Overview Notes (11) Related Modules

202 Proteins and 34

Amino acids

AROMATIC AMINOACIDS

Phenylalanine and tyrOsine: Structure 00:00:37

Pherjalanne Tyrosine

NH, -C- COOH Aanine AH-CcOOH

Berzere ring CH, Berzene ring
CH, +
one Hytrogen 6
rermoved ydroy
group (o)
hen
Pheroi ring
eSsential amino acid (AA) Dn essental amin acids

eoth Ketogenie 1gucogenic eoth hetogere 1ghucogenic

Non-polar amino acid Least non polar amorng non
polar aromotic amino acid

Phenylalanine & tyrosine: Metabolism 00:06:25

Phenyjalanine Tyrosine

Catabgje Anabolic
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tapubhuyan39332@gmailCs rarsanaseTyrosinase
netogenie Tyrosinase hydroulase
meianin catecholamines Thuroxine
ekoogenic
Phenyjaianne
(PAHhyaroxiyase
Pheralanne ’ Tyrosne
eTP cyciohyrolase Tetrahudro Dinydio
biopterin biopterin
Dihydrobiopter in redctase
NAOP NADPHH

Biochemistry vê0-Marrow 65-2023

Page 1/11
 34 Aromatic Amin
Acids
Properties of this reaction :
" ireversible reaction,

Phenyialanine hydroyases monooxygenase.

Concepts of henylalanine hydroxyase (PAH)
Lhenylalanine Turosine
Phyenylalanine is an essential amino acid,
Turosine is a non essential amino acid.

a. Phenyalanine doesn't have any tunction in the body

per se.
Hconverts into turosine and enters into a metabolic
pathuay
Catabolic fate of phenylalanine and tyrosine 00:14:06

Tyrosine transaminase
PAH PLP
Phenylalanine -’ Tyrosine ’ Parahydroxy
phenyl pyruvate
(PHPP)

a- hetoglutarate Glutamate PHPp

hydroxyjase
Vitamin C Ooxygenase)
Homogentisate
Iron (Fe) Homogentisate
Feedback Oxidase
; Oiogenase)
maleylacetoacetate
(mAA)
SH MAA cistrans
IsomeraSe
635975a7df22tbe2e5370d693
(FAA)
FAA
Khydrolase
Funarate Acetoacetate

Ghycogene tate hetogenie tate

Biochenistry v4.) " Macsw65 2023 Page 2/11

Overview Notes (11) Related Modules

204 Proteins and 34

Amino acids

Classic phenulketonuria :Defect in phenylalanine

hydroxjase (PAH).
" Non classic phenylketonuria type I I: Defect in
dhydrobioptern reductase.
Non classic phenylketoruria type v iVi Detect in
Pormation of tetrahydrobiopterin.
Akaptonuria :Defect in homogentisate oxidose.
635975á7df22be|e5370Ncgydrolase.
Tupe l tyrosinemia :Detect in tyrosine transaminase.
Type tyrosinemia :Defect in PHPP hydroxyase.
Phenylketonuria 00:22:54

PAH
Phenylalanine Tyrosine

Phenylalanine enters ito alternate metabolie pathway

Transamination Reduction
Phenylalanine >Phenylpyruvate >phenyi lactate
oxicdation
Phenul acetate
+alutamine Conjugation
Phenylacetygjutamine
Pheny acetote causes mousy bodyodour.
Tyrosine
OFeedback melanin Catecholamines Thyroxine
Hypopigmentotion Neurotransmitters

Blue eyes, blonde Neurological demcits :

hair, fair skin Agjtation, hyperacthvity
Some dietary tyrosine mental retardation
is converted to melanin.

Causes of neurolbqical manitestations

in the brain :Pherujalanine, tyrosine, tryptopBan passes
through the bood bain barrier throuoh a transorter.

Biochenistry y4G" Marrow6.6- 2023

Paqe 3/13
Overview Notes (11) Related Modules

34 Aromatic Amin/
Acids

In phenyhetonuria, phenyjalanine saturates al transporters.

‘ henyalanne, ltyrosine, i tryotoghan.

