HNF 462Exam # 1 Study Guide Lectures: 1 - 10 For each vitamin, know the function(s) and the mechanism of their function—this is most important to know! Also know absorption and transport, what affects absorption/bioavailability, the form for transport; interaction with other nutrients; health benefits and well-known diseases from deficiency; storage and excretion, especially when it is about nutrient status assessment or disease related; how nutrient status/absorption is assessed.Lectures 1 & 2 (August 30 and September 4)Vitamin C:1. Functions: - Synthesis Reactions: General Mechanism— vitamin C functions as a reducing agent to maintain the iron/copper atoms in the reduced state- Collagen Synthesis (without proper synthesis, causes hemorrhagic signs)1. Hydroxylation reactions require vitamin C, which converts oxidized iron to its reduced state: hydroxylation important because forms hydrogen bonds between the collagen strands- Carnitine Synthesis (carnitine transports long-chain fatty acids into mitochondrial matrix)1. Last step is a hydroxylation reaction that requires Vitamin C, which maintains the iron in the reduced state- Tyrosine Synthesis and Catabolism1. Last step requires vitamin C to convert oxidized copper and iron atomsto their reduced states- Neurotransmitter Synthesis1. Ascorbic Acid acts as a reducing agent in a hydroxylase reaction- Antioxidant:- Regenerates other antioxidants- Reduces free radicals by donating electrons 2. Absorption:- Digestion not required for absorption into small intestine- Ascorbic acid (AA) and Dehydroascorbic acid (DHAA) are both absorbed throughout small intestine- Efficiency decreases with increased Vitamin C intake (unabsorbed vitamin C is metabolized by intestinal flora)- SVCTs are inhibited by high intracellular glucose concentrations3. Transport:- Intestinal Cells:- AA is transported into cells by Na-dependent SVCT1 and SVCT2- DHAA is transported into cells by facilitated diffusion with GLUT 1 & 3- Peripheral Cells:- AA transported by SVCT1 and SVCT2- DHAA absorbed into peripheral cells by GLUT1, 3, and 44. Interaction with Other Nutrients: - AA enhanced intestinal absorption of nonheme iron5. Health Benefits and Deficiency:- Deficiency:- Scurvy: Hemorrhagic signs, hyperkeratosis of hair follicles, hypochondriasis,hematologic abnormalities- Worsens dietary carnitine deficiency - Health Benefits:- Optimizes immune function—prevents common cold- Decreased risk of certain cancers- Prevents LDL oxidation, so macrophages absorb LDL less efficiently decreased risk of cardiovascular disease6. Excretion:- Vitamin C is absorbed by the kidney until kidney is completely saturated- Excess Vitamin C is excreted via urine- Kidney Stones: oxidized form of vitamin C (oxalic acid) is not soluble in water and cancause stones, so it is thought that too much vitamin C may increase chance of stones7. Measuring Nutrient Status:- Blood Concentrations- Physical and chemical methods of measurementLecture 3 (September 6)Vitamin B1/Thiamin:1. Functions:a. Coenzymei. Pyruvate Dehydrogenase Complex- In Pyruvate Decarboxylation reaction: Pyruvate converted to Acetyl-CoA- Vitamin B1 holds acetyl group temporarily from pyruvate and then transfers it to intermediate Lipoamideii. Alpha-Ketoglutarate Dehydrogenase Complex- Alpha-Ketoglutarate Succinyl-CoA- Similar mechanism to pyruvate decarboxylationiii. Transketolase (key enzyme in pentose phosphate pathway)- Vitamin B1 acts as coenzyme to trasketolase for the generation of NADPHiv. Branched-Chain Alpha-Keto Acid Dehydrogenase Complex- Similar mechanism to pyruvate decarboxylation- Thiamin in form of TDP: decarboxylates branched-chain amino acids (leucine, isoleucine, and valine) in order to metabolize them2. Absorption:- Digestion of TDP/TMP needed for absorption—must be in the free form (no phosphate groups)- High intakes by passive diffusion- Low intakes by Na-dependent transporter- Cellular Absorption in free thiamin form of TMP (in liver, phosphorylated to TDP)- High bioavailability- Absorption Inhibitors: thiaminases, tannic/caffeic acids, ethanol3. Transport:- In blood: free form bound to albumin or unbound TMP4. Health Benefits and Deficiency:a. Deficiency:- Beriberi: wet, dry, acute- Loss of appetite, cardiovascular abnormalities, neurological symptoms5. Excretion:- Excreted via urine- In free form, TDP, or TMP6. Measuring Nutrient Status:- Transketolase Activity measured in red blood cells: increase in transketolase = thiamin deficiency- Decrease in creatinine levels = thiamin deficiency Lecture 4 (September 9)Vitamin B2/Riboflavin:1. Functions:- Coenzyme: Oxidizing agent—will accept a pair of hydrogen atomsi. Electron Transport Chain- FADH2 FAD - Coenzyme for complex 1ii. PDHC: uses FADH2iii. Succinate Dehydrogenase: uses FADH2iv. Acyl CoA Dehydrogenase: uses FADH2v. Glutathione Reductase (recycles glutathione): Converts oxidized glutathione (GSSG) to reduced glutathione (GSH)2. Absorption:- FMN/FAD must be digested/dephosphorylated (by FAD pyrophosphatase) in order for free riboflavin to be absorbed- Intestinal Absorption: active transport by Na-independent carriers in low intakes; passive diffusion at high intakes- Cellular Absorption: Free riboflavin via riboflavin-binding proteins (once in cells converted to coenzyme forms- FMN or FAD)- High bioavailability (animal sources better than plant sources): inhibited by divalent metals and ethanol3. Transport:- In blood: mainly as free riboflavin, but other forms present too- Bound to proteins in blood (albumin, fibrinogen, and globulins)4. Interaction with Other Nutrients:- Coenzyme for reactions that include B6, Folate, and Niacin5. Deficiency:- Ariboflavinosis: lesions on lips, tongue/skin inflammation, neuropathy, anemia6. Excretion:- Non-protein bound vitamin B2 is filtered by kidney and excreted via urine- Small amount excreted via feces7. Measuring Nutrient Status:- Measure of glutathione reductase activityo AC = Enzyme Activity + FAD / Enzyme Activity - FADLecture 5 (September 11)Vitamin B3/Niacin1. Functions:a. Coenzyme- NAD: energy metabolism reactions: Glycolysis, pyruvate dehydrogenase complex, acetyl CoA oxidation, oxidation of fatty acids and ethanol- NADP: more diverse pathways: fatty acid/cholesterol/steroid synthesis, regeneration of glutathione/vitamin C/thioredoxin, folate metabolism2.