Vitamin B12 and Folate Metabolism Flashcards
In DNA synthesis, _______ acting as a coenzyme and ______ as a cofactors
B12, Folate
Provides Methylation for the conversion of homocysteine to ________
Methionine
Provides Methylation for the conversion of deoxyuridine monophosphate (dUMP) to __________
Deoxythymidine Monophosphate (dTMP)
What is the average dietary intake of B12
20
What is the average dietary intake of folate
250
What is the major food source of Vitamin B12
Animal Produce only
What are the major food sources of Folate
Liver, Vegetables
How long is the normal body store for Vitamin B12
Several years
What long is the normal body store for folate
A few months
What is the mode of absorption for Vitamin B12
It combines with the transport protein intrinsic factor secreted by gastric parietal cells - then absorbed through ileum via special receptors
What is the mode of absorption for folate
Converted to Tetrahydrofolate and absorbed in the duodenum and jejeunum
Vitamin B12 is required as a Coenzyme for what two metabolic reactions
Isomerization of L-methylmalonyl CoA to succinylcholine CoA
-Important substrate I’m Hb synthesis
Methylation of Homocysteine to Methionine
-This step is important in intracellular synthesis of folate coenzyme
Folate and B12 is necessary for synthesis of ________
DNA
B12 deficiency causes Folate to be trapped in _______ form
Methyl Form
Tue or False, RNA synthesis is unaffected
True
The resultant deficiency in what substance affects DNA synthesis
Methylene FH4
What type of red cell are formed due to B12 and Folate deficiency
Large red cells with nuclear retention and a flimsy membrane
What type of disease is formed due to a lack of Folate and B12
Megaloblastic Anaemia
Where does B12 absorption occur
Illeum
Vitamin B12 is liberated from ______ protein by ______ and _____ enzymes and complexes in a 1:1 ratio with the _______
R protein, gastric and duodenal enzymes, intrinsic factor
What cells synthesize and and secrete IF
Gastric Parietal Cells
What is the MW of the glycoprotein IF
45,ooo
B12 attaches to specific receptors on the ileal mucosal Cells under what conditions
Calcium ions and a neutral pH
How long does it take for B12 to be released into circulation
6 hours
What are the two mechanisms of Cobalamin absorption
Passive Absorption and Active Absorption
Which mechanism of Cobalamin transport is insufficient
Passive Absorption
Where does the passive absorption of Cobalamin occur
Buccal, duodenal and ileal mucosa
True or False, passive absorption is Slow
False it is rapid
What is the Mode of Administration for Vitamin B12
Oral
True or False, the normal physiological mechanism for B12 absorption is active
True
What substance mediates oral doses of Cobalamin
Gastric IF
Dietary Cobalamin is released from protein complexes by enzymes in which 3 areas of the body
Stomach, Duodenum and jejunum
What is the name of the protein that binds to Dietary Cobalamin
Haptocorrins
In the intestines the haptocorrins are digested by the _________ enzyme and the Cobalamin is transferred to ________
Pancreatic trypsin, Intrinsic Factor
The IF is produced in the _______ of the fundus and body of the stomach, it’s secretions m parallels that of _________
Hydrochloric Acid
What receptor does the IF-Cobalamin complex attaches to in the ileum on the microvillus membrane of the Enterocytes
Cubulin
Cubulin with its ligand IF-cobalamin complex is ________. Where it enters the ileal cell, the _______ is destroyed.
Endocytosed , IF
What is the collective name for the B12 transport proteins normally present in the plasma
Transcobalamines
What is the name of the 3 Transcobalaminese
TCI-TCII-TCIII
What is the name of the physically active transcobalamine that is physiologically active in the 1:1 ratio with Vitamin B12
TCII
Where does the TCII- B12 complex bind
Developing blood cells in the bone marrow
The Transcobalamines I and II are what type of globulins
Alpha
The Transcobalamines I and III are synthesized by what type of cells
Granulocytes
What is another name for Transcobalamines and where are they found
R binders in gastric juices
What two types of Transcobalamines do not release Vitamin B12 readily to developing tissues
TCI and TCIII
True or False, the congenital abscence of TCI and TCIII will cause no physiological impairment
True
Where are Folates absorbed maximally
Upper Jejunum
Folate Polyglutamate must be digested to form __________ before Absorption
Monoglutamate
The absorbed folate is converted into __________, then releases into the portal blood stream
N-5- methyltetrahydrofolate
True or False, Folate functions as single carbon donor acceptor
True
What are the 5 ways in with folate acts as a single carbon donor- acceptor
Synthesis of Methionine. By donation of methyl group from N-5-methyl-tetrahydrofolate and requires Vitamin B12 as a coenzyme
Pyrimidine Synthesis, which is the rate limiting step in DNA synthesis
Purine Synthesis
Conversion of serine into glycine
Histidine Catabolism
What is the cause of Pernicious Anaemia
Failure of absorption of B12 due to lack of IF and autoimmune disorder
What abnormalities cause Pernicious Anaemia
Gastric cell Atrophy, Achlorhydria
What is the most common age group for Pernicious Anaemia
Women over 50 years
True or False, several years of malabsorption is required for deficiency to manifest
True
True or False, Subacute Combined Degeneration of the spinal cord (unsteady gait) is a resultant of Pernicious Anaemia
True
What are the causes of Vitamin B12 Deficiency
Inadequate dietary intake
Intestinal Malabsorption
Failure of utilization of Vitamin B12
What appears in urine when there is a failure to metabolize Vitamin B12
methylmalonic acid and homocysteine
True or False, the patients that fail to metabolize Vitamin B12, are usually mentally retarded but rarely develop megaloblastic Anaemia
True
What does Anaesthetic Nitrous Oxide do in the body
Inactivated Vitamin B12 coenzymes and induces megaloblastic changes and mild neuropathy
What causes Folic Acid deficiency
Inadequate diet
intestinal malabsorption
Excessive Alcohol usage
Failure of utilization of the absorbed Vitamin B12
What causes a failure of folate metabolism
Enzyme deficiencies associated with megaloblastic changes and mental retardation