Tyrosine metabolism

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Which enzyme deficiency causes hereditary tyrosinemia type 1
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Which enzyme deficiency causes hereditary tyrosinemia type 1
Fumaryl-acetoacetate hydroxylase.
A 3 year-old child presents with diarrhoea and vomiting after high protein diet.He has history of multiple neuronal crisis in the past.His examination reveals icterus and cabbage like odor. His laboratory investigations are significant for deranged liver and renal function test and rickets.Increased serum and urinary succinylketone levels are seen. He is diagnosed with type I tyrosinemia. He is at increased risk of developing which one of the following?
Hepatocellular cancer
Obesity
Diabetes
Increased fumarylacetoacetate and maleylaceotacetate are alkylating agents and lead to tumorigenesis. ( Hepatocellular cancer)
Which enzyme deficiency causes type II Tyrosinemia?
Tyrosine transaminase
Which enzyme deficiency causes neonatal tyrosinemia
p-hydroxyphenylpyruvate hydroxylase
Which tyrosinemia is also referred to as oculocutaneous tyrosinemia
Type II tyrosinemia
Which type of tyrosinemia is associated with increased risk of hepatocellular cancer?
Type 1 tyrosinemia
What is the other name of black urine disease
Alkaptonuria
Which enzyme deficiency causes alkaptonuria?
Homogentisic acid 1-2, dioxygenase/homogentisic acid oxidase/homogentisate oxidase
A 50-year-old man presents with greyish blue papules on extensor surface of 2nd finger of both hands for last 1 year.He complained of darkening of urine for last 20 years with recent worsening.He is obese and hypertensive , currently using antihypertensive.He already underwent many orthopedic procedures as knee arthroscopy,Lumbar spine arthrodesis ( lumbar spine fusion done for low back pain and degenerative spine diseases) and achillis tendon rupture repair.Family history , his sister presented with coca-cola color in her diapers in early childhood.His dermatological examination reveals multiple greyish spots in sclera, periuretheral hyperpigmentation and generalized bluish grey pigmentation of all the nail beds. What is most likely causing pigmentation and his problems?
Oxidized derivatvies of homogentisic acid

In alkaptonuria, homogentisic acid accumulates and is oxidized to quinone form.
- It gets deposited in skin ( blue papules, periuretheral hyperpigmentation, generalized pigmentation of nail beds), joints pain ( the reason for knee arthroscopy, spine surgery likely due to persistent back pain and degeneration of intervertebral disc)
- Coca-color diapers in sister indicative of familial disease.
- History of dark urine for last 20 years

