The Objectives [lecture 4]
Inborn Errors of 1. Phenylketonuria (PKU) Amino Acid 2. Maple Syrup Urine Disease (MSUD) Metabolism 3. Albinism 4. Homocyteinuria 5. Alkaptonuria
Red = Green = Blue = Import- addition explain ant notes
Med432 Biochemistry Team / Done By : Rehab Mosleh ,Ethar Alqarni and Haifa Aldabjan Reviewed by : Abdullah alatawi , Saleh alneghamishi
Med432 Biochemistry Team
Inborn Errors of Amino Acid Metabolism
Maple Syrup Urine Phenylketonuria Disease Albinism Homocyteinuria Alkaptonuria
Classical phenylalanine Deficiency of branched chain Cystathionine β-synthase Tyrosinase deficiency hydroxylase deficiency α-ketoacid dehydrogenase deficiency Homogentisic acid oxidase
Atypical Tetrahydrobiopterin deficiency Med432 Biochemistry Team
Inborn Errors of Amino Acid Metabolism Caused by enzyme loss or deficiency due to gene loss or gene mutation Normal amino acid metabolism Cofactors Enzyme + Substrate Product
But if there are any deficiency of either enzyme or cofactor There will be abnormality of amino acid metabolism
There are five examples for these abnormality: 1. Phenylketonuria (PKU) 2. Maple Syrup Urine Disease (MSUD) 3. Albinism 4. Homocyteinuria 5. Alkaptonuria Amino acid phenylalanine Med432 Biochemistry Team involved Phenylketonuria (PKU)
types
Cause Due to deficiency of phenylalanine hydroxylase enzyme Classic PKU Atypical hyperphenylalaninemia Duo to deficiency of Duo to deficiency of cofactor enzyme Due to deficiency of BH4 Due to deficiency of Conversion of Phe to Tyr requires 1)CNS symptoms: phenylalanine hydroxylase symptoms tetrahydrobiopterin (BH4) Hence Phenylalanine is Mental retardation, failure to walk or Even if phenylalanine hydroxylase level accumulated talk, seizures, etc. is normal, the enzyme will not function
2)Hypopigmentation without BH4
Deficiency of melanin deficiency of BH4Caused by the Hydroxylation of tyrosine by deficiency of: tyrosinase is inhibited by high phe Dihydropteridine reductase conc. Dihydrobiopterin synthetase Carbinolamine dehydratase diagnosis Prenatal diagnosis is done by detecting gene mutation in fetus Neonatal diagnosis in infants is done by measuring blood phe levels
phe Phenylalanine hydroxylase * treatment Life long phe-restricted diet *not imp just memorize the names
Tyrosine so there will be no tyrosine Med432 Biochemistry Team Elevated phenylalanine in tissues, Characteristics plasma, urine of PKU
Gives urine a mousy odor In the absence or In the absence or deficiency of Because of > deficiency of BH 4 phenylalanine hydroxylase Phe is degraded to> 1& 2&3
Phe will not be converted to Tyr
No or less melanin Light skin in PKU patients Melanin 1 Melanin Tyr will not be converted to biosynthesis catecholamine (neurotransmitter) from tyrosine Synthesis of catecholamines 2 requires BH4
serotonin Trp will not be converted to serotonin (a 3
neurotransmitter) as it requires BH4 biosynthesis tryptophan from Tryptophan hydroxylase tryptophan Which required BH4 serotonin OTHER PIC s Amino acids involved Isoleucine, leucine and valine Tyrosine Tyrosine is involved in melanin production Place of In blood __ accumulation symptoms • mental retardation. • Hair and skin appear white. • physical disability . • Vision defects . • metabolic acidosis. • Photophobia. Clinical features Maple syrup odor . Melanin is absent types 1. Classic type: Most common, due to little or no activity __ of a-ketoacid dehydrogenase. 2. Intermediate and intermittent forms. 3. Thiamin-responsive form. treatment Limited intake of leucine, isoleucine and valine __ Med432 Biochemistry Team Disease Homocystinuria Alkaptonuria Enzyme Cystathionine β-synthase Homogentisic acid oxidase Amino acids involved Methionine Tyrosine and phenylalanine Place of accumulation In plasma and urine . in tissue and cartilage symptoms • Skeletal abnormalities. • Usually asymptomatic until adulthood • Osteoporosis. • Arthritis may will be seen • mental retardation. • displacement of eye lens. *is also associated with: 1. Neural tube defect (spina bifida) 2. Vascular disease (atherosclerosis) 3. Heart disease. Clinical features • High plasma and urine levels of homocysteine. • urine is oxidized to dark pigment over time. • Has a risk factor for atherosclerosis and heart disease. • Black pigmentation of cartilage, tissue. treatment 1. Oral administration of vitamins B6, B12 and folate. 1. Restricted intake of tyrosine. 2. Methionine-restricted diet 2. phenylalanine reduces homogentisic acid and dark pigmentation. Med432 Biochemistry Team 1 2 3 4 Med432 Biochemistry Team disease Defect Due to 1 Valine, Isoleucine,Leucine and deficiency of branched chain a-keto MSUD their keto acids accumulated. acid dehydrogenase leads to. Explanation 2 Absents of Melanin. Deficiency of tyrosinase. Albinism *Melanin biosynthesis from tyrosine. 3 Methionine and its Deficiency of cystathione b- Homocystinuria metabolites are synthase . accumulated . (homocystinuria / homocysteinemia) 4 Homogentisic aciduria (elevated deficiency of homogentisic acid Alkaptonuria homogentisic acid in urine) oxidase 1- In a patient with MAPLE SYRUP URNIE DISEASE there is a deficiency of enzyme … : A ) Tyrosinase B) Branched chain α-ketoacid dehydrogenase C) phenylalanine hydroxylase enzyme D) Homogentisic acid oxidase 2- The most obvious clinical feature in ALBINISM is : A) Tissue damage. B) Osteoporosis. C) Mental retardation. D) Melanin absence. Qs 3- The patient with HOMOCYSTINURIA may present with : A) Displacement of eye lens . B) Seizures . C) Metabolic acidosis . D) Vision defects . A --- 4- The doctor can treat Phenylketonuria (PKU) with : 4 A --- A) Life long phe-restricted diet. 3 D --- B) Intake of vitamin B6 . 2 B --- C) Intake of tyrosine . 1 Answers D) Intake of leucine. If you find any mistake, please contact us:) [email protected]