Metabolism — Flashcards

Flashcard 791: Describe the role of the following molecules in handling oxygen species and toxins: - Cytochrome oxidase - Cytochrome P450 - Myeloperoxidase - NADPH - Superoxide dismutase

Answer: • Cytochrome oxidase: Final component of the electron transport chain (Complex IV); reduces O2 to H2O, preventing the formation of reactive oxygen species (ROS). • Cytochrome P450: Involved in Phase I metabolism (hydroxylation) of endogenous compounds and exogenous drugs/toxins. • Myeloperoxidase: Found in neutrophil granules; converts H2O2 to HOCl (hypochlorous acid/bleach) during the respiratory burst to destroy pathogens. • NADPH: Provides reducing equivalents for both the generation of ROS (via NADPH oxidase) and the neutralization of ROS (via Glutathione reductase). • Superoxide dismutase: Neutralizes superoxide (O2•-) radicals by converting them into oxygen and hydrogen peroxide (H2O2).

Extra: NADPH is a critical cofactor. In the respiratory burst, it is used by NADPH oxidase to create superoxide. In cellular antioxidant defense, it is used by glutathione reductase to regenerate reduced glutathione, which then neutralizes H2O2. Chronic Granulomatous Disease (CGD) involves a deficiency in NADPH oxidase, leading to recurrent infections with catalase-positive organisms.

Flashcard 792: A 2 y/o boy comes to the office by his parents because they notice the boy urine turned black overnight. -Child has no significant past medical history, no medications. -Physical exam: well-nourished child with no swelllin or tenderness of any joints. -Urinalysis: Black urine -Which of the following conversion pathway is most likely deficient in this patient?

Answer: Tyrosine to fumarate due to deficiency of homogentisate dioxigenase enzymes, which cause accumulation of homogentisate. (Alkaptonuria)

Flashcard 793: What are the followings are associated with? -Heme oxygenase -Biliverdin reductase

Answer: Heme oxygenase: convert heme to biliverdin (green color) -Biliverdin reductase: convert biliverdin to bilirubin (yellow color)

Flashcard 794: A 5 month old boy comes with poor feeding. -Physical exam: hepatomegaly and hypotonia in all 4 limbs. -Cardiac auscultation: gallop rhythm -Chest Xray: Severe cardiomegaly -Muscle biopsy: Enlarged lysosomes containing periodic acid-schiff (PAS)-positive material. -Which enzymes is most likely deficient in this patient?

Answer: Acid alpha-glucosidase (alpha 1,4 glucosidase deficiency) or Acid maltase deficiency due to Pompe disease (Very Poor Carbs Metabolism) Accumulation of glycogen in lysosomal vesicles. Present with: Normal glucose levels, severe cardiomegaly.

Flashcard 795: what are the followings in association with 2,6 bisphosphate? -Acetyl COA ---> Fatty acids -Alanine ---> Glucose -Fructose-6-phophate ---> fructose-1,6-bisphosphate -Glucose----> glycogen -NAD ---> NADH

Answer: acetyl coa  ---> fatty acids: It will stimulate this reaction. Also occurs when you have insulin, which causes glucose to enter in cells in order to start glycolysis. glycolysis --> acetyl coa --> fatty acids. -Alanine ---> Glucose: occurs when you have 2,6 bisphosphate. It will inhibit this reaction because it doesn't want glucose present in blood. -Fructose-6-phosphate  ---> fructose-1,6-bisphosphate: It will stimulate this reaction to break down glucose in glycolysis. -Glucose ---> Glycogen: It will stimulate this reaction (similar to insulin) -NAD ---> NADH: It will stimulate this reaction, because of glycolysis.

Flashcard 796: Erythroblasts from a bone marrow biopsy  sample of a patient with Neonatal jaundice. -Cells are unable to generate NADPH from glucose metabolism. -But the cells are able to convert fructose-6-phosphate to ribose-5-phosphate, which is required for nucleic acid synthesis. -Which enzyme is essential for the latter conversion?

Answer: Transketolase or transaldolase due to fructose-6-phosphate conversion to ribose-5-phosphate, this reaction occurs in pentose phosphate pathway.

Flashcard 797: 22 y/o comes with 5 day history of Nausea, constipation, and severe, poorly localized abdominal pain. -She also reports anxiety, poor sleep quality and tingling of limbs. -She doesn't take any drugs,no smoking, medication or use alcohol. -Patient receives intravenous infusion of heme preparation that leads to rapid resolution of her symptoms. -The improvement in symptoms is most likely due to treatment-induced downregulation of what enzymes?

Answer: Aminolevulinate synthase (ALA Synthase) which is the rate limiting step in heme synthesis. Patient has Acute intermittent porphyria (recurrent abdominal pain, neuropsychosis symptoms) Symptoms: 5 P's: Port wine urine, polyneuropathy, painful abdomen, psychosis, precipitated by drugs (cytochrome p450) Glucose or heme makes better. (inhibits ALA synthase)

Flashcard 798: A 36 y/o man comes with dark urine and back pain. -patient ate some large, flat beans brought home by his wife after a business trip to egypt. -Physical exam: Jaundice & pallor. -Labs: hemoglobin 8g/dL. -Further evaluation reveals deficiency of an enzyme involved in the conversion of glucose-6-phosphate to ribulose-5-phosphate. -The substance generated during this conversion is necessary for which biochemical processes?

Answer: NADPH; used in fatty acid synthesis, steroid synthesis, and glutathione reduction. Diagnosis: Glucose-6-phosphate dehydrogenase (G6PD) deficiency.

Flashcard 799: 12 y/o male is evaluated for ataxia accompanied by episodic erythematous and pruritic skin lesions and loose stools. -Labs: Loss of neutral amino acids in the urine. -This patient's symptoms would most likely respond to what supplements?

Answer: Niacin (Vitamin B3) This patient has **Hartnup disease**, which is characterized by a defect in the transporter for **neutral amino acids** (like tryptophan) in the proximal renal tubule and enterocytes. Since tryptophan is a precursor for niacin, deficiency leads to **pellagra**-like symptoms: - Dermatitis - Diarrhea - Dementia (or ataxia in this case)

Flashcard 800: 1-day-old boy is diagnosed with hyperphenylalaninemia by newborn screening. - He's placed on a special phenylalanine-restricted diet with tyrosine supplementation. - Several months later, lab test results: normal serum phenylalanine level. - Careful examination: some neurological abnormalities. - Further workup: elevated prolactin. - Physician suspects a cofactor deficiency. - Which enzyme is most likely deficient in this patient?

Answer: Dihydrobiopterin reductase (BH2 reductase) This leads to a deficiency of BH4, which leads to PKU and high prolactin due to lack of dopamine from the same pathway.