Metabolism — Flashcards

Flashcard 831: 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 832: Identify the required vitamin cofactors for the following metabolic reactions: - Glucose to ribose-5-phosphate - Pyruvate to acetyl-CoA - Pyruvate to alanine - Pyruvate to oxaloacetate - Succinate to oxaloacetate

Answer: - Glucose to ribose-5-phosphate: Niacin (B3) for NADPH production. - Pyruvate to acetyl-CoA: Thiamine (B1), Riboflavin (B2), Niacin (B3), Pantothenic acid (B5), and Lipoic acid (Cofactors for Pyruvate Dehydrogenase). - Pyruvate to alanine: Vitamin B6 (Pyridoxine) for ALT (transamination). - Pyruvate to oxaloacetate: Biotin (B7) for Pyruvate Carboxylase. - Succinate to oxaloacetate: Riboflavin (B2) for Succinate Dehydrogenase (FAD) and Niacin (B3) for Malate Dehydrogenase (NAD+).

Flashcard 833: what are the followings in relation to Phenylalanine metabolism? -Dihydrobiopterin reductase -Dopamine B-hydroxylase -Dopamine decarboxylase -Phenylalanine hydroxylase -Phenylethanolamine N-methyltransferase -Tyrosinase

Answer: Dihydrobiopterin reductase: convert BH2 to BH4 in order to use BH4 as a cofactor to convert phenylalanine to tyrosine. -Dopamine B-hydroxylase: convert dopamine to norepinephrine. Requires Vit. C as cofactor. -Dopamine Decarboxylase: convert DOPA to dopamine. Requires Vit. B6 as cofactor. -Phenylalanine hydroxylase: convert phenylalanine to tyrosine. Requires BH4 as cofactor. -Phenylethanolamine N-methyltransferase: convert norepinephrine to epinephrine. Requires SAM as cofactor. -Tyrosinase: convert tyrosine (DOPA to melanin). Tyrosinase deficiency will cause albinism.

Flashcard 834: 18 y/o girl with type 1 DM comes with several hours of nausea, vomiting and abdominal pain. - Breath: fruity odor - Glucose: 452 mg/dL & high anion gap metabolic acidosis. - Increased activity of what enzyme is most likely contributing to this patient's abnormal blood glucose finding?

Answer: Glycerol kinase It converts glycerol (released from adipose tissue during lipolysis) into glycerol 3-phosphate in the liver, which is then used as a substrate for gluconeogenesis.

Flashcard 835: Which of the following reactions is a step in **gluconeogenesis**? - Acetoacetyl CoA → HMG-CoA - Acetyl CoA → Palmitic acid - Fructose 6-phosphate → Fructose 1,6-bisphosphate - Glycogen → Glucose-1-phosphate - Oxaloacetate → Phosphoenolpyruvate

Answer: Oxaloacetate → Phosphoenolpyruvate **Explanation:** - **Oxaloacetate → Phosphoenolpyruvate**: Catalyzed by PEP carboxykinase (PEPCK); a key regulatory step in **gluconeogenesis**. - **Acetoacetyl CoA → HMG-CoA**: Part of ketogenesis (mitochondria) or cholesterol synthesis (cytosol). - **Acetyl CoA → Palmitic acid**: Part of fatty acid synthesis (lipogenesis), which occurs in the well-fed state. - **Fructose 6-phosphate → Fructose 1,6-bisphosphate**: The rate-limiting step of **glycolysis** (catalyzed by PFK-1). - **Glycogen → Glucose-1-phosphate**: The process of **glycogenolysis**; liver glycogen is typically depleted after 12–24 hours of fasting.

Flashcard 836: A 34-year-old man presents with a facial injury. - He reports getting hit on the face during a fistfight. - Physical exam: Dark blue periorbital ecchymosis on the right side. - Ophthalmic & neurologic examinations are otherwise normal. - The patient is discharged home, but several days later the bruise becomes greenish in color. - This change in color is best explained by the activity of which enzyme?

Answer: Heme oxygenase A bruise (ecchymosis) changes color as hemoglobin is degraded: 1. Heme (purple/blue) is converted to Biliverdin (green) by **Heme oxygenase**. 2. Biliverdin is then converted to Bilirubin (yellow) by **Biliverdin reductase**.

Flashcard 837: What are the following amino acids? -Alanine -Aspartate -Histidine -Arginine -Glutamine

Answer: • Alanine & Aspartate: Glucogenic amino acids. Alanine is metabolized in the liver to pyruvate. Aspartate converts to oxaloacetate. • Histidine: Precursor to histamine, which stimulates gastric acid secretion. • Arginine: An intermediate in the urea cycle, facilitating the removal of ammonium (NH4+) from the blood. • Glutamine: Converted to glutamate to produce NH4+ and HCO3- in the kidneys to compensate for metabolic acidosis.

Flashcard 838: What are the following associated with? - Ascorbic acid - Carnitine - Pyridoxine - Thiamine - Tyrosine - Vitamin K

Answer: - **Ascorbic acid (Vit C):** Cofactor for hydroxylation of proline and lysine (collagen synthesis); deficiency causes scurvy. - **Carnitine:** Required for long-chain fatty acid transport into the mitochondria. - **Pyridoxine (Vit B6):** Cofactor for transamination; supplement in B6-responsive homocystinuria (presents with Marfanoid habitus). - **Thiamine (Vit B1):** Deficiency leads to Wernicke-Korsakoff syndrome, Beriberi, and Maple Syrup Urine Disease (cofactor for BCKDH). - **Tyrosine:** Precursor for catecholamines (dopamine, epinephrine, norepinephrine). - **Vitamin K:** Required for post-translational gamma-carboxylation of clotting factors II, VII, IX, and X.

Flashcard 839: 11 y/o girl is evaluated for blurry vision. - Physical Exam: bilateral lens opacities -Urine is positive for reducing substances. -Deficient activity of which enzyme is the most likely cause of this patient's eye condition?

Answer: Galactokinase

Extra: Galactokinase deficiency leads to the accumulation of galactose, which is shunted into an alternative pathway where it is converted to **galactitol** by the enzyme **aldose reductase**. Galactitol is osmotically active and accumulates in the lens, leading to cataract formation. Unlike classic galactosemia (GALT deficiency), galactokinase deficiency is relatively mild and typically presents with isolated cataracts and the presence of reducing substances in the urine (galactosuria).

Flashcard 840: 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.