Protein metabolism II v Metabolism of Aromatic amino

Protein metabolism II v. Metabolism of Aromatic amino acids v. Metabolism of Sulphur containing amino acids

Metabolism of aromatic amino acids

Aromatic amino acids v. Phenylalanine v. Tyrosine v. Tryptophan

Structure Phenylalanine CH 2 CH NH 2 COOH

Synthesis Essential amino acid - not synthesized in the body and has to be provided through the diet.

Structure Phenylalanine CH 2 CH COOH NH 2 Tyrosine HO CH 2 CH NH 2 COOH

Synthesis Non essential amino acid- synthesized in the body from phenylalanine

Synthesis O 2 Phenylalanine H 2 O Tyrosine Phenylalanine hydroxylase Dihydrobiopterin Tetrahydrobiopterin Dihydrobiopterin reductase NADP + NADPH+H +

Functions 1. Constituent of proteins: required for the protein synthesis

Functions 2. Synthesis of biologically important compounds §Catecholamines §Thyroid hormones § Melanin

Functions 2. Synthesis of biologically important compounds §Catecholamine's Epinephrine Norepinephrine Dopamine

Functions a) Synthesis of catecholamine's Site: In adrenal medulla & sympathetic ganglia Function: § Increase blood pressure §Increase contraction and rate of heart §Stimulates glycogenolysis and lipolysis §Dopamine is a inhibitor of prolactin secretion §Dopamine is a neurotransmitter in extrapyramidal tract, substantia nigra

Functions b) Synthesis of thyroid hormones Site: In thyroid gland under the influence of TSH Functions §Increases basal metabolic rate (BMR) §Increases heart rate and force of contraction of heart muscle §Increases protein sythesis §Activates gluconeogenesis and glycogenolysis

Melanin

Functions c) Synthesis of melanin Function : gives black colour to skin hair and eyes. Protects the skin against harmful ultraviolet rays

Summary Phenyl alanine Thyroid Hormones Tyrosine (T 3 & T 4) Glucos Fat Proteins e Catecholamine's (Epinephrine, Norepinephrine, Dopamine)

Inborn errors of phenylalanine and tyrosine metabolism 1. Phenyl ketonuria (PKU) 2. Alkaptonuria 3. Albinism

Inborn errors of phenylalanine and tyrosine metabolism 1. Phenyl ketonuria (PKU) Autosomal recessive disorder Incidence: 1 in 10, 000 births

Inborn errors of phenylalanine and tyrosine metabolism 1. Phenyl ketonuria (PKU) Biochemical defect Phenyalanine hydroxylase Phenylalanine Transamination Phenylpyruvate Reduction Decarboxylation Phenyllactate Phenylacetate Conjugation (Glutamine) Phenylacetyl glutamine Tyrosine

Inborn errors of phenylalanine and tyrosine metabolism 1. Phenyl ketonuria (PKU) Clinical features CNS §Mental retardation §Seizures §Tremors §Hyperactivity §Delayed milestones

Inborn errors of phenylalanine and tyrosine metabolism 1. Phenyl ketonuria (PKU) Clinical features §Hypo pigmentation of skin and hair §Mousy body odour

Inborn errors of phenylalanine and tyrosine metabolism 1. Phenyl ketonuria (PKU) Diagnosis §Serum phenylalanine estimation

Inborn errors of phenylalanine and tyrosine metabolism 1. Phenyl ketonuria (PKU) Treatment §Early detection is important since mental retardation is preventable if detected at the earliest. (About 5 units of IQ lost for each 10 week delay in starting treatment) §Provide a special diet containing low phenylalanine (Tapioca based food has low phenylalanine) Special diet to be continued for the first decade of life , after which the child can have normal food

Inborn errors of phenylalanine and tyrosine metabolism 2. Alkaptonuria Autosomal recessive disorder Incidence: 1 in 250, 000 births

A 1 -year old girl presents with delayed mile stones, mousy odor , hypopigmentation. 1. Identify the inborn error of metabolism 2. What is the biochemical defect ?

Inborn errors of phenylalanine and tyrosine metabolism 2. Alkaptonuria Biochemical defect Homogentesic acid oxidase Homogentisic acid Maleyl aceto acetic acid Oxidation Urine & Polymerisation Alkaptone bodies (black pigment) Deposition in connective tissues (Bones, cartilage of nose, pinna of ear) (Ochronosis) Arthritis

Inborn errors of phenylalanine and tyrosine metabolism 2. Alkaptonuria Clinical features

Inborn errors of phenylalanine and tyrosine metabolism 2. Alkaptonuria Diagnosis Urine §Ferric chloride test +ve §Benedicts test+ve

Inborn errors of phenylalanine and tyrosine metabolism 2. Alkaptonuria Treatment Alkaptonuria is not a dangerous condition. So no specific treatment is required. However consumption of protein diet with relatively low phenylalanine content is recommended.

