Metabolism — Flashcards

Flashcard 811: 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 812: 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 813: 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 814: 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 815: 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 816: 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 817: 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.

Flashcard 818: A study is being performed that includes certain men -Further analysis shows that these men have an X-linked mutation affecting the phosphoribosyl pyrophosphate (PRPP) synthetase gene. -This lead to increased substrate conversion. -What organ is most likely to develop pathology secondary to this mutation?

Answer: Joints due to Gout, PRPP leads to high purines and uric acid that leads to gout.

Flashcard 819: What are the followings in relation to gluconeogenesis? -Glycogen phosphorylase -Hormone sensitive lipase -Lipoprotein lipase

Answer: Glycogen phosphorylase: involved in the break down of glycogen. It is the rate-limiting enzyme in glycogenolysis. Occurs during 1st several hours of fasting. 2 days will most likely be gluconeogenesis. -Hormone sensitive lipase: enzyme found in adipose tissue, will break down tryglycerides into glycerol & free fatty acids--------> leads to glucose & ketone bodies. It depends on stress hormone (catecholamines, glucagon, ACTH) -Lipoprotein lipase: enyzme found in bloodstream will break down tryglycerides found chylomicrons & VLDL and turn them to free fatty acids acids. very similar to hormone sensitive lipase.

Flashcard 820: A 5-day-old newborn presents with emesis, jaundice, lethargy, and hepatomegaly. Labs show hypoglycemia and elevated transaminases. Blood culture is positive for Gram-negative rods. Which metabolic enzyme is most likely deficient?

Answer: Galactose-1-phosphate uridyltransferase (GALT) :: Classic galactosemia; typically presents with vomiting, jaundice, hepatomegaly, cataracts, and E. coli sepsis.