HNF 462 1st EditionLecture 5Outline of Last Lecture I. Discovery II. Sources and StructureIII. Digestion, Absorption, and TransportIV. ExcretionV. Functionsa. Electron Transport Chainb. Glutathione ReductaseVI. MeasurementVII. Deficiency and Toxicity a. Activity CoefficientsOutline of Current Lecture I. Discoverya. PellagraII. Sources and Structuresa. Tryptophan and the LiverIII. Digestion, Absorption, and TransportationIV. In the CellsV. Degradation/ExcretionVI. Coenzyme FunctionsVII. Toxicity and Measurementa. RDACurrent Lecture: Vitamin B3 (Niacin)1. Discovery: In the process of trying to find a cure to pellagraa. Pellagra: deficiency diseasei. Symptoms: Dermatitis (looks like sunburn), diarrhea, dementia, and deathii. Associated with a corn-based diet2. Sources and Structurea. Sources mostly are animal-based products and whole grains. Small amount of niacin can be produced in the liver.i. Synthesis in liver by metabolism of tryptophan. 60 mg tryptophan will produce 1 mg niacin (low conversion rate)ii. Reaction starts with tryptophan; ends with nicotinamide; and requires iron, riboflavin, and B6These 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.b. Two Formsi. Nicotinic Acid: OH group attached to niacin ringii. Nicotinamide: NH2 group attached to niacin ring1. Coenzymes to nicotinamide are NAD and NADP3. Digestion, Absorption, and Transportationa. Digestion: required for absorptioni. NADP NAD with help from enzyme pyrophosphataseii. NADNicotinamide with help from enzyme glycohydrolaseb. Absorption: Nicotinamide and nicotinic acid are absorbed (poorly absorbed whenbonded to a complex carbohydrate or small peptide)i. Diffusion in high levelsii. Active transport by Na-dependent transporters in low levelsc. Transportation: in blood mainly in the form of nicotinamide4. In the Cells: transported into cells mainly by diffusiona. Nicotinamide/nicotinic acidNADNADP (phosphorylated by NAD Kinase)b. NAD and NADP are then trapped inside the cell5. Degradation and Excretiona. NAD degraded, methylated/oxidized, and then excreted in urine6. Coenzyme Functionsa. NAD: used in energy metabolism pathwaysb. NADP: used in more diverse pathways (synthesizing molecules, regeneration of antioxidants, and folate metabolism)c. NADNADH: two pathways takeni. NAD can take on 2 electrons and 2 Hs to become NADH (will carry electrons to electron transport chain)ii. NAD oxidizes another molecule to become NADH7. Toxicity and Measurementa. High doses of niacin are used to treat high cholesterol and triglycerides in the blood, but does have side effects (most common is niacin flush)b. Measured by urinary excretion, red blood cell NAD concentration, and plasma 2-pyridone levelsi. RDA for men/women = 16/14 mg per day (increases with pregnancy and
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