Phenulalanine cannot do any function as itis unabie to
convert to tyrosine.
Phenyalanine also preents dietary tuyrosine to enter
through the transporter.
Turosine: Neurotransmitters, catecholamines
Tryptophon : serotonin

Clinical Peature n intarts : ntractabie vomting,

misdlagnosed as congentaj pertroçhc yore stenosis.
Laboratory diagnosis and treatment of
phenylketonuria O0:33:34

. Guthrie's test (Bacteraj hbtion tes

Bacilus subtilis requres pherjalanne Por grouth.
Wphenulalanine preSent n biood : Bacteral cutures
Seen

In neonates, heel prick samcie taken.

a. Ferricchride uine test

tmi of fere choride addedto urinesample : Bue
qreen cokour ndicates a positive test.
Transient reaction

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D 3. elood phenyjalanine :
Normal:a-6 ma/d
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4. enzume studies Active
pace
S. Genetie mutotion studies.
a. Tandem mass spectrometryiold standard sereening
method for al metabolic disorders.

Treatment:
Restrict phenuialanine (cassava based diet).

Brocreiry Marow8E-023
Overview Notes (11) Related Modules

206 Proteins and 34

Amiro acids

" Concentrate of large neutral amino acid (LNA).

Saproptern dihydrochloride (uvani suynthetic e,
enzyme replacement therapy urder trial:
Phenylalanine ammonia lyase.
Alkaptonuria 00:40:11

Hormogentisoate >Benzoquinone
K HOmoaentisate Oxidase jPolymerise
may acetic acid (mAA) Akaptone bodies

Akaptone bodies acCumulate in nose, pinna f sclera : Black

spots.

Honogentsate excreted in urine, qets oxidised and

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in nfants, bac/ reddeh dseoloration of diaper.
inereased dseckoraton on uashnq with soap 'Alkalinization
inereases darenng of ure.
No mental retardator.
Cinical features: ach pain, black spots/ piamentation in
middle age
Ochronosis :Alraptone bodes accumulate in intervertebral
dises.

Garod's Tetrad Frst inborn error of metobolisn studied by

Archibald Garod

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D C- cystiria
A- Akaptonuria
A-Alonism
P-Pentosuria

Laboratory dngnosis:
Akalinisotion of urine: ‘ darkening of urine.
Ferric chior ide test :Positive.
AaNo test : Positive
x- ray spne :Parrot beak appearance.

Biochemistry " v4.0 Marrow 65 2023

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 Overview Notes (11) Related Modules

34 Aromatic Amin
Acids

Treatment :
Nitisinone/TBC: nhbits PHpp hydroxlase and reduces
horogentisate.

segaua sundrome:
Autosomal dominat.
Cincal Peatures : ustorna with deurnal variaton
635975va22be2e5370d693
TP Cyclohydrolase enzume is defectve.
Jen, but biood phenujaionne leveis nomal
Tyrosinemia 00:51:26

Type iturosinemia/Hepatorena eredtary trosineia.

atyrosinosis
most common type.
Hepatic and renal aáure.
enzyme defect iFuraryacetacetate hutroase
Accumukation of succin acetone.

LiNer laikre ’ mAT enzune aected

accumulation of methonne boled cabbage odour)
Resembie porphuri
Treatnent :itisinone.

Type i tyrosinemia :
A/WA ocutocutaneous turosinemia/eehrerharhart
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D suyndrome.
enzyme detciency : Turosine transaminase.
Clinical eatures i Coneal uicer,
Cutaneous non pruritic huper Keratotic plaque.
Active
pace

Tupe i tyrasnemia/ Neonatal tuyrosinemia iLeast comon

Hakinsinriai

mutation of PHPP hydroxuiase (partialy active).

aNes SAmmng pool odour.

BechestrytManow i5-202s
Page 6S
Overview Notes (11) Related Modules

208 Proteins and 34

Amino acids

Anabolic fate of tyrosine 00:56:57

I. Catecholamines:
Sunthesized in the chromafSin cells.

Adrenal -80% adreraline

Extra adrenal :Nor-epinephrine.
Nerve endings of sumpathetic ganglia.
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Tyrosine hydroxylase
oihydroay phenylalanine (oOP)
Dopa decarboxylase, PLP
Dopamine - ist catecholamine
Dopamine betaoxidase
Nor epinephrine
N-methy S-adenosymethionine
transferase s Sradenosuyhomocystene
epinephrine
S-adenosymethionine derived rom nethionine.

