Metabolism — Flashcards

Flashcard 851: 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 852: 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 853: 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 854: 6 month old full term boy comes with lethargy and vomiting. -Patient was breastfed exclusively until 2 days ago when homemade purred food was added to his diet. -Serum glucose: 30 mg/dL. -Dx: confirms aldolase B deficiency. What should be removed from this patient's diet?

Answer: Sucrose or fructose due to aldolase B deficiency (sucrose: glucose+fructose) fructose --> fructose 1 phosphate by fructokinase. Fructose 1-phosphate ---> glyceraldehyde by aldolase B. Aldolase B deficiency: Fructose intolerence Fructokinase defect or deficiency: Essential fructosuria

Flashcard 855: The following supplements are useful in what disease or mechanism? -Arginine -Cobalamin -Pyridoxine -Tetrahydrobiopterin -Thiamine

Answer: - Arginine: Used in urea cycle disorders (to facilitate nitrogen excretion). - Cobalamin (B12): Used in megaloblastic anemia and hyperhomocysteinemia. - Pyridoxine (B6): Used in hyperhomocysteinemia. - Tetrahydrobiopterin (BH4): Used in BH4 deficiency (a cause of phenylketonuria), as it is a cofactor for phenylalanine hydroxylase. - Thiamine (B1): Used in Maple syrup urine disease (MSUD), Wernicke-Korsakoff syndrome, and Beriberi (Wet/Dry).

Flashcard 856: A 6-month-old boy is brought to the office because he is not developing normally. - Physical exam: delayed developmental milestones and hypotonia. - He has a tendency to aggressively bite his own lips and fingers. - Labs: Elevated blood uric acid level. Activity of what enzyme is most likely increased in this patient?

Answer: PRPP amidotransferase (Glutamine-phosphoribosyl amidotransferase) This patient has **Lesch-Nyhan syndrome**, which is caused by a deficiency of **HGPRT**. In HGPRT deficiency, the activity of **PRPP amidotransferase** (the rate-limiting enzyme of *de novo* purine synthesis) increases due to: 1. Increased availability of **PRPP** (substrate). 2. Decreased levels of **IMP** and **GMP** (loss of feedback inhibition). **HGPRT** mnemonic: **H**yperuricemia **G**out **P**issed off (aggression/self-mutilation) **R**etardation dys**T**onia (and choreoathetosis)

Flashcard 857: In what reactions do the following amino acids participate? - Phenylalanine - Valine - Asparagine - Histidine - Proline - Lysine

Answer: - **Phenylalanine**: Converted to tyrosine by **phenylalanine hydroxylase**. Deficiency of this enzyme leads to PKU. - **Valine**: Part of the "VOMIT" pathway (Valine, Odd-chain fatty acids, Methionine, Isoleucine, Threonine); these synthesize **propionyl-CoA**, which converts to methylmalonyl-CoA (via propionyl-CoA carboxylase) and then to **succinyl-CoA** (via methylmalonyl-CoA mutase). - **Asparagine**: Converted to aspartate by **asparaginase**. Leukemic cells require asparagine for survival, so L-asparaginase is used as an antineoplastic agent. - **Histidine**: Converted to **histamine** (via histidine decarboxylase), which is released by mast cells in Type 1 hypersensitivity and stimulates gastric acid secretion. - **Proline**: Converted to **glutamate**, which can then be converted to $\alpha$-ketoglutarate. It is also **hydroxylated** by Vitamin C during collagen synthesis. - **Lysine**: Strictly **ketogenic**. Like proline, it is **hydroxylated** by Vitamin C during collagen synthesis.

Flashcard 858: What is the clinical or metabolic significance of the following enzymes? - Bisphosphoglycerate mutase - Hexokinase - Pyruvate kinase - Transketolase

Answer: • Bisphosphoglycerate mutase: Synthesizes 2,3-BPG in RBCs (Rapoport-Luebering shunt), which decreases Hb affinity for O2 and facilitates oxygen unloading to tissues. • Hexokinase & Pyruvate kinase: Glycolytic enzymes; deficiency leads to hemolytic anemia. • Transketolase: Pentose Phosphate Pathway enzyme that requires thiamine (B1) as a cofactor. It converts ribose-5-phosphate to fructose-6-phosphate. RBC transketolase activity is decreased in thiamine deficiency.

Flashcard 859: 12 y/o patient presents with severe chest pain. - He has had intermittent substernal chest pain for the past few months, occurring after heavy activity. - BP: 130/80 Pulse: 132/min RR: 24/min - Physical exam: Anxious appearing boy with rapid but regular pulse. - Troponin is elevated. ECG reveals ST segment elevations in leads II, III, & aVF. - Further lab results: Increased serum methionine level. - Which amino acid is most likely essential in this patient?

Answer: Cysteine Due to homocystinuria, which leads to premature thromboembolic events such as atherosclerosis and acute coronary syndrome.

Flashcard 860: A 6 month old girl comes with mother due to lack of growth despite feeding. -Physical exam: Hepatomegaly, hypotonia, height & weight below the 10th percentile. -Lab: Hypoglycemia, ketoacidosis -Liver biopsy: hepatic fibrosis without fat accumulation. -Which enzymes is most likely deficient in this patient?

Answer: Debranching enzyme (alpha 1,6-glucosidase) due to Cori disease. Present with Hepatomegaly, hypoglycemia, hypotonia without cardiomegaly.