid degradation include transamination (separating amino group), oxidative deamination (removing amino groups converting into ammonia), and metabolism of carbon skeletons.
• Biogenic amines are important neurotransmitters, hormones, and other molecules derived from amino acids.

Amino Acid Degradation

• Transamination transfers amino groups from one amino acid to a keto acid, forming a new amino acid and a new keto acid. This reaction is reversible.
• Oxidative deamination removes amino groups from amino acids, producing ammonia and a keto acid. Oxidative deamination is typically irreversible, generating free ammonia molecules.
• The carbon skeletons of amino acids can enter various metabolic pathways, such as the citric acid cycle (Krebs cycle), to be used for energy production or used to synthesize other substances.
• Different amino acids have different fates, classifying them as glucogenic or ketogenic based on their ability to yield glucose or ketone bodies. The process of these reactions are described in a number of images describing their pathways.

Urea Cycle

• Ammonia, a byproduct of amino acid metabolism, is toxic and needs to be converted to urea for excretion.
• The urea cycle is a series of reactions that takes place primarily in the liver, converting ammonia into urea, which is less toxic and easier to excrete.
• The urea cycle involves multiple enzymes and intermediates, with aspartate and free ammonia from protein degradation playing key roles in producing urea.

Porphyrin Degradation

• Porphyrins are complex nitrogen-containing molecules crucial to various biological processes, notably involved in oxygen transport in hemoglobin.
• Porphyrin degradation disorders are characterized by imbalances in the synthesis or degradation of porphyrins, leading to build-up of toxic intermediates in body fluids like blood and urine, which are then released into the body causing several symptoms.

Nucleotide Metabolism

• Nucleotides are the building blocks of nucleic acids (DNA and RNA).
• Nucleotide metabolism involves the synthesis and degradation of nucleotides.
• Purines and pyrimidines are the building blocks of nitrogenous bases in nucleotides.
• Nucleotide metabolism pathways include the synthesis of purines and pyrimidines from amino acids in the body.
• Synthesis of RNA and DNA involves specific pentose sugars (ribose and deoxyribose), phosphate groups and various nitrogenous bases.

Biogenic Amines

• Biogenic amines are nitrogen-containing aromatic compounds derived from amino acids, acting as neurotransmitters, hormones, and other signaling molecules.
• Tyrosine, tryptophan, histidine, and other important amines are synthesized in the body which play key roles in functions within the body, such as neurotransmission and hormone regulation.
• Biogenic amines derived from different amino acids have diverse roles—such as participating in allergic responses, influencing gastric acid secretion or being important neurotransmitters—