Metabolism of Individual Amino Acids Lecture Notes PDF

Metabolism of individual amino Acids  Phenylalanine & tyrosine amino acid metabolism Nature: 1. Aromatic amino acids. 2. Both are mixed glucogenic & ketogenic. 3. Phenylalanine is essential amino acid while Tyrosine is non-essential amino acid....

Metabolism of individual amino Acids  Phenylalanine & tyrosine amino acid metabolism Nature: 1. Aromatic amino acids. 2. Both are mixed glucogenic & ketogenic. 3. Phenylalanine is essential amino acid while Tyrosine is non-essential amino acid. Synthesis of tyrosine: It is synthesized fromphenylalanine in the liver as follow:  Anabolic fates of tyrosine: 1. Synthesis of proteins & phosphoproteins. 2. Catecholamines synthesis: Catecholamines which include: – Adrenaline "epinephrine“: synthesized mainly in adrenal medulla. – Noradrenaline"norepinephrine: synthesized in adrenal medulla, adrenergic nerve endings.  3. Synthesis of melanin: Melanin protects the skin from U.V rays as it ispotent natural antioxidant. It is stored in melanocytes. Synthesized from tyrosine via tyrosinase(tyrosine hydroxylase). 4. Biosynthesis of thyroid hormones: Iodine uptake and concentration by cells of thyroid follicles. Oxidation of iodide ion (I_) into the higher value (I+) by peroxidase. Iodination of tyrosine residue of thyroglobulin atposition 3 & 5 to form mono-iodo-tyrosine (MIT) & di- iodo-tyrosine (DIT). Oxidative coupling of DIT & MIT to form tri-iodo- thyronine"T3" & two molecules of DIT to form tetra- iodo-thyronine " T4“.  Metabolic disorders of phenylalanine 1. Phenylketonuria. 2. Alkaptonuria. 3. Tyrosinosis. 4. Albinism. 1- Phenylketonuria Caused by genetic deficiency of phenylalanine hydroxylase or dihydrobiopterine reductase. This will lead to accumulation of large amounts of phenylalanine in blood & its appearance in urine. An alternative pathway for oxidation of phenylalanine into phenyllactate ,phenylpyruvate& phenylacetate with their accumulation in the blood and their appearance in urine leading to mossy odor of urine  Clinically: 1. Mental retardation: phenylpyruvate in the brain inhibit the transport of pyruvate to the mitochondria from kreb's cycle leading to decreased energy in the brain. 2. Failure to thrive & seizures. 3. Skin lesion "eczema" & light color of hair & skin as Phenylalanine is competitive inhibitor of tyrosinase (key enzyme in melanin synthesis). 4. Mossy odor of urine.  Diagnosis: – Ferric chloride "Fecl3" test must be used as a screening test, to be done 4 days after birth (to allow phenylalanine accumulated in the blood from milk proteins) & before mental retardation develop. –Recently, amino acid profile (aminogram) is used. Treatment by tyrosine rich, phenylalanine low diet till age of 6 years. 2. Albinism: Caused by inherited genetic deficiency of tyrosinase "tyrosine hydroxylase" leading to absence of melanin pigment. Types: 1. Ocular: if this deficiency occurs in the iris only. 2. Cutaneous: if this deficiency occurs in the skin only. 3. Oculocutaneous: if this deficiency occurs in bothskin & iris.  3- Alkaptonuria. Inherited autosomal recessive deficiency of homogentisic acid oxidase. Joints: leading to arthritis with joint pain. Connective tissues: leading to generalized pigmentation (ochronosis). the color of urine is normal when freshly voided but on exposure to air, it turns brownish black due to oxidation of homogentisic acid. Diagnosis by Fehling’s test.