Amino acids metabolism: disposal of Nitrogen

• ▪ Glutamine is converted to glutamate by glutamate synthase, which is then converted to α - ketoglutarate.
• Catabolism of the amino acids involves the removal of α-amino groups, followed by the breakdown of the resulting carbon skeletons.
• Pathways converge to form 7 intermediate products: oxaloacetate, pyruvate, α-ketoglutarate, fumarate, succinyl-CoA, acetyl-CoA, and acetoacetate.
• E, and histidine are types of amino acids.
• Glutamine is converted to glutamate and ammonia by the enzyme glutaminase.
• Glutamate is converted to α-ketoglutarate by either transamination by aminotransferase or through oxidative deamination by glutamate dehydrogenase.
• Proline is oxidized to glutamate; glutamate is transaminated or oxidatively deaminated to form α-ketoglutarate.
• Arginine is cleaved by arginase to produce ornithine.
• These products directly enter the pathways of intermediary metabolism, resulting either in the synthesis of glucose (gluconeogenesis), the synthesis of lipid, or the production of energy through their oxidation to CO2 by the citric acid cycle.
• Nutritionally nonessential amino acids can be synthesized in sufficient amounts from the intermediates of metabolism or, as in the case of cysteine and tyrosine, from nutritionally essential amino acids.
• Alkaptonuria (Alcaptonuria) is a rare metabolic condition involving a deficiency in homogentisic acid oxidase, resulting in accumulation of homogentisic acid.
• The reaction of Alkaptonuria occurs in the degradative pathway of tyrosine.
• The three characteristic signs and symptoms of Alkaptonuria are: Homogentisic aciduria, large joint arthritis, and black ochronotic pigmentation of cartilage and collagenous tissue.
• Patients with Alkaptonuria are usually asymptomatic until about age 40.
• Dark staining of the diapers can indicate the disease in infants, but usually no symptoms are present until later in life.
• Diets low in protein, especially in Phe and Tyr, help reduce levels of homogentisic acid and decrease pigment deposition (ochronosis) in body tissues.
• Although Alkaptonuria is not life-threatening, the associated arthritis may be severely crippling.
• In contrast, the nutritionally essential amino acids cannot be synthesized (or produced in sufficient amounts) by the body and, therefore, must be obtained from the diet in order for normal protein synthesis to occur.
• Genetic defects in the pathways of amino acid metabolism can cause serious disease.
• Single carbon groups such as ylene and methyl groups can be transferred from carrier compounds like tetrahydrofolate (THF) and S-adenosylmethionine (SAM) to specific structures that are being synthesized or modified.
• The "one-carbon pool" refers to single carbon units attached to this group of carriers.
• Carbon dioxide (CO2), the dehydrated form of carbonic acid, is carried by the vitamin biotin, which is a prosthetic group for most carboxylation reactions.
• Biotin is not considered a member of the one-carbon pool.
• Defects in the ability to add or remove biotin from carboxylases result in multiple carboxylase deficiency.
• Treatment for multiple carboxylase deficiency is supplementation with biotin.
• The active form of folic acid is tetrahydrofolic acid or tetrahydrofolate (THF).
• THF is produced from folate by dihydrofolate reductase in a two-step reaction requiring two NADPH.
• The carbon unit carried by THF is bound to nitrogen N5 or N10, or to both N5 and N10.
• THF allows one-carbon compounds to be recognized and manipulated by biosynthetic enzymes.
• Threonine is categorized as glucogenic, however, it must be emphasized that threonine is both ketogenic and glucogenic.
• Amino acids whose catabolism yields pyruvate or one of the intermediates of the citric acid cycle are termed glucogenic.
• These intermediates are substrates for gluconeogenesis.
• Carbon skeletons of glucogenic amino acids can give rise to the net formation of glucose in gluconeogenic organs (liver and kidneys).
• Amino acids whose catabolism yields either acetoacetate or one of its precursors (acetyl CoA or acetoacetyl CoA) are termed ketogenic.
• Acetoacetate is one of the ketone bodies, which also include 3-hydroxybutyrate and acetone.
• Leucine and lysine are the only pure ketogenic amino acids found in proteins.
• Their carbon skeletons are not substrates for gluconeogenesis and, therefore, cannot give rise to the net formation of glucose.
• The reaction requires molecular oxygen and the coenzyme tetrahydrobiopterin.
• Amino acid metabolism involves the degradation and synthesis of amino acids.
• Tyrosine, like cysteine, is formed from a nutritionally essential amino acid.