I. Thiamin A. History: Discovered when Japanese sailors whose diet consisted of polished rice were suffering from neurological disease (later known as Beri Beri). B. Sources: a. Food: meat (especially pork), legumes, whole and enriched brans, breads, and cereals. b. Supplements: thiamine hydrochloride, thiamine monocitrate C. Stability: a. Water soluble (which means it is excreted in the kidneys) b. Denatures in alkaline mediums (i.e. cooking in baking soda) c. Denatures in heat (i.e. overcooking vegetables) D. Digestion/Absorption/Transport/Storage a. Digestion: Thiamin is digested in both its free form and its coenzyme form. Phosphorlyated thiamin is hydrolyzed by phosphatases to form free thiamin so that it can move into the enterocytes. b. Absorption:i. Enterocytes: thiamin can be phosphorylated here into its coenzyme form and transported via active transport. 1. High concentrations: passive diffusion 2. Low concentrations: active transport via sodium dependent channels ii. Brush boarder: thiamin transports across the basolateral membrane via a thiamin/H+ antiport system. Ethanol interferes with this transportation. 1. Anti-absorption factorsa. Thiminases: enzymes found in raw fish that cleave the middle bond of thiamin so that it cannot be absorbed inthe body b. Polyphenols: thermostable organic substance found in coffee, tea, brussel sprouts, blueberries, and red cabbage. Inactivates thiamin by oxyreductive processes,facilitated by Ca2+ and Mg2+. It can be prevented by citric acid or vitamin C. iii. Blood: 1. Red Blood Cells: 90% transported inside RBCs2. Albumin: 10% bound to albumin iv. Tissues: once distributed to the tissues, thiamin can be phosphorylated to its coenzyme form so that it can be used by the cells. 1. Thiamin(thiamin pyrophosphokinase) TPP 2. TPP(TDP-ATP phosphoryl transferase)TTP E. Coenzyme Roles a. Pyruvate dehydrogenase complex (also uses B5, Niacin, Riboflavin)b. α-Ketoglutarate dehydrogenase complex (also uses B5 and Niacin) c. Branched chain ketoacid dehydrogenase d. HMP shunt: transketolase (produces NADPH and cholosterol for FA synth)e. Synaptic function: TPP released by synaptic cleft after action potential reaches (think about biochem- mad hatter’s disease) F. Assessment: a. Urinary b. Blood G. Deficiency a. Beri Beri i. Wet: enlarged heart, edema ii. Dry: anorexia, nausea, neurological damage, vomiting iii. Infant: result of deficiency of mother during breast feeding. Causes heart failure, syanosis, dyspenia, and aphonia b. Wernicke’s Encephalopathy: often seen with alcoholics; causes neurological symptoms like atoxia and delirium i. Associated with Korsakoff’s psychosis 1. Chronic alcoholism, polyneuritis, inability to acquire new information, confabulation c. Prevention: avoid polished grains, cooking too much or in alkali solutions (denatures), anti-absorption foods, avoid high carbohydrate intake II. Riboflavin A. Sources: enriched breads and cereals, legumes, green vegetables, dairy products, meat, eggs B. Forms: FAD, FMN, riboflavin C. Digestion: a. Mouth: eaten in all forms b. Stomach: proteases and HCl degrade coenzyme forms to free vitamin form so that it can be absorbed by the enterocytes D. Absorption: normal a. Blood: transported by proteins (most commonly albumin) b. Tissues: converted into coenzyme form so it can be used by the cells E. Coenzyme Functions a. FADi. Pyruvate dehydrogenase (B5, niacin, riboflavin, thiamin) ii. Succinate (succinate dehydrogenase) fumarate iii. α-Ketoglutarate succinyl CoA (α-ketoglutarate dehydrogenase complex- also uses B5, TPP, and Niacin) iv. Fatty Acyl CoA(fatty acyl CoA dehydrogenase) Enoyl CoAv. Needed for folate, B6, and GSSG (antioxidant function) vi. Neurotransmitter function (monoamine oxidase) vii. Needed for the synthesis of niacin from tryptophan viii. Drops off electrons to the ETC in the form of hydrogens to produce 2ATP b. FMN i. Found in the ETC cycle in complex I F. Assessment:a. Erythrocyte glutathione reductase b. Urine G. Deficiency:a. Ariboflavinosis b. Fatigue, weakness, anemia, glossitis, peripheral nerve function, dermatitis, chleiosis, stomatitis H. Those at risk: heart disease, alcoholics, cancers, thyroid disease, diabetes III. Niacin A. Sources: fish, enriched cereals and breads, meats (mostly animal products) B. Forms: NAD, NADP, niacin C. Digestion: a. Mouth: eaten in all forms b. Stomach: proteases and HCl degrade coenzyme to free vitamin form so that it can be absorbed by the enterocytes D. Absorption normal E. Coenzyme functions: a. NAD i. Glycolysis: glyceraldehyde-3-phosphate (glyceraldehyde-3-phosphate dehydrogenase) 1,3-bisphosphoglycerate ii. Intermediate: pyruvate dehydrogenase (thiamin, riboflavin, and B5) iii. Krebs: 1. α-Ketoglutarate succinyl CoA (α-ketoglutarate dehydrogenase complex- also uses B5, TPP, and Riboflavin) 2. isocitrate (isocitrate dehydrogenase) α-ketoglutarate 3. Malate (malate dehydrogenase) OAA iv. Beta oxidation 1. β-hydroxyl acyl CoA dehdyrogenase v. oxidation of ethanol1. alcohol dehydrogenase and acetaldehyde dehydrogenase vi. found in the ETC (NADH dehydrogenase complex I) vii. DNA: NAD donates adenosine diphosphate ribose and attaches it to a cyclic ADP ribose b. NADP i. HMP shunt ii. FA synthesis and cholesterol synthesis iii. Folate metabolism iv. Alcohol metabolism (MEOS) F. Assessment: normal G. Deficiencya. Pellagrai. Dementia ii. Dermatitis iii. Death iv. Diarrhea H. Those at risk a. Alcoholics, malabsorptive disorders, medications (isolazid), Hartnup’s Disease I. Toxicity a. High pharmacological doses (nicotinic acid, niacor, advicor)i. Vasodilation causing flushing, itching, and headaches ii. Glucose intoleranceiii. GI discomfort, heart burn, nausea iv. Hepatic toxicity, liver failure, jaundice IV. Pentathenic Acid (B5) A. Sources: everywhere B. Forms: Pentothenoate, pentothenol C. Digestion: a. Mouth: eaten in all forms. 85% of the time its ingested as coenzyme A which can then form pantothenic acid D. Absorption: a. Intestine: i. High concentrations: passive diffusion ii. Low concentrations: multivitamin carrier (biotin) b. Portal blood i. Extracellular (free in plasma) ii. Intracellular (RBC) c. Tissues: inside the cell pantothenic acid is converted to CoA i. Pantothenate 4-phosphopantothenate pantethiene CoA E. Coenzyme Functions a. Thioester formation in various metabolic reactions i. Intermediate: 1. Pyruvate + CoA Acetyl
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