Pyridoxine B6 Sources o Foods Animal products beef salmon light meat chicken Whole grain products bananas nuts o Supplements pyridoxine hydrochloride o Bioavailability B6 is lost through Prolonged heating canning milling freezing sterilization sanitizing Forms 6 vitamers o 3 forms alcohol aldehyde amine Absorption o Eaten in all 6 forms o Intestine Brushborder phosphorylated forms are dephosphorylated Jejunum PNP PLP PMP PN PL PM Passive diffusion we absorb 75 of B6 eaten Enterocyte released into portal blood o Tissues Liver Stores 5 10 of vitamin Site of metabolism of vitamin Plus in liver pyridosal phosphate stored in Extra released to blood in pyridsal form to liver or leaves liver be excreted Stores 75 85 of vitamin Stored as PLP bound to glycogen phosphase makes it stable and unstable to diffuse from cell Muscle Function PLP o 100 enzymes most involved in aa metabolism use o Coenzyme roles coenzyme roles noncoenzyme roles Transamination of pyriodoxal phosphate PLP Decarboxylation removal of amino group formation of non essential amino acids neurotransmitter synthesis glutamate GABA Cleavage L Dopa dopamine dopa made from tyrosine Serine Glycine Cleaves hydroxymethyl group off of serine to tetrahydroxfolate THF and forms glycine Enzyme serine hydroxymethyl transferase requires PLP Methione Cysteine Enzymes cystathionine synthase and cystathione lyase require PLP Synthesis of porphyrins Other PLP coenzyme for aminolevulinic acid synthase ALA synthase PLP synthesis of niacin from tryptophan Tryptophan PLP niacin Glycogen to glucose 1 phosphate Assessment Urine o Excreted in urine as 4 pyridoxic acid o Indicative of intake not stores Plasma PLP most reliable RNC amino transferase activities Indirect test o Tryptophan load test urinary xanthurenic acid o Methione load test urinary cystathionine RDA Deficiency Males females 1 3 mg d UL 100 mg d Rare 1950s processing of infant milk symptoms convulsions size but are pale in color impaired heme synthesis o adults sleepiness fatigue cheliosis glossitis stomatitis o infants neurological problems abnormal EKG seizures o Hypochromic Microcytic Anemia blood cells are same o Altered calcium magnesium metabolism o Hyperhomocysterinemia o Impaired niacin synthesis o Elderly poor intake and increase hydrolysis of PLP o Excess alcohol impair conversion of PV PM to PLP and o Long term dialysis o Medications isoniazid penicillamine corticosteroids risk factor fro heart disease increase hydrolysis of PLP anticonvulsants At risk populations Toxicity Peripheral and sensory neuropathy o Symptoms include unsteadily gait paresthesia tingling numbness of toes lower exremeties Demyelination and degeneration of sensory fibers o Degeneration of dorsal root ganglia o UL 100mg d Beneficial effects Commercial claims o Helps with carpal tunnel syndrome PMS depression muscular fatigue autism hyperhomocysteinemia Must stay under 100mg d Folate supplements Folic acid oxidized form found in fortified foods with Folate reduced form found naturally in foods tissues Sources o Foods Mushrooms green veggies peanuts legumes cituris fruits fortified cereals breads grains structure nutrtional properties to folate o Folacin term used to describe compounds with similar o Bioavailability about 50 on form of vitamin Can be lost in cooking but amount lost depends 96 bioavailable in cooked lima beans 25 in romaine lettuce Structure o We can make all three pieces of the structure in our body however we cannot link them together o Forms Coenzyme forms Additional glutamate residue attached to o Polyglutamates glutamate o Monoglutamate o Biologically active is tetrahydrofolate THF Transport form Digestion and Absorption Eaten as polyglutamate in food Conjugases enzyme o Cleaves polyglutamates dependent pancreatic juice bile o Found in jejunal mucosa brush borders zinc o Conjugase inhibitors legumes lentils cabbage oranges o Folate binding protein AKA folate carries folate Enterocyte Sodium dependent active transport to allow folate receptors into cell o Most absorption in jejunum Portal circulation Liver 33 of THF 5 mrthyl THF 5 formyl THF or 10 formyl THF goes to liver Systemic blood plasma transported as monoglutamate Tissues o Enter cells via folate receptors or folate binding proteins o Converted to polyglutamate forms and trapped Polyglutamate cant move its trapped but monoglutamate can move o 1 3 of folate in liver Functions Mechanism of Action o Accepts 1 C group from metabolic reactions at specific o Donates the 1 C for synthesis reaction including positions N5 and or N10 synthesis of purine and pyrinidine Amino Acid Metabolism o Histidine glutamate o Glycine serine requires PLP o Glycine CO2 and NH4 requires folate and niacin o Homocysteine methione Requires folate o if we don t have enough MET homocysteine will convert itself to MET folate more specifically THF we need a methyl donor first which is found in we get THF when glycine is converted to serine 5 methyl THF binds with cobalamin to make methylcobalamin o Methyl Folate Trap B12 removes methyl group from 5 methyl THF if there is no B12 the mthyl group becomes TRAPPED Purine and Pyrimidine Synthesis o Purines are composed of adenine and guanine o Pyrmidines uridine cytosine and thymine o Folate is essential for cell division o Methotrexate binds to enzymes to prevent cell division This is medication that prevents cell differentiation in cancer cells Urine Used in bile but most of the folate in bile is reabsorbed Excretion Assessment Serum and plasma levels reflect recent dietary intake N forminioglutamate FIGLU excretion o RBC is more indicative of tissues status o Tells folate status at the time RBC was synthesized o Intermediate of histidine glutamate o B12 defieciency also causes an increase in FIGLU excretion Deoxyuridine suppression test Plasma homocysteine functional marker B12 deficiency will also increase homocysteine RDA Males 400 g d Females 400 g d Prenatal 600 g d Deficiency Megaloblastic macrocytic anemia o Clinical low plasma folate o 3 4 months low folate intake RBC folate decrease o 4 5 months bone marrow and other rapidly dividing o blood cells are larger and fewer in number cells become megaloblastic abnormal DNA snthesis large immature cells with lots of hemoglobin o at risk populations malabsorption diseases medications phentoin methotrexate Neural Tube Defects o A malformation of any part of the body along the neural o Happens when pregnant mother has deficiency line Spina bifida Anencepathy
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