EVERYTHING YOU NEED TO KNOW FOR METABOLISM 2 FINAL EXAM (new stuff) “IF IT’S NOT ON HERE IT’S NOT ON THE TEST” – our TA Includes: review slides (NOT posted on Bb) as well as personal notes and tips Water Soluble Vitamins Vitamin C and B vitamins o Required in small amounts o Not stored in body in large amounts o Excreted easily in urine to maintain balance o Only toxic in mega-doses o Most involved in energy metabolism oShe loves this chart. So memorize it! Tips for the final: • Our professor LOVES bones. She does research and stuff on them. So definitely read up on calcium, vitamin d, and osteoporosis information • Know what grains are typically enriched with : Thiamin, Folate, Iron, and Niacin. • Our professor’s daughter had hyperbilirubinemia – it’s discussed in the review slides, so she will probably ask a question regarding that • Know all of the conversion amounts such as the amount of niacin that can be made from tryptophan/protein etc..Vitamin B2 – Riboflavin ●Part of 2 co-enzymes involved in electron transport ○FMN- flavin mononucleotide. ○FAD- flavin adenine dinucleotide ●Tri-cyclic molecule which is easily phosphorylated to form FMN and FAD. ●Mg2+ or Mn2+ is used along with ATP to convert riboflavin to FMN ●Mg2+ or Mn2+ along with ATP and FAD synthetase are used to convert FMN to FAD Digestion and Absorption ●Protein parts are removed by stomach acid and enzymatic hydrolysis ●FAD and FMN release their riboflavin part so that it can be absorbed. ●The free riboflavin is then absorbed via active transport (~95%) ●It is phosphorylated again in the liver. ●Predominant form in tissue is FAD Sources: ●Milk/Dary, grain products (enriched), meats ○NADPH is measured, then FAD is added to re-measure and determine “Activity Factor”Vitamin B3 – Niacin ●Generic name for nicotinic acid/ nicotinamide ●Goes through redox reactions NAD -> NADH Sources: ●Meat and fish – BEST ○Provide niacin as free nicotinamide ○NAD and NADP undergo hydrolysis <- both can be absorbed ●Other sources are cereals, legumes, seeds, coffee, tea●Corn- poor source! ○Low in tryptophan. Niacin is unavailable unless treated with lime water. ●NAD can also be synthesized in liver from tryptophan (3%) ○60 mg dietary tryptophan = 1 mg niacin equivalent Functions: ●~200 enzymes, mostly dehydrogenases ●NAD- Oxidative rxn’s ○Glycolysis, acetate oxidation in Krebs, Beta-Oxidation ●NADH- electron transport from metabolic intermediates ○Produces ATP in ETC ●NADP- hexose monophosphate shunt and malate shuttle ●NADPH- reducing agent ○In FA synth, cholesterol synth, DNA precursor synth. DRI ●14 NE/day or 7-7 NE per 1000 kcal ●1 NE = 1mg Niacin = 60 mg tryptophan = 6000 mg protein Deficiency: ●THE 4 D’S ●Dermatitis – like sunburn ●Diarrhea- nausea, vomiting, diarrhea or constipation ●Dementia- neurological such as headache, apathy, memory loss, paralysis, delirium ●Death – if untreated Population at risk: ●People with higher energy requirements ●Drug interference – Isonizid (for TB) ●Genetic disorders where some amino acids can’t be absorbed such as tryptophan ○Hartnup disease ■Autosomal recessive metabolic disorder can’t absorb tryptophan. Nicotinic acid improves cholesterol by lowering LDL and VLDL while increasing HDL It releases histamine (flushing), can also cause skin and GI problems Also used to treat some mental disorders? (questionable now) Assessment of nurtriture:■Measurment of N’ methyl nicotinamide in urine after a 50 mg test dose. ■Urinary excretion of N’methyl nicotinamide ○>5 mg/g creatinine = deficient ○.5 – 1.59 mg/g creatinine = marginal ○1.6 mg/g creatinine = adequateFolate (folic acid) ■Multiple residues composed of pteridine, PABA, and glutamic acid ○All components must be present ○All components can be synth. By body except coupline of pteridine with PABA ■Polyglutamate forms of folate need to be hydrolyzed to monoglutamate in digestion to be absorbed ○Catalyzed by gamma-glutamylcarboxypeptidases or conjugases ■Zn dependent. Zn deficiency may inhibit folate absorption ■Foods containing conjugase inhibitors: legumes, lentils, oranges, cabbage ■Within intestinal cells, folate is reduced to active forms ○Tetrahydrofolic acid (THF) ○Dihydrofolic acid (DHF) ■Folate receptors found in several tissues ■Total body folate is 11-28 mg, half is in liver (THF) ■Functions: ○THF serves to transfer 1 carbon groups ○In synthesis of purines/pyrimidines (DNA, RNA) ○In metabolism of AA’s (glycine-serine synth, methionine regeneration, histidine) ■Sources: ○Green leafy veggies, fruits, legumes, organ meats and yeast ■Raw foods, higher in folate ■Easily destroyed by heating and processing ■Bioavailability varies ■DRI: ○Dietary Folate Equivilents (DFE) ○DFE = microgram food folate + (1.7 *ug synthetic folate) ■Synthetic folate has more bioavailability ■Deficiency Risk: ○Poor diet ■Destroyed with freezing, processing, prolonged storage ○Intestinal malabsorption ■Alcoholics, celiacs disease○Inadequate metabolism ■Drug interactions ●Methotrexate (Chemo) ●Some antimicrobials ●Anticonvulsants (Dilantin) ○Those with increased demands ■Pregnancy/Lactation ○B12 deficiency ■Folate Deficiency: ○Megaloblastic, macrocytic anemia ■Large, immature erythrocytes ○Neural tube defects (spina bifida, anencephaly) ○Possibly in beginning stage of cancer ■Status assessment: ○RBC folate levels ■(160-800 ng/mL) show long-term status ○Plasma folate ■(methyltetrahydrofolte, 6-25 ng/mL) shows short term status ○RBC and serum folate will depend on B12 ■Methyl folate trapVitamin B12 – Cobalamin Known as corrinoids- corrin structure o 4 pyrrole rings attached together with Cobalt in center o Other groups can attach to Co to form: 5’-deoxyadenosylcobalamin (5’-deoxyadenosyl group) Methylcobalamin (CH3 group) Cyanocobalamin (CN group) Hydroxocobalamin (OH group) Aquocobalamin (H2O) Nitricobalamin (NO2 group) Absorption: o Released from foods by pepsin in stomach o Free cobalamin attaches to R proteins which have high affinity for cobalamin These R proteins move cobalamin from sromach to small intestine R protein is hydrolyzed in duodenum, cobalamin is released Intrinsic Factor (IF) (synthesized in stomach) binds to cobalamin in
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