Inborn errors of phenylalanine and tyrosine metabolism 3. Albinism Autosomal recessive disorder Incidence: 1 in 20, 000 births

Inborn errors of phenylalanine and tyrosine metabolism 3. Albinism Biochemical defect Tyrosinase Tyrosine Melanin

Inborn errors of phenylalanine and tyrosine metabolism 3. Albinism Clinical features §Hypopigmentation of the skin, hair and eyes §Increased sensitivity to sunlight. Increased susceptibility to skin cancer §Photophobia (Intolerance to light)

Inborn errors of phenylalanine and tyrosine metabolism 3. Albinism Treatment Not specific Avoid exposure to UV rays

Structure CH 2 CH COOH Tryptophan N H NH 2

Synthesis Essential amino acid - not synthesized in the body and supplied through diet

Functions 1. Constituent of proteins: required for the protein synthesis

Functions 2. Synthesis of biologically important compounds a) Serotonin

Functions a) Synthesis of serotonin Site: mast cells, platelets and gastrointestinal tract mucosa Functions: a)Brain- neurotransmitter, stimulates cerebral activity (excitation). Serotonin is involved in regulation of behavioral patterns, sleep, appetite and temperature b)Stimulator of smooth muscle contraction Vasoconstrictor GIT - increases motility of GIT Bronchoconstriction

Functions b) Synthesis of melatonin Site: pineal gland in brain. Function: a) Melatonin involved in diurnal variations of the body, sleep wake cycles and the biological rhythms. b) Melatonin blocks the production of melanocyte stimulating hormone(MSH) and adrenocorticotropic hormone (ACTH)

Functions c) Synthesis of niacin About 3% of tryptophan molecules are diverted at the level of 3 - hydroxy anthranilate to form NAD. About 60 mg of tryptophan will be equivalent to 1 mg of niacin

Summary Diet Tryptophan Proteins Glucose Fat Coenzyme of niacin(NAD) Serotonin Melatonin 5 hydroxy indole acetic acid

Inborn errors of tryptophan metabolism 1. Hartnup’s disease Autosomal recessive disorder

Inborn errors of tryptophan metabolism 1. Hartnup’s disease Biochemical defect Defect in transport of tryptophan and other neutral amino acids from the intestine, renal tubules and brain

Inborn errors of tryptophan metabolism 1. Hartnup’s disease Clinical features §Dermatitis-due to decreased niacin §Cerebral ataxia due to decreased serotonin §Mental retardation

Inborn errors of tryptophan metabolism 1. Hartnup’s disease Treatment High protein diet Niacin supplementation

Metabolism of sulphur containing amino acids

sulphur containing amino acids Methionine Cysteine Cystine

Structure Methionine Met (M) CH 2 S CH 3 CH 2 CH NH 2 COOH

Synthesis Essential amino acid - not synthesized in the body and has to be provided through the diet.

Catabolism Synthesis of S-adenosylmethionine (SAM)

Catabolism 1. Synthesis of S-adenosylmethionine (SAM / active methionine) CH 2 S CH 3 CH COOH NH 2 ATP Methionine CH 2 S CH 3 Adenosine CH Methionine COOH NH 2 SAM PPi +Pi Methionine H 2 O adenosyl transferase S-adenosylmethionine (SAM or active methionine)

Functions 1. Constituent of proteins Methionine is the first amino acid to be incorporated during protein biosynthesis, either as methionine (in eukaryotes) or formyl methionine (in prokaryotes)

Functions 2. S-adenosylmethionine: Principal donor of methyl group in transmethylation reactions in the body Active methyl group (Labile) CH 2 +S CH 3 Adenosine CH COOH NH 2 SAM S-adenosylmethionine (SAM or active methionine)

Functions Transmethylation reaction S-adenosylmethionine (SAM or active methionine) Acceptor Methyl transferase Methylated acceptor S-adenosyl homocysteine (SAH)

Examples of transmethylation reaction S-adenosylmethionine (SAM) Nor epinephrine Methyl transferase Epinephrine S-adenosyl homocysteine (SAH)

Examples of transmethylation reactions Methyl Acceptor Methylated product Norepinephrine Epinephrine Guanido acetic acid Creatine Ethanolamine Acetyl serotonin Choline Melatonin

Significance of transmethylation reaction §Synthesis of biologically important compounds Egs: Epinephrine, creatine, choline, melatonin §SAM also serves as precursor for the synthesis of polyamines

Summary Proteins Diet Methionine SAM Glucose Cysteine Transmethylation