Metabolism — Flashcards

Flashcard 811: 78 y/o woman presents with tenderness and easy bleeding of the gums when brushing her teeth. - Physical exam: swollen gingiva that bleed on probing. - Skin: perifollicular hemorrhages and petechiae are noted. Her symptoms are most likely caused by hypoactivity of an enzyme found in which cellular compartment?

Answer: Rough endoplasmic reticulum (RER) This is where Vitamin C-dependent hydroxylation of proline and lysine residues (on procollagen chains) occurs. Deficiency leads to scurvy.

Flashcard 812: A researcher is investigating the relationship between insulin concentration and the number of glucose transporters on the cell surface. - **Circles**: Surface transporter count increases as insulin concentration rises. - **Triangles**: Surface transporter count remains constant regardless of insulin concentration. Which cell types are most likely represented by the circles and triangles?

Answer: **Circles**: Skeletal muscle or Adipocytes (Insulin-dependent; uses **GLUT4**) **Triangles**: Most other cells (Insulin-independent; e.g., Liver, Brain, RBCs, Kidney)

Extra: Insulin-dependent glucose uptake occurs in skeletal muscle and adipose tissue via **GLUT4**. In the absence of insulin, GLUT4 is sequestered in intracellular vesicles. Insulin signaling triggers the translocation of these vesicles to the plasma membrane. Most other tissues (Liver, RBCs, Brain, Kidney) use insulin-independent transporters (GLUT1, 2, 3, or 5) which are constitutively present on the cell surface.

Flashcard 813: A researcher develops an agent that specifically blocks the interaction of inositol triphosphate (IP3) with its intracellular receptor. Compared to control cells, decreased activity of which enzyme is most likely to be observed in the experimental cells?

Answer: Protein Kinase C (PKC) IP3 binds to receptors on the smooth endoplasmic reticulum to release intracellular calcium (Ca2+). Both Ca2+ and DAG are required to activate Protein Kinase C.

Flashcard 814: A newborn presents with lethargy, vomiting, and hypotonia during the first few days of life. - Lab: metabolic acidosis with large anion gap, ketosis, & hypoglycemia. - Concentration of propionic acid is increased in the plasma and urine. - Metabolism of which amino acids contributes to this patient's condition?

Answer: Valine, Isoleucine, Methionine, and Threonine (Mnemonic: VOMIT — Valine, Odd-chain fatty acids, Methionine, Isoleucine, Threonine) This patient has Propionic Acidemia, caused by a deficiency of propionyl-CoA carboxylase (requires Biotin/B7 as a cofactor). This enzyme normally converts propionyl-CoA to methylmalonyl-CoA. Accumulation of propionic acid leads to metabolic acidosis, ketosis, and hypoglycemia.

Flashcard 815: In which diseases would a deficiency of these enzymes present? - Acid α-glucosidase - Aldolase B - Fructokinase - Galactose-1-phosphate uridyl transferase - Lactase

Answer: - **Acid α-glucosidase**: Pompe disease (GSD type II) - **Aldolase B**: Hereditary fructose intolerance - **Fructokinase**: Essential fructosuria - **Galactose-1-phosphate uridyl transferase**: Classic galactosemia - **Lactase**: Lactose intolerance

Extra: - **Pompe disease**: Lysosomal acid maltase deficiency. Characterized by cardiomegaly, hypertrophic cardiomyopathy, exercise intolerance, and systemic findings leading to early death. - **Hereditary fructose intolerance**: Deficiency of Aldolase B leads to accumulation of fructose-1-phosphate; presents with hypoglycemia, jaundice, and cirrhosis after ingestion of fructose, sucrose, or sorbitol. - **Essential fructosuria**: Deficiency of fructokinase; a benign, asymptomatic condition where fructose appears in blood and urine. - **Classic galactosemia**: Deficiency of GALT. Presents with failure to thrive, jaundice, hepatomegaly, infantile cataracts, and intellectual disability. - **Lactose intolerance**: Deficiency of lactase results in osmotic diarrhea, bloating, and flatulence after dairy consumption.