(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4155960/)
Image: A 50-year-old man presents with greyish blue papules on extensor surface of 2nd finger of both hands for last 1 year.He complained of darkening of urine for last 20 years with recent worsening.He is obese and hypertensive , currently using antihypertensive.He already underwent many orthopedic procedures as knee arthroscopy,Lumbar spine arthrodesis ( lumbar spine fusion done for low back pain and degenerative spine diseases) and achillis tendon rupture repair.Family history , his sister presented with coca-cola color in her diapers in early childhood.His dermatological examination reveals multiple greyish spots in sclera, periuretheral hyperpigmentation and generalized bluish grey pigmentation of all the nail beds. What is most likely causing pigmentation and his problems?
What is ochronosis?
Oxidized homogentisic acid deposits in bones, connective tissues, sclera, skin and elsewhere in body
What are clinical manifestation of alkaptonuria?A slate grey or bluish black pigment is deposited in different tissues and it causes the following: - blue/greyish discoloration of eye, ear cartilage - arthritis of hip and knee - low back pain due to degeneration of intervertebral disc i - aortic and mitral valve stenosis - tendons rupture easily - Coronary artery calcifications - renal stonesWhat is the chemical nature of pigment deposited in alkaptonuriaQuinone derivative formed from autoxidation of homogentisic acidWhat is treatment of alkaptonuria- Vitamin C in high doses - increases excretion of homogentisic acid and its oxidized metabolite in urine - Nitisinone ( inhibitor of p-hydroxyphenylpyruvate) inhibits homogentisate formation. - Decreased tyrosine intake in dietA 50-year-old man presents with severe lower back pain for past few years. Back pain is 10/10 in intensity, radiates to bilateral lower legs, achy in quality, associated with motor weakness in bilateral lower legs and numbness and tingling sensation. Back pain has been worsening ever since it started.He has had dark urine for past many years as well.On examination, there are multiple scattered greyish blue papules in his skin of hands and feet, on sclera , ear cartilage and his nail beds. Which enzyme deficiency is present in this man?He has alkaptonuria based on - dark urine for many years greyish blue pigmentation back pain Homogentisate oxidase is absentA 30 year-old symptomatic healthy man gives his urine sample for drug screening for job employment. Lab tech observes that urine sample turns black on standing . What is enzyme deficiency present/diagnosis?Alkaptonuria Homogentisate oxidaseyes/no Catecholamines are specialized end products of L tyrosineyesWhich enzyme catalyzes rate limiting step for synthesis of epinephrine from L tyrosine and what is the coenzyme that is required for the same enzyme?Tyrosine hydroxylase Tetrahydrobiopterin is the coenzyme required for the itWhich vitamins are required for epinephrine /Catcholamine synthesis from L tyrosine ?PLP for dopa decarboxylase ( Dopa---> Dopamine) Vit c for dopamine beta oxidase Vit b12 and Folic acid for SAM formationWhat is the nature of reaction converting Norepinephrine to epinephrineMethylation reaction ( SAM is the methyl donor)Which enzyme converts Norepinephrine to EpinephrinePhenylethanolamine N methyl transferase ( PNMT)Which hormone is responsible for epinephrine content of adrenal medullaCortisol increases transcription of PNMT ( Phenylethanolamine N methyl transferase) which converts more and more norepinephrine to epinephrine. Hence, the epinephrine content of adrenal medulla is 80 % and norepinephrine content is 20 %A 40-year old man present with episodes of tachycardia, hypertension, palpitations, headaches. He also complaints of weight loss of 10 pounds over last 6 months. CT scan shows a mass in left adrenal gland and a diagnosis of pheochromocytoma is suspected. Serum catecholamine and metanephrine levels are increased due to increased production by tumor. You order for urinary concentration of the products of catcholamine metabolism which are.......,......Vanillyl mandelic acid, metanephrines Elevated catcholamines and metanephrines are cornerstone of diagnosis of pheochromocytomas. Note : Pheochromocytoma is a catecholamine producing tumor of adrenal medulla and Diagnosis is made by measuring serum /urinary catecholamines and their metabolites metanephrines.What are the enzymes invovled in degradation of catcholamines and where are they foundMonoamino oxidase ( in most cells) Catcehol O methyl transferases ( primarily in liver and also in neurons)which enzyme is deficient in albinos?copper dependent tyrosinaseyes /NO Tyrosine hydroxylase present in melanocyte requires tetrahydrobiopterin as its coenzymeNo Tyrosinase ( Tyrosine Hydroxylase) present in melanocytes doesnot require tetrahydrobiopterin. It synthesizes melanin and is copper dependent in contrast, tyrosinase present in adrenal medulla requires tetrahydrobiopterin and forms dopa from tyrosineyes/no Deficiency of Tyrosine Hydroxylase enzyme in melanocytes predisposes to skin canceryes Deficiency of Tyrosine hydroxylase in melanocytes leads to albinism .People with albinism are at increased risk of skin cancer due to absence of melanin. Melanin blocks UV rays of sun and prevents DNA damage in the skin.A 30-year-old man with history of major depression comes to your clinic with the complaints of tachycardia, excessive sweating, headache and palpitations.According to him, symptoms started this afternoon after he went on a colleagues farewell party. He feels he ate a lot as the menu was extensive and consisted mainly of fermented sausages as peperoni and salami , rice, yogurt, chicken and beef liver and pizza with added cheese etc. Currently he is taking phenelzine ( MAO inhibitor for Depression), Rantidine ( for dyspepsia) On examination , BP is 140/90 mm Hg, Heart rate is 100/min, RR is 14/min and Temp 98.7. What is responsible for his symptomsThis man is showing cheese effect. MAO inhibitors react with cheese /fermented foods and lead to sympathomimetic effects.Which amino acid is responsible for cheese effectTyrosineWhich are the foods rich in tyraminePickled /fermented/marinated meat Added Cheese WineWhy MAO-inhibitors lead to cheese effectCheese is rich in tyramine , which is metabolized in our body by MAO-A If a person is consuming MAO-A Inhibitor, it inhibits the metabolism of tyramine which leads to norepinephrine release and sympathetic system stimulation and causes - tachycardia, increased BP, Palpitations, excessive sweating and headache.