VBC607 UnitI PG 31102020 DEFECT IN AMINO ACID CATABOLISM Phenylketonuria Deficiency of phenylalanine hydroxylase or a defect in biosynthesis reduction of tetrahidrobiopterin ID: 915928
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Slide1
Diseases of Amino
Acid Metabolism-I
VBC-607
Unit-I
P.G.
31.10.2020
Slide2DEFECT
IN
AMINO ACID CATABOLISM
Slide3Phenylketonuria
Deficiency of phenylalanine hydroxylase or a defect in biosynthesis/ reduction of
tetrahidrobiopterin
Urinary excretion of phenlypruvate and phenyllactateDefective neural developmentSevere mental retardationVery light skin pigmentationUnusual gait, stance, sitting posture High frequency of epilepsyAutosomal recessive
Slide4Cause
PKU is caused by a defect in the gene that helps create phenylalanine hydroxylasePhenylalanine hydroxylase :Mixed function oxidase that uses cofactor (tetrahydrobiopterin ) and molecular oxygen
Unable to break down phenylalanine.This causes a buildup of phenylalanine in the bodySymptom
sSeizuresTremors, or trembling
and shakingStunted growthHyperactivity
A musty odor of
their breath, skin, or u
rine
Slide5In patients with PKU,
Phenylalanine undergoes transaminaton with pyruvate to yield phenyl pyruvate.
Phenylpyruvate is either decarboxylated to phenylacetate or reduced to phenylactate.
Phenylacetate imports a characteristic odor to urine.
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Slide6Treatment/ Precautions
Avoid foods high in protein
Diet restricted in phenylalanine but supplemented with tyrosineNatural proteins, such as casein of milk, must be first hydrolyzed and phenylalanine removedFoods sweetened with aspartame should be avoidedMedication- Sapropterin (Kuvan) for the treatment of
PKU. Sapropterin helps lower phenylalanine levels
Slide7When there is a defect in the enzyme that catalyzes the regeneration of tetrahydrobiopterin, diet must be supplemented with L-dopa and 5-hydroxytryptophan (precursors of neurotransmitters norepinephrine and serotonin respectively)
Supplementing diet with tetrahydrobiopterin is ineffective because it is unstable and does not cross the blood-brain barrier.
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Slide8Alkaptonuria (Black urine disease)
Lack of
Homogentisate
1,2 dioxygenase Homogentisic acid accumulates and is excreted in the urine.This compound oxidizes on standing or on treatment with alkali, gives the urine a dark colorautosomal recessivesymptoms start in 3 rd/4 th decade relatively benign in comparison to PKUalkaptonuria was not only the first characterized inborn error of metabolism but the first ever disease identified as being
inherited.
Slide9Deposition of dark (ochre-colored)pigment in cartilage tissue severe arthritis
connective tissue pigmentation(ochronis)
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Slide10Alkaptonuria
Slide11Characteristic of Alkaptonuria
Homogentisic aciduria
Ochronosis (a bluish-black discoloration of tissues) and
Dark spots in the sclera (white) of eyes
Thickened and darkened cartilage in ears
Blue speckled discoloration of skin, particularly around sweat glands
Black earwax
Kidney stones and prostate stones
Arthritis (especially hip and knee joints)
The exact mechanisms by which alkaptonuria results in ochronosis and arthritis are still not fully understood.
Slide12Treatment
A low-protein diet.
large doses of ascorbic acid, or vitamin C, to slow down the accumulation of homogentisic acid in cartilage.
Physical and occupational therapy may help to maintain flexibility and strength in muscles and joints.Use of the drug nitisinone as a possible treatment for alkaptonuria
Slide13Alkaptonuria
and Phenylketonuria
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