Flashcard 816: What are the following enzymes associated with? - Acetyl CoA carboxylase - Acyl CoA synthetase - ATP citrate lyase - Glucose-6-phosphate dehydrogenase - Glycerol kinase

Answer: - Acetyl CoA carboxylase: Conversion of acetyl-CoA to malonyl-CoA in fatty acid synthesis (Biotin/B7 cofactor). - Acyl CoA synthetase: Activation of fatty acids for breakdown; forms acyl-CoA which then enters mitochondria via the carnitine shuttle. - ATP citrate lyase: Conversion of citrate to acetyl-CoA in the cytosol for fatty acid synthesis. - G6PD: Pentose phosphate pathway; provides NADPH and ribose (nucleotide synthesis). - Glycerol kinase: Phosphorylation of glycerol for conversion into glucose (gluconeogenesis) or triglycerides.

Flashcard 817: In what disease should the followings be restricted? -Galactose -Leucine -Methionine -Phenylalanine -Tyrosine

Answer: Galactose: galactosemia (due to deficiency of Galactose-1-phosphate uridyl transferase) (GALT def.) -Leucine: Maple syrup disease, due to deficiency of branched chain a-ketacid dehydrogenase. -Methionine: should be restricted in homocysteinuria,because methionine converts to homocystein. Instead you will want to give B12 (cobalamine) to convert to methionine & B6 (pyridoxine) to convert to cysteine to relieve the high level of homocysteine. -Phenylalanine: Phenylketonuria (def. of phenyl hydroxylase), musty odor, neurological symptoms. -Tyrosine: restricted in hypertyrosinemia (progressive liver & renal disease) or in alkaptonuria (homogentisate oxidase def.) (black urine on air, black cartillage).

Flashcard 818: 31 y/o patient presents with myalgias, anorexia, & skin rash. -He doesn't do drugs or alcohol. -He has been consuming large amounts of raw egg whites for the past several months. -Physical exam: macular dermatitis of the extremities. -A water-soluble vitamin deficiency is suspected as the cause of his condition. -Which biochemical conversion(s) most likely use the deficient vitamin as a cofactor?

Answer: Pyruvate to oxaloacetate (and other carboxylation reactions) The patient has Biotin (Vitamin B7) deficiency due to excessive consumption of raw egg whites (avidin binds biotin, preventing absorption). Biotin is a cofactor for carboxylase enzymes: 1. Pyruvate carboxylase (Pyruvate → oxaloacetate) 2. Acetyl-CoA carboxylase (Acetyl-CoA → malonyl-CoA) 3. Propionyl-CoA carboxylase (Propionyl-CoA → methylmalonyl-CoA) Deficiency leads to dermatitis, alopecia, myalgias, and lactic acidosis (due to pyruvate being shunted to lactate).

Flashcard 819: A 2 y/o boy is being evaluated for failure to thrive and developmental delay. - Past Medical history: recurrent ear infection since age 6 months. - Physical Exam: coarse facial features, corneal clouding, hepatosplenomegaly and restricted joint mobility. - Mass spectrometry analysis: Deficient phosphorylation of mannose residues on certain glycoproteins in the Golgi apparatus. - Normally, these proteins are most likely to be transported to which cellular location?

Answer: Lysosome This describes **I-cell disease** (inclusion cell disease), which is a defect in protein targeting due to the lack of phosphorylation of mannose residues (**mannose-6-phosphate** tag). Without this tag, lysosomal enzymes are secreted extracellularly rather than being delivered to lysosomes, leading to an accumulation of cellular debris (inclusion bodies).

Flashcard 820: What are the following substances associated with in relation to cofactors or chemical reactions? - Biotin - Folic acid - Niacin - Pyridoxine - Riboflavin - Thiamine

Answer: - Biotin (B7): Cofactor for carboxylase enzymes (e.g., Pyruvate carboxylase). - Folic Acid (B9): Cofactor for nucleic acid synthesis (1-carbon transfer). Deficiency leads to megaloblastic anemia. - Niacin (B3): Cofactor for redox reactions (NAD+/NADP+). Deficiency leads to Pellagra (Dermatitis, Diarrhea, Dementia). - Pyridoxine (B6): Cofactor for transamination (e.g., ALT, AST) and decarboxylation. - Riboflavin (B2): Cofactor for redox reactions (FAD, FMN). - Thiamine (B1): Cofactor for α-ketoacid dehydrogenases (Pyruvate DH, α-ketoglutarate DH, Branched-chain α-ketoacid DH) and Transketolase.