Exam 2! Cobalamin (B12)- RDAo Males and females (19-30) is 2.4 micrograms- Sources- can also be made by bacteriao Foods Animal products - Meat- Poultry- Fish, clams, and oysterso Very high amounts- Eggs- Milk No plant products- Vegetarians needs supplements Kumbacha, Batabuta, or fermented teas?- Formso Cobalamin Generic term for group of compound is called corrinoids- Corrin Nucleuso Macricyclic ring of 4 pyrrole ringso 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 charto CH3 = methylcobalamino 5’deoxyadenosyl= adenosylcobalamino Meat Products Adenosylcobalamin Hydroxocobalamino Milk Products Methylcobalamin Hydroxocobalamin o Supplements Cyanocobalamin Hydroxocobalamin- Digestion and Absorptiono Eaten in all formso 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 intestingo Small Intestine Cobalamin in released from R-Protein by pancreatic proteases Intrinsic factor binds to cobalamin Illeum- Pharmacological doses- passive diffusion- Dietary doseso Cubilins- receptor for B12o B12 + IF- enter cell by receptor mediated endocytossi Denterohepatic Circulation- Bileo 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 livero Tissues Uptake at tissues- Receptor for TC2- Receptor mediated endocytosis- Lysosome degrades TC2- Free B12 inside tissue- Storageo Liver- main storage site and can be stored for up to 11 yearso Lesser amounts stored in: muscle, kidneys, brain, bone, heart, spleen, & blood (as trans cobalamin)- Enzymatic Reactionso HomocysteineMethionine 2 step process- Formation of Methylcobalamin- Methylcobalamin donates methyl group to Homocystein form cobalamin and Methionineo MethylmalonylSuccinyl- CoA Succinyl-CoA is a krebb cycle intermediate 5-deoxyadenosylcobalamine Propionyl-CoAMethylmalonyl-CoA- Uses Biotin (B6) Methylmalonyl-CoASuccinyl-CoA- Adenosylcobalamin (B12) OR Methylmalonyl-CoAMethylonoic Acid- No B12 present (deficient) - Excretiono Urine- very littleo 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 testso Serum B12- Not the best way Serum levels can be falsely high or low with conditions or other diseaseso Methylmalonic acid Increased with B12 deficiency Serum or Urinaryo Homocysteine Increased with B12 deficiency and other factorso Deoxyuridine Supression Test (DUST) Impaired thymidine synthesis due to lack of B12 Complicated and expensive Also seen in Folate testso TC2 Lack if evidence to determine if it is a better indicator than serum B12o Shilling test 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 USo Antibodies to IF Proteins made in the body that affects Intrinsic Factor secretions- Deficiencyo Stages 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 diseaseo 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 Factoro Autoimmune conditiono Antibodies attack Parietal cellso Decreased IF production General syx- Pale skin, shortness in breath, insomnia, abnormal gait, dementia, fatigue, palpitations, paresthesia, loss of concentration, and neurological problemso At Risk Groups Malabsorptin- Atrophic gastritis- small stomach- Gastrorectomy- Aclorhydria (lower HCL in stomach)- Decreased absorption area in stomach- Medications that lower B12o Antacids Proton pumps H2 blockers Decreased intake- malabsoprtion extrinsic or EHC (B12 transport- Vegetarian diet Mutation TC2- Roughly 20% of populationo 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 death- Treatmento Oral supplements- if primary deficient and able to absorbo IM injections- gets it straight into the body- Toxicity- None recorded and no ULFolate (B9)- The reason we began enriching B vitaminsFollium (latin) means leafFolate first isolated from spinach- RDA- Need to know theseo Males and Females (19-30)- 400 micrograms/do Perinatal- 600 microgramso Lactating- 500 micrograms- Sourceso Foods Mushrooms Spinach- 131 for ½ cup Greens Peanuts Legumes- 130-150 for ½ cup Citrus fruit Fortified cerealso Folacin- term used to describe compound similar in structure and nutritionproperties 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- Formso Monoglutamates- one glutamic acid Found in supplements and fortified foods Best way to transporto Polyglutamates- 2-9 glutamates Found in cells Biologicall active form is tetrahydrofolate (THF)- Structureo Folate= Glutamic acid + PABA + Pteridine Our body can make all 3 parts, but cannot link them together so folate must be eaten- Digestiono Eaten as polyglutamates and monoglutamateso 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- Absorptiono Proton coupled folate transporter (PCFT) Genetic defect will cause folate deficiencyo Enterocyte Folic Acid & FolateDihydrofolate- NADPH- Dihydrofolate reductase DihydrofolateTetrafolate- NADPH- Dihydrofolate reductase- Transporto Portal systems- monoglutamateso Uptake
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