Exam 2 Cobalamin B12 RDA o Males and females 19 30 is 2 4 micrograms Sources can also be made by bacteria o Foods Animal products Meat Poultry Fish clams and oysters o Very high amounts Eggs Milk No plant products Vegetarians needs supplements Kumbacha Batabuta or fermented teas Forms o Cobalamin Generic term for group of compound is called corrinoids Corrin Nucleus o Macricyclic ring of 4 pyrrole rings o Corrin has Cobalt attached Group CH OH etc attached to the Cobalt is what determines the form of Cobalamin Forms can convert to other forms if needed Review to the slides to see the forms on the chart o CH3 methylcobalamin o 5 deoxyadenosyl adenosylcobalamin o Meat Products o Milk Products Adenosylcobalamin Hydroxocobalamin Methylcobalamin Hydroxocobalamin o Supplements Cyanocobalamin Hydroxocobalamin Digestion and Absorption o Eaten in all forms o Stomach Pepsin and HCL released cobalamins from polypeptide chains R Protein cobalophins hepatocorrins are found in saliva and gastric juices and they bind to B12 Intrinsic factor made and released in the stomach but functions in the small intesting o Small Intestine Cobalamin in released from R Protein by pancreatic proteases Intrinsic factor binds to cobalamin Illeum Pharmacological doses passive diffusion Dietary doses o Cubilins receptor for B12 o B12 IF enter cell by receptor mediated Denterohepatic Circulation endocytossi Bile o Transport Bound to one of the three transcobalamins TC1 Circulating storage form TC2 Carries newly absorbed cobalamin to tissues TC3 Delivery uptake from peripheral tissues to liver o Tissues Uptake at tissues Receptor for TC2 Receptor mediated endocytosis Lysosome degrades TC2 Free B12 inside tissue Storage o Liver main storage site and can be stored for up to 11 years o Lesser amounts stored in muscle kidneys brain bone heart spleen blood as trans cobalamin Enzymatic Reactions o Homocysteine Methionine 2 step process Formation of Methylcobalamin Methylcobalamin donates methyl group to Homocystein form cobalamin and Methionine o Methylmalonyl Succinyl CoA Succinyl CoA is a krebb cycle intermediate Propionyl CoA Methylmalonyl CoA 5 deoxyadenosylcobalamine Uses Biotin B6 Methylmalonyl CoA Succinyl CoA Adenosylcobalamin B12 OR Methylmalonyl CoA Methylonoic Acid No B12 present deficient Excretion o Urine very little o Bile enterohepatic circulation Most bile is sent to the liver to be reused o Can be stored for 11 years so usually rate to see until a long time after Assessment Main tests o Serum B12 Not the best way Serum levels can be falsely high or low with conditions or other diseases o Methylmalonic acid Increased with B12 deficiency Serum or Urinary o Homocysteine Increased with B12 deficiency and other factors o Deoxyuridine Supression Test DUST Impaired thymidine synthesis due to lack of B12 Complicated and expensive Also seen in Folate tests o TC2 B12 o Shilling test Lack if evidence to determine if it is a better indicator than serum o Antibodies to IF Deficiency o Stages Determines problems with absorption related to Intrinsic Factor Give oral radioactive B12 Measures urinary excretion Lower than normal urinary excretion problems with absorption Not used in the US Proteins made in the body that affects Intrinsic Factor secretions Serum low levels of holotranscobalamin transcobalamine w o B12 it is an empty carrier Cell concentrations of vitamin diminish Biochemical deficiency Decreased DNA synthesis High homocysteine in serum o High risk for heart disease o Low metathione low SAM used for nerve function High methylmalonoic acid in serum Megaloblasic macrocytic anemia May be caused by pernicious anemia due to the lack of Intrinsic Factor o Autoimmune condition o Antibodies attack Parietal cells o Decreased IF production General syx Pale skin shortness in breath insomnia abnormal gait dementia fatigue palpitations paresthesia loss of concentration and neurological problems o At Risk Groups Malabsorptin Atrophic gastritis small stomach Gastrorectomy Aclorhydria lower HCL in stomach Decreased absorption area in stomach Medications that lower B12 o Antacids Proton pumps H2 blockers Decreased intake malabsoprtion extrinsic or EHC B12 transport Vegetarian diet Mutation TC2 Roughly 20 of population o Severe B12 deficiency Neurological problems Degeneration of spinal cords Presentations Absent reflexes ataxia no sense of touch Results servers irreversible brain and nervous tissue damage or Treatment death o Oral supplements if primary deficient and able to absorb o IM injections gets it straight into the body Toxicity None recorded and no UL Folate B9 The reason we began enriching B vitamins Follium latin means leaf Folate first isolated from spinach RDA Need to know these o Males and Females 19 30 400 micrograms d o Perinatal 600 micrograms o Lactating 500 micrograms Sources o Foods Mushrooms Spinach 131 for cup Greens Peanuts Legumes 130 150 for cup Citrus fruit Fortified cereals o Folacin term used to describe compound similar in structure and nutrition properties to folate Folate natural beef liver has a lot Folic Acid synthetic form supplements and fortified foods In 1998 they started putting 140 micrograms in 100 g of product Forms o Monoglutamates one glutamic acid Found in supplements and fortified foods Best way to transport o Polyglutamates 2 9 glutamates Found in cells Biologicall active form is tetrahydrofolate THF Structure o Folate Glutamic acid PABA Pteridine Our body can make all 3 parts but cannot link them together so Digestion folate must be eaten o Eaten as polyglutamates and monoglutamates o Conjugases Zn dependent on the brush border Cleaves polygluatamates into monoglutamates Found in parts of the intestine Jejunal mucosa Brushborder Zn dependent Pancreatic juices Bile Conjugase inhibitors legumes lentils cabbage oranges Absorption o Proton coupled folate transporter PCFT Genetic defect will cause folate deficiency o Enterocyte Folic Acid Folate Dihydrofolate NADPH Dihydrofolate reductase Dihydrofolate Tetrafolate NADPH Dihydrofolate reductase Transport o Portal systems monoglutamates o Uptake at tissues Carriers Reduced folate carriers Proton coupled transporters FR alpha FR beta FR gama Inside cell 4 8 glutamate residues are attached o Now trapped in cell and tuned into polyglutamate Conversion to coenzyme form THP Co enzyme form functions o Mechanism of action Accepts C groups from metabolic reactions Donates C groups for synthesis reactions o Amino Acid Metabolism Histidine
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