Exam 2 Study Guide B12 Cobalamin I Sources A Can be made by bacteria B Animal Products 1 Meat poultry fish 2 Clams and oysters 3 Milk and milk products in lesser amounts C NO Plant Products 1 B12 is an issue with vegetarians and vegans and more than likely will need supplementation ranging from lacto ovo vegetarians to vegan D Kombucha tea and Batabata cha are fermented teas that do NOT have enough B12 to E Supplements are highly recommended but products as shown in the table in slide 3 do meet bodily needs not always supplement with B12 II Forms A Cobalamin is the generic term for the group of compounds called corrinoids The corrin nucleus contains macrocyclic rings of 4 pyrrole rings For B12 there is a cobalt attached to the corrin 1 The group attached to the cobalt determines the form of Cobalamin One form can turn into the other for example if we eat cyanocobalamin we can swap out the functional groups to make adenosylcobalamin B Meat Products Adenosylcobalamin and hydroxocobalamin C Milk Products Methylcobalamin and hydroxocobalamin D Supplements Cyanocobalamin and hydroxocobalamin Digestion and Absorption A Eaten B Stomach in ALL forms 1 Pepsin and HCl release Cobalamin from polypeptides 2 R Proteins Cobalophilins or haptocorrins are found in saliva and gastric juices R Proteins bind to the now free B12 3 Intrinsic Factor IF is made in the stomach but does not function is not used until it reaches the small intestine C Small Intestine 1 Here Cobalamin is released from the R Protein by pancreatic proteases 2 IF binds to the freed B12 3 In the Ileum pharmacological doses are absorbed via Passive Diffusion For dietary doses need cubilins the receptors for B12 B12 and possibly the IF enter into the cell by receptor mediated endocytosis IF is necessary for absorption but we don t know if it is absorbed into the cell with B12 III D Enterohepatic Circulation 1 B12 is eaten attached to proteins 2 Protein B12 is broken by pepsin and HCl 1 At the same time we are making R Protein and IF 3 B12 binds to the R Protein 4 B12 is broken off R Protein by proteases 5 B12 binds to IF 6 B12 enters cell by receptor mediated endocytosis 7 B12 enters the bloodstream to the liver Anything that goes wrong in this system whether not making or using IF and therefore not absorbing B12 can cause a B12 deficiency Also affected by the acidity of the stomach E Transport transported when bound to one of the 3 transcobalamins 1 TCI circulating storage form 2 TCII carries newly absorbed Cobalamin to tissues from enterocyte to liver 3 TCIII delivery from peripheral tissues to liver and vice versa F Tissues when we want to get B12 in and out of tissues we need receptors 1 Receptor for TCII 2 Receptor mediated endocytosis 3 Lysosome degrades TCII and B12 is free inside the cell The receptor and TCII then recycle back to the surface of the cell G Storage The liver is the main site stored as adenosylcobalamin for up to 11 years It can take 15 years to see a deficiency Lesser amounts are stored in muscle kidneys brain bone heart spleen and circulating in the blood as transcobalamin B12 plays a Huge Role in 2 Enzymatic Reactions 1 Homocysteine methylcobalamin then methylcobalamin donates a methyl group to form Cobalamin and Methionine This is a 2 step process first with the formation of Methionine It is also involved in turning Folate into its functional form a b This is a win win reaction as it gets folate into its usable form and decreases the c amount of homocysteine in the body If missing B12 we cannot take the methyl group off of 5 methyl THF and are stuck in the Methyl Folate Trap methyl group is trapped on folate and folate cannot be used and we are left with homocysteine 2 Formation of Succinyl CoA from methylmalonyl using 5 deoxyadenosylcobalamin a Succinyl CoA is a Krebs intermediate Propionyl CoA Metylmalonyl CoA Succinyl CoA adenosylcobalamin Biotin IV V VI Excretion A Urine very little due to True Storage B Bile enterohepatic circulation C Can be stored in the body for up to 11 years Assessment A Main Tests 1 Serum B12 Plasma Levels serum levels can be falsely high or low with conditions or other diseases 2 Methylmalonic acid increases with B12 deficiency are is found in serum and 3 Homocysteine increases with B12 deficiency but can also be from a variety of problems and therefore is not a definitive test urine B Other Tests 4 Deoxyuridine Suppression Test DUST impaired thymidine synthesis due to lack of B12 due to the lack of Folate It is complicated and expensive and not definitive 5 TCII no TCII means not absorbing B12 There is a lack of evidence to determine if it is a better indicator than a serum B12 test 6 Shilling test used to be the most common determines problems with absorption related to the IF Given oral radioactive B12 and measure urinary excretion lower than normal urinary excretion means there is a problem with absorption Not done in the US 7 Antibodies to IF making antibodies anti IF in body VII Deficiency Is in stages Serum low levels of holotranscobalamin II a preprotein protein without B12 attached Cell concentrations of vitamin diminish Biochemical deficiency occurs and really see outward symptoms here 1 Decreased DNA synthesis 2 Elevated homocysteine in serum Increased homocysteine which is a Risk Factor for CVD Decreased methionine which leads to decreased SAM essential in nerve function 3 Elevated methylmalonic acid in serum Megaloblastic macrocytic anemia big immature RBCs 1 May be caused by pernicious anemia an autoimmune condition where you produce antibodies that attack the parietal cells This causes a decrease in IF production 2 Someone is eating B12 but cannot produce IF General symptoms pale skin shortness of breath insomnia abnormal gait dementia fatigue palpatations paresthesia loss of concentration neurological problems At risk populations Malabsorption 1 Atrophic gastritis smaller stomach 2 Gastrectomy 3 Aclorhydria lack of stomach acid 4 Decreased absorptive area in the intestine bypass or Crohn s disease 5 Medications proton pumps or H2 blockers are antacids that reduce stomach acid 6 Malabsorption extrinsic and EHC Decreased Intake 1 Vegetarian diets 2 Mutation of TCII 20 of the population have problems with TCII VII VIII Treatment A Primary deficiency oral supplementation sublingual B Secondary deficiency Intermuscular IM injections Toxicity None no UL set B9 Folate I Sources mainly in vegetables A Foods i Mushrooms ii Green vegetables iii Peanuts iv Legumes v
View Full Document
Unlocking...