HNF 462 1st Edition Lecture 9Outline of Last LectureI. StructureII. SourcesIII. DigestionIV. AbsorptionV. Transport and StorageVI. BioavailabilityVII. ExcretionVIII. Conversions and Functionsa. DNA synthesisb. Homocysteine conversionc. Metabolism of Amino acidsIX. Importancea. Dividing Cellsb. Hyperhomocystenemiac. Neural Tube DefectsX. MeasurementOutline of Current LectureI. Structure and Food SourcesII. Digestion and AbsorptionIII. TransportIV. Storage and ExcretionV. FunctionsVI. DeficiencyVII. Schilling TestThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.Current Lecture: Vitamin B12 (Cobalamin) 1. Structure and Food Sourcesa. Structurei. Cobalt in the center of a corrin ringii. Nucleotide attached to ringiii. R group attached to ring: biologically active only if R group is a methyl group or a deoxyadenosyl groupb. Sources: from animal products only2. Digestion and Absorptiona. Digestion:i. B12 released from protein in stomach and binds to R protein travels to the small intestineii. R protein is digested and frees B12, then B12 binds to an intrinsic factor (IF) travels to ileumiii. Binds to IF receptorb. Absorptioni. Intestinal: IF receptor mediated endocytosisii. Cellular: TC receptor mediated endocytosis. Once in cells, B12 is released from the receptor complex and binds to transcobalamin II to travel to the bloodiii. Inhibitors: lack of IF, old age, and acidic environment in the small intestine3. Transporta. In blood, transported in methyl form (80%) and adenosyl form (20%)4. Storage and Excretiona. Storage: high storage potentiali. 50% stored in the liver5. Functions: Conenzyme in 2 reactionsa. Oxidation of fatty acids and amino acidsi. Methylmalonyl CoA Succinyl CoA uses mutase that is B12-dependentb. Homocysteine Metabolismi. Homocysteine Methionine 5-Adenosyl Methionine (SAM)1. SAM is an important methyl donor in many reactions6. Deficiencya. Increased amount of methylmalonic acid in urineb. Megaloblastic Macrocytic Anemiac. Hyperhomocysteinemiad. Neurological Problemse. High doses of folate can mask B12 deficiency symptomsPatient Condition Methylmalonic Acid HomocysteineHealthy Normal NormalB12 Deficiency Elevated ElevatedFolate Deficiency Normal Elevated7. Schilling Test: Test for efficiency of B12 Absorptiona. Patient given dose of radioactive B12 by mouthb. Large dose of B12 by injection: prevents binding of radioactive B12 to peripheral cellsc. Collect urine: If radioactive B12 is absorbed, it will show up in the urine because the tissues are saturated by the high dose injectiond. If B12 is not absorbed, then doctors will give an oral dose of IF. If absorption improves, the patient has an IF deficiency
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