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Lead Poisoning

Old test problems 96-F, #13 95-F, #7 94-F, #49. 1 o problem: Blockage of enzymes in Heme Synthesis ALA Dehydrase Ferrochetalase. ALA Dehydrase. What functional group does Pb bind to?. d -ALA. porphobilinogen. Pb. Ferrochetalase. Protoporphyrin IX.

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Lead Poisoning

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  1. Old test problems • 96-F, #13 • 95-F, #7 • 94-F, #49 • 1o problem: Blockage of enzymes in Heme Synthesis • ALA Dehydrase • Ferrochetalase ALA Dehydrase What functional group does Pb bind to? d-ALA porphobilinogen Pb Ferrochetalase Protoporphyrin IX What ion is placed on protoporphyrin IX in Pb poisoning? Heme Lead Poisoning • Heme • RBCs • Coproporphyrin III • d-ALA • Treatment: EDTA-Ca++

  2. Old test problems • 96-F, #46 • 95-F, #45 • 95-F, #46 Phenylketonuria 1o problem: Phenylalanine hydroxylase deficency Phenylalanine hydroxylase Tyrosine Phenylalanine These steps are not normally used except when Phe builds up Phenyllactate Phenylacetate Phenylpyruvate Adrenaline Thyroxine Melanin • Phenylalanine, phenyllactate, phenylacetate, phenylpyruvate • Tyrosine, Adrenalin, Thyroxine, Melanin • Retardation, failure to grow, microcephaly • Pigmentation (melanin) • Tyrosine becomes an essential amino acid • Low Phe diet, but not a Phe deficient diet

  3. Old test problems • 96-F, #36 • 95-F, #6 Diabetic Ketoacidosis Build up of ketone bodies in type I diabetics (insulin deficient) Blood Sk. Muscle/ adipose • Without insulin, SKM/AD cannot uptake Glc • SKM/AD respond as if the body is starving • Gluconeogenesis and lipolysis are triggered • GNG exacerbates the high Glc • Lipolysis leads to an increase in ketone body formation Insulin R. Insulin + GLUT4 Glc Glc • HCO3- • pH • Blood glucose • Ketone bodies • Urea (Why?) • Insulin • Glucagon/Glucocorticoids • b-oxidation • Gluconeogenesis

  4. Old test problems • 96-F, #52 Homocystinuria 1o deficiency: Cystathionine synthetase Cystathionine synthetase Serine Homocysteine Cystathionine Proprionyl CoA Cystine S-adenosylhomocysteine • Methionine, S-AdMethionine, S-AdHomocystine, Homocystine • Cystine • Mental retardation • Dislocation of the lens S-adenosylmethionine Methionine

  5. Old test problems • 96-F, #20 Hyperammonemia 1o deficiency: urea cycle enzymes or liver damage Mitochondria Cytosol Aspartate NH4 + CO2 Citrulline Citrulline Argininosuccinate Deficiency at any step can cause hyperammonemia Carbamoyl Phosphate Fumarate Arginine What other pathway uses this compound? Ornithine UREA Ornithine • Can be acquired by alcoholism, hepatitis, bile duct obstruction • Can be inherited: deficiencies in five urea cycle enzymes have been noted • NH4+ • Glutamine • Pyrymidine biosynthesis • Transaminase levels • Hepatomegaly • CNS problems (listlessness, poor vision, screaming) • Coma

  6. Old test problems • 96-F, #34 • 95-F, #8 • 94-F, 41 O N N O COOH Orotic Aciduria 1o deficiency: Enzymes in pyrimidine biosynthesis Orotate phosphoribosyl transferase OMP decarboxylase OMP UMP Orotate (orotidylic acid) CO2 • Orotate (forms crystals in urine) • UMP, pyrimidines • Hemoglobin • RBCs • Treatment: uridine supplements O N N O What are these structures?

  7. Old test problems • 96-F, #14 • 95-F, #5 • 94-F, #37 Insulinoma 1o problem: Benign tumor of pancreatic islet cells. Insulin release from tumor is not regulated (haphazard) B B B SH SH S S S S C C SH SH S S S S A A A Insulin Proinsulin Pre-Proinsulin C Peptide C Note: Not exactly how peptides line up, see Figure 69 of the paper • Glucose tolerance test shows mild diabetes • Blood sugar in fasting state (rises or falls?) • Blood sugar after a meal (rises or falls?) • NORMAL- Endogenous insulin levels should reduce when treated with exogenous insulin. (insulin challenge test) • INSULINOMA- Endogenous insulin levels (measured by peptide C levels) do not fall after exogenous insulin is added.

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