Copamine Nor epinephrine epinephrine

Catecho-o
methyjtransterase
Hoo voaniic acid Nor metanephrine metaneçhrine
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D monoamino Oxidase
Vanillumandelic acid (vmA)

a. melanin :
Sunthesized in melanosomes in melanocytes (deeper
layers of epidermis).

Eiochemistry v4.0 MarOw 6.5 2023

Page 7
Overview Notes (11) Related Modules

34 Aromatic Ami
Acids

Tyrosine
Tyrosinase (requries Cu)
ohydroy phenylalanine bOPa)

oopaqunone
Eumelanin Pheomelanin

3. Thyroxie:
Ssuynthesized in thyrogjobuin in throid folcles
Has IS turosine residues
f odinated: mit - onoiodo thonine
oIT -Diodo thayonne
Pheochromocytoma 01:08:01

Tumour of adreno] medulla

Excess catecholamines.
Symptoms :
rofuse sweating, headache, paptatons,hpertension.
Diagnosis :
a4 hr urinary examiation for
vanils
"
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Fractionated etanephrnes (hianiu serstve
In plasma, catechoiamines and free metanephrines.

Feedback
Question :A patient has "pil rolling" tremor, "coquwheel
a
rigidity, bradyhinesis, speech aiffcuties, anda shuffling gait.
The chemical that is lacking in this sundrome is a derivative
of which of the folowing amino acids ?
A Alanirne.
a. Serne. Actve
pa0e

C Tyrosine.
0. Tryptophan
Overview Notes (11) Related Modules e

210 Proteins and 34

Amino acids

Question : A4 month old infant normal at birth , developed

Sudden twitching movement she noticeda mousy body
odour in her wet diaper. She was taken to a pediatrician,
sample taken rom heel prick was send or Euthrie's
bacterial inhibition test.
O what is the probable diagnosis?
Phenylketonuria (PKD.
Qa what is the reason Por mousy body odour ?
Phenyl acetate.
q3)which is the amino acid eevated here?
Phenyl alanine.
Q4) what is the bacteria empbyed for this test ?
Bacillus subtilis.

Question :what is the rationale of using this Rx in PKu?

Ans in pherjiketorur ia, phenylalanine
saturates al transporters, thereby not
allouing tyrosine f tryptophan to enter
into the brain LNAA has high amount of
tyrosine, tryetoçhan Thus they are LNAA

strong enough to compete with

b35975a7df22be2e5370do9
Question :ASur okd bou presented with blue eues, blond hair,
fair skin, eczematous rash, unusual mousy odour torced to
eat ruits and other special diet.
Feedback
O

Answer i This is a case of Pheny ketonuria.

Overview Notes (11) Related Modules
34 Aromatic Amino 211
Acids

Question:A4 year old qiri presented to Pediatric OPD with

compiains of sudden weakness of both lower linbs
especially in the evening, but improes
n the morning, on investigation,
Tetrahydrobiopterin level is reduced,
but Phenuj Alanine level is normal.
what is your diagnosis ?
Ansuer iSegaua syndrome.
Question : ldertify this disorder assocated with catabolic
patthway oft phery aiarne ?

693975arLSnJd693
Answer iType Tyrosnema Gtyperher atotc plaques, Corneal
ulcer). AKa Oeulocutaneous turosnemia/icner harhart
syndrome.

Question:AGnonth uear dd bou presented with severe

metabolic acidosis, Ketosis, faure to ttrive and unusua
odour of sUiming pool as the weaning stoarted.
urine Tandem mass Spectrometry - HauKinsin
Feedback
D Answer :Haukinsuia

Active
pace

Biochemstry 0-Maros 65- 2Q23

Overview Notes (11) Related Modules

212 Proteins and 34

Amino acids

Blonde hair, fair skin, biue miky white hair, ore

eyes. depigmented/miky uhite
This is a case of PKu skin, red eyes. This is a
case of Albinism.

melanine sunthess s melanine sunthesis is

affected affected.

Turosine is less ’ Less Tyrosinase enzyme itset s

melanine. dehciert.

But dietary tuyrosine can be Even f dietary tuyrosine is

converted to melanin. present, it can ot be
converted to melanin.

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