For All Medical & Allied Health Science Students

1. 1
By
N.Santhosh Kumar
Asst.Professor
Department of Biochemistry
SIMS & RH

2. Aromatic amino acid
Benzene group
Indole ring
Phenol group
Neutral, nutritionally essential, metabolically
both glucogenic and ketogenic
Neutral, nutritionally non essential,
metabolically glucogenic & ketogenic
amino acid
Neutral, Nutritionally essential,
metabolically both Glucogenic & ketogenic a.as

3. 3

4. Made For Each Other
• Tyrosine is synthesized from essential Phenylalanine, so diet should
contain sufficient phenylalanine
• Both are catabolized by Common pathway
• Form Fumarate and Acetoacetate, one goes to form Glucose and
other fat
• Tyrosine forms many imp substances & Both have significant
metabolic disorders

5. 5
Conversion of
Phenylalanine
to
Tyrosine
.
Hepatic enzyme
(p-OH phenylalanine)

6. • Phenylalanine is hydroxylated at para-position by phenylalanine
hydroxylase to produce Tyrosine (p-OH phenylalanine).
• This is an irreversible reaction and requires the participation of
a specific coenzyme Biopterin.
• The enzyme phenylalanine hydroxylase is present in the liver
6

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8. 8
DISORDERS
OF
PHYNYLALANINE
&
TYROSINE

9. Phenylketonuria
Incidence of PKU is 1 in 10,000 births
Deficiency of phenylalanine hydroxylase
Accumulation of Phe in tissues and blood, & results in its
increased excretion in urine

10. 10
Types of Phenylketonuria
Hepatic enzyme
Type -I,II & III PK
Type IV-PK
Type V

11. Effects on CNS system:
Mental retardation
Failure to walk or talk
growth retardation,
seizures and tremor
Excessive production of phenyl-pyruvate, phenyl-acetate, phenyl-lactate
and phenyl-glutamine. All these metabolites are excreted in urine in
high concentration.

12. Diagnosis:
– Urine and sweat of the affected individuals
smells like Mousy.
– by FeCl test (Dark green color/ ppt) and
tandem mass spectrometry method
– Guthrie test (newborn blood spot screening
‘heel prick’test ) used for routine neonatal test
for PKU
Treatment:
– Low phenylalanine in diet
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13. Neonatal tyrosinemia
Absence of
P-OH-phenyl-pyruvate dioxygenase
Temporary condition and usually responds to
Ascorbic acid.

14. 14
Alkaptonuria
Homogentisate accumulates in tissues, blood & is
excreted into urine
The defective enzyme is homogentisate oxidase

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(black / brown colored)
on standing
Alkapton bodies deposition occurs in
cartilages and joints resulting - Ochronosis
(arthritis)

16. Diagnosis:
 Change in color of the urine on
standing to brown or dark.
 The urine gives a +ve test with ferric
chloride (Dark Blue/Violet color ppt)
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17. Treatment
 It is lifelong condition (no specific treatment)
 High doses of Vitamin-C have been used to treat alkaptonuria.
 Because it hinders the accumulation and deposition of
homogentisic acid.
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Tyrosinosis Or Tyrosinemia Type -I
In acute tyrosinosis, the infant exhibits Diarrhea, Vomiting &
‘cabbage-like
Deficiency of the fumaryl acetoacetate hydroxylase /
maleylacetoacetate isomerase
Causes
Liver failure
Rickets
Renal tubular dysfunction
Poly Neuropathy

19. • A 5 yr old boy had delayed development and was unable to speak or
walk properly. There was a peculiar mousy odor noticed. He was found
to be mentally retarded with characteristic seizures and tremors. The
boy had a plasma phenylalanine level of 30 mg/dl (reference range of 1-
2 mg/dL) his urine gave positive ferric chloride test, indicating an
elevated excretion of phenylpyruvate.
Q: a) What is the probable diagnosis?
b) What is the biochemical defect?
c) What are the tests done to confirm the diagnosis?
19
Case Based Question-1
Textbook of biochemistry by Satyanarayana U; case-9; p771

20. Case Based Question-2
• A 6 month old infant was brought to NICU with complaints of
irritability, excessive cry, failure to thrive not gaining weight. Blood
investigations revealed– plasma phenylalanine level ˃20mg/dl.
Guthrie test was positive. Ferric chloride test showed blue green color.
Q: A. Identify the inborn error and enzyme defect the baby is suffering
from?
B:What dietary advice will you give to mother of baby?
C:Mention the biochemical test and confirmatory test for this disorder?
D:Mention the odor of the urine in this disorder
20
Wilma Delphine silvia et al. OSPE& CBL .Competency Based Practical Biochemistry Text book, 2nd ed.; case-8: p146

