May 22, 2023
Phenylalanine is converted to tyrosine (hydroxylated phenylalanine) catalyzed by phenylalanine hydroxylase.All hydroxylases are monooxygenases. Every hydroxylase will allow an oxygen molecule to react with the substrate. When an oxygen molecule reacts with Phenylaniline, one 'O' of the oxygen molecule will be incorporated into the substrate. Finally, the substrate is converted to the hydroxylated form. The other O will become water (hydrogen atoms are obtained from the co-enzyme tetrahydrobiopterin (BH2) that is converted to dihydrobiopterin)
Phenylalanine on Transamination forms phenylpyruvate. Phenylpyruvate on reduction becomes phenyl lactate.
On reduction, it is converted to phenylacetate. Phenylpyruvate (phenyl ketone) on oxidative decarboxylation forms phenylacetate. It reaches the liver and undergoes conjugation with glutamine (phenylacetylglutamine) excreted through urine.
|Tyrosine (hydroxy phenylalanine) converted to P hydroxy phenylpyruvate||Tyrosine transaminase.|
|P hydroxy phenylpyruvate to homogentisic acid.||P hydroxy phenylpyruvate dioxygenase|
|Homogentisic acid is converted to maleylacetoacetate||Homogentisate oxidase|
|Maleylacetoacetate to fumarylacetoacetate.||Cis trans isomerase|
|Fumarylacetoacetate is converted to fumarate and acetoacetate||Fumarylacetoacetate hydrolase|
There is Deficiency of the enzyme Fumarylacetoacetate hydrolase. Fumarylacetoacetate (precursor) accumulates which is toxic to both liver and kidney parenchymal cells (Fanconi syndrome progresses to renal failure). It results in jaundice, hepatomegaly, hypoglycemia, HCC and liver cirrhosisFanconi ,syndrome,Renal failure. Additionally, Fumarylacetoacetate is converted to succinyl acetone that inhibits the delta ALA dehydratase (heme synthetic enzyme). Elevation of succinyl acetone is considered as a pathognomonic feature. Many times, this disease is misdiagnosed as porphyria (due to neuropsychiatric manifestations).
Also known as Occulo cutaneous syndrome, Richner-Hanhart syndrome. In this there is Deficiency of enzyme: Tyrosine transaminase.Ocular changes which we are present are Painful corneal erosions and Cutaneous changes which are present are Palmar hyperkeratosis.
In this there is Deficiency of enzyme P hydroxy phenylpyruvate dioxygenase.it can be seen in patients with Recurrent seizures, intermittent ataxia. Gain of function mutation of P hydroxy phenylpyruvate dioxygenase causes hawkinsinuria (swimming pool odor of urine).
There is Deficiency of Homogentisate oxidase. Homogentisic acid will be accumulated in the blood (undergoes oxidation to form benzoquinone acetate. It polymerizes to form melanin-like fibers (pigmentation of the skin, mucus membrane).
Osler's sign: Black or brown pigmentation of sclera between the medial and lateral rectus (sign) It accumulates in cartilage (cartilage destruction). Finally, it causes ochronosis (a feature of Alkaptonuria). Patients are normal till mid-age. Indications are multiple joint involvements, multiple intervertebral disc bulges, knee pain.Symptom include Urine turns dark on standing. Treatment is done by inhibiting the oxidation (antioxidants: Vitamin C, Nitisinone)
Acts by inhibiting P hydroxy phenylpyruvate dioxygenase. Loss of gene mutations causes type-III tyrosinemia. Gain of function mutation causes hawkinsinuria. This drug was first used in the treatment of type-I tyrosinemia. Because when this enzyme is inhibited, the precursor fumarylacetoacetate is not formed. Hence, not toxic to liver and kidney parenchymal cells. It is used To treat alkaptonuria (accumulation of homogentisic acid is inhibited) and To treat hawkinsinuria. It is contraindicated in Type-II tyrosinemia
|Tyrosine to dihydroxy phenylalanine (DOPA)||Tyrosine hydroxylase|
|DOPA to Dopamine||DOPA Decarboxylase (uses PLP as a coenzyme)|
|Dopamine gives Norepinephrine||Dopamine beta-hydroxylase (depends on Vitamin C)|
|Norepinephrine forms epinephrine||S adenosyl l methionine|
Synthesis of Melanin Pigment
|Tyrosine to DOPA||Tyrosine hydroxylase/ Tyrosinase|
|DOPA to Melanin||Non-enzyme-catalyzed chemical reaction|
Thyroid gland is organized in the form of follicles (have a central colloid). It is surrounded by a layer of follicular cells (active protein synthesizing machinery). Protein: Thyroglobulin (synthesized)
|T3 (the active form of thyroid hormone)||Less|
Also Read : Electron Transport Chain
It occurs due to Defect in Phenylalanine metabolism (major fate- Phenylalanine hydroxylase)
Take a colony plate of Bacillus subtilis.
Add drop of patient’s blood
After incubating, count the number of colonies.
There is steady state increase of bacillus subtilis.
It indicates the presence of phenyl ketones in the blood
|Fruity||DKA (diabetic ketoacidosis)|
|Cabbage||Tyrosinemia (type I)|
|Oast house (urine and sweat smell as oasthouse) or beer baby syndrome||Methionine malabsorption|
|Sweaty feet||Isovaleric acidemia|
|Tom cat Urine||Multiple carboxylase deficiency|
|Fish odor||Trimethyl amine urea|
This is everything that you need to know about phenylalanine and tyrosine metabolism for your biochemistry preparation. For more interesting and informative blog posts like this download the PrepLadder App and keep reading our blog!
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