Metabolism — Flashcards

Flashcard 841: A group of investigators is studying the regulation of catecholamines synthesis in response to severe stress. -The experimental animals are found subsequently to have decreased production of epinephrine by the adrenal medulla compared with the control animals. -Decreased activity of which enzymes is most likely responsible for the observed effect?

Answer: Phenylethanolamine-N-methyltransferase (PNMT) wihch usually stimulated by cortisol converted NE to Epi.

Flashcard 842: 23 y/o apparently healthy man who immigrated to the US comes to a clinic for regular check up. -History: no significant medical problems but his mother told him he was born with a problem metabolizing sugar. -Patient maintains no dietary restrictions and regularly eats vegetables, fruits, and meats. -Urine samples: Repeatedly positive copper reduction test. -Glucose oxidase dipstick test: negative -Which enzyme is most likely to be deficient in this patient?

Answer: Fructokinase (Essential fructosuria is a benign, asymptomatic condition where fructose is not metabolized by fructokinase but is instead excreted in the urine, giving a positive copper reduction test but a negative glucose oxidase test.)

Flashcard 843: Describe the clinical significance or deficiency symptoms associated with the following enzymes: A) Lactase B) Aldose reductase (in the context of galactose metabolism) C) Galactokinase D) Galactose-1-phosphate uridyltransferase (GALT) E) Phosphoglucoisomerase

Answer: A.) **Lactase**: Deficiency leads to **lactose intolerance** (bloating, cramps, osmotic diarrhea). Primarily occurs in adults; congenital form is very rare. B.) **Aldose reductase**: Converts galactose to **galactitol**. In GALK or GALT deficiency, galactose levels rise and are shunted to this pathway, causing galactitol accumulation in the lens and **cataracts**. C.) **Galactokinase (GALK)**: Deficiency leads to high galactose and galactitol, resulting in **infantile cataracts**, galactosemia, and galactosuria. D.) **Galactose-1-phosphate uridyltransferase (GALT)**: Deficiency causes **classic galactosemia**. Presents in neonates with vomiting, jaundice, hepatomegaly, cataracts, intellectual disability, and **E. coli sepsis**. E.) **Phosphoglucoisomerase**: Deficiency causes **hereditary non-spherocytic hemolytic anemia** due to a block in glycolysis.

Flashcard 844: 61 y/o man found unresponsive on a sidewalk. -He presents with breath smelling of alcohol. -He has agonal respirations and a pulseless EKG; he's pronounced dead on arrival. -Autopsy: necrosis is seen in the mammillary bodies and gray matter surrounding the 3rd & 4th ventricles. -This patient's brain findings are most likely associated with a decrease in what?

Answer: Erythrocyte transketolase activity Due to Wernicke-Korsakoff syndrome caused by thiamine (B1) deficiency. Thiamine serves as a cofactor for: - Pyruvate dehydrogenase - Alpha-ketoglutarate dehydrogenase - Branched-chain alpha-ketoacid dehydrogenase - Transketolase

Flashcard 845: The following conversion pathways are deficient in which metabolic diseases? - Leucine to acetoacetate - Phenylalanine to tyrosine - Tyrosine to fumarate

Answer: - **Leucine to acetoacetate**: Maple syrup urine disease (branched-chain α-keto acid dehydrogenase deficiency) - **Phenylalanine to tyrosine**: Phenylketonuria (phenylalanine hydroxylase deficiency) - **Tyrosine to fumarate**: Alkaptonuria (homogentisate oxidase deficiency)

Extra: These diseases involve blocks in the catabolism of amino acids: 1. **Maple Syrup Urine Disease (MSUD)**: Deficiency in the branched-chain α-keto acid dehydrogenase complex. Leads to build-up of Leucine, Isoleucine, and Valine. 2. **Phenylketonuria (PKU)**: Deficiency in phenylalanine hydroxylase (or BH4 cofactor). Phenylalanine cannot be converted to tyrosine. 3. **Alkaptonuria**: Deficiency in homogentisate oxidase, preventing the conversion of homogentisate (a tyrosine metabolite) into maleylacetoacetate, and eventually fumarate. Characterized by dark urine (on standing), ochronosis (pigment deposition), and arthritis.

Flashcard 846: What is the relationship of the following substances to pyruvate and lactic acid conversion? - Alanine - Asparagine - Galactose - Glycerol - Lysine - Serine

Answer: - **Alanine**: Converted to pyruvate via transamination (removing an NH3 group). - **Serine**: Converted to pyruvate. - **Asparagine**: Converted to aspartate and then to **oxaloacetate** (does not form pyruvate). - **Galactose**: Enters glycolysis; can be converted to pyruvate and then lactic acid (may be elevated in PDH deficiency). - **Glycerol**: Converted to glycerol-3-phosphate, then DHAP, which enters glycolysis to form pyruvate/lactic acid. - **Lysine**: **Cannot** be converted to pyruvate (Lysine and Leucine are the only purely ketogenic amino acids).

Flashcard 847: A scientist is studying a biochemical reaction that takes place in the liver. - He cultures hepatocytes with glutamate labeled with nitrogen isotopes. - After some time, he finds that the nitrogen isotopes are transferred to oxaloacetate, forming aspartate. - Which vitamin is most likely involved in this reaction?

Answer: Vitamin B6 (Pyridoxine)

Extra: This is a **transamination** reaction catalyzed by **Aspartate Aminotransferase (AST)**. All transamination reactions require **Pyridoxal Phosphate (PLP)**, the active form of **Vitamin B6**, as a cofactor. In this reaction, the amino group from glutamate is transferred to the alpha-keto acid oxaloacetate to form aspartate and alpha-ketoglutarate.

Flashcard 848: What are the roles of the following enzymes in catecholamine metabolism? - Catechol-O-methyltransferase (COMT) - Monoamine oxidase (MAO) - Phenylethanolamine-N-methyltransferase (PNMT)

Answer: • **COMT & MAO**: Involved in the **degradation** (breakdown) of catecholamines. • **PNMT**: Involved in the **synthesis** of epinephrine (converts Norepinephrine to Epinephrine).

Flashcard 849: A deficiency of the following enzymes will lead to what disease? -Delta- aminolevulinate dehydratase -Delta-aminolevulinate synthase -Cystathionine synthase -Glucose-6-phosphate dehydrogenase -Pyruvate kinase

Answer: D ALA dehydratase: Lead poisoning -D ALA synthase: Sideroblastic anemia -Cystathione synthase: usually convert homocystine to cystathionine (with help of B6), thus lead to homocystinuria. -G6PD: hemolytic anemia -Pyruvate kinase: (autosomal recessive disease) Hemolytic anemia.

Flashcard 850: 22 y/o man comes with recurrent blistering on the back of his hands and forarms for the past several years. -He has used overcounter meds, but symptoms didn't improve. -He has no exposure to chemicals or animals -Physical exam: vesicles and erosions on the dorsum of both hands. -Which enzymes is most likely deficient in this patient in relation to heme synthesis pathway?

Answer: Uroporphyrinogen decarboxylase because patient present with skin blistering (photosensitivity) due to Porphyria cutanea tarda (PCT)