21. A 5 year old boy was brought to a Pediatrician with history of mousy odor
of urine and delay in achieving cognitive functions. On examination, the
boy's skin and hair was fair in color with hypo pigmentation.- 10M
Q: a: What is the probable diagnosis? 1M
b: Name the enzyme defect in the above disorder. 1M
c: Write the pathway for catabolism of the above amino acid 5M
d: Mention the reason for the cause of mousy odour in urine 1M
e: What biochemical tests are done to confirm the diagnosis?2M
21
Case Based Question-3
RGUHS University Theory Exam –Feb 2021)

22. A 5 year old female infant was hospitalized. A diagnosis of classic
phenylketonuria (PKU) was made.
Q: a. Name the defective enzyme of classic phenylketonuria.
b. Name the other types of phenylketonuria with their defective enzyme?
c. What are the characteristics of PKU?
d. Name diagnostic test for PKU?
22
Question-4
Textbook of biochemistry by Pankaja naik; p299

23. A 3 weeks old female infant was diagnosed to have Phenylketonuria
(PKU) .
Q: a. State the enzyme, which is most likely to be defective?
b. What is the screening test available ? Discuss the genetics of the
disease.
c. What are the characteristics of PKU?
d. What is the treatment given to the patient
23
Question-5
Rajesh K. Jambhulkar & Abhijit D N. Case Oriented Approach in Biochemistry:2019; p27

24. Case Based Question-6
• A 2 yr old female child was preferred with complaints of delayed milestones.
O/E mental retardation with low IQ units and the motor movements were
sluggish. Laboratory findings of Serum phenylalanine conc. is 30 mg% (normal
1-2 mg%), Urine ferric chloride test and DNPH test positive and TLC
chromatography phenylalanine shows ++++
• What is your diagnosis?
• Discuss the genetic basis of the disease.
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25. Case Based Question-7
A 20 year old young man came with complaints of back pain.
His urine gave positive Benedict’s test. On careful examination
his urine was found to turn blackish (coke-like) on standing.
The lab investigations revealed that he had normal FBS, PPBS
and serum uric acid levels.
Q: a) What is the probable diagnosis?
b) What is the biochemical defect?
c) What is the reason for positive Benedict’s test in urine?
25

26. Case Based Question-8
A 30 year old woman came with complaints of joint pain
blackening of ear pinna, tip of nose and blackening of urine on
prolonged exposure to air.
a: What is probable diagnosis?
b:Which is the enzyme defect in this condition?
c: Which vitamin supplement will reduce the symptoms?
d: What is ochronosis ?
26
Wilma Delphine silvia et al. OSPE& CBL .Competency Based Practical Biochemistry Text book, 2nd ed.; case-8: p147

27. • A mother admitted her child to hospital with c/o the diapers used for the child
stained black. Blackening of urine was observed on exposure. Laboratory
findings of Benedict's test and Negative for Glucose oxidase test. FeCl test with
urine gives +Ve. Silver nitrate test with urine gives Black color develops
immediately.
Questions:
a. What is the probable diagnosis?
b. What is the biochemical defect?
c. What are the complications of this disorder?
27
Case Based Question-9
Textbook of biochemistry by Pankaja naik;

28. Case Based Question-10
A 9year old child brought to the hospital with complains of black
discoloration of ear and nose. His urine turns black on standing. He
also had history of joint pain due to repeated arthritis.
Urine examination showed increased levels of homogentisic acid.
Q:
a: What is probable diagnosis?
b:Which is the enzyme defect in this condition?
C:What is ochronosis ?
28
Rajesh K. Jambhulkar & Abhijit D N. Case Oriented Approach in Biochemistry:2019; p32

29. Question-11
A patient was diagnosed as have alkaptonuria .
Q:
a: Outline the biochemical pathway. Name the metabolic defect that
caused this disease
b. Which is the pathway involved? Briefly explain this
c. State the changes in urine on standing in such patients
d:What is the possible treatment ?
29
Rajesh K. Jambhulkar & Abhijit D N. Case Oriented Approach in Biochemistry:2019; p33

30. Q:
a) What is the probable diagnosis?
b) Mention the biochemical defect
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Case Image -12

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Next presentation on
AAM-6b: Metabolic Functions of Phenylalanine & Tyrosine
Thank You