Cobalamin And Folate Flashcards
folate and vitamin B12
_____-soluble vitamins important in the formation of ______ cells, the _____ system, and _____
Water
red blood
nervous
DNA
Folic acid and vitamin B12
Required for _____ synthesis and ______ maturation
Two vitamins combine in ______ reaction
______ group is transferred to _____ to make ______
Premature _____ Disease
Peripheral _______ Disease
DNA; red cell
methionine synthase
Methyl; homocysteine; methionine
Coronary Artery
Vascular
Decrease in either cobalamin or folate leads to ___ease in homocysteine level
Incr
Deficiency of cobalamin and not folate, leads to change in RBC shape
T/F
F
It’s both
Megaloblastic erythropoiesis is when there is defect in ________ and the cells are arrested at the ____ phase
DNA synthesis; G2
Effects of folate deficiency
Main manifestations
______, symptoms of _____, and ____ problems
glossitis
anemia
GI
Effects of folate deficiency
Lab work
____ease in MCV– (smaller or larger?) than ____
Incr
Larger
96 fL
Best test for folate levels is the _________ level
this is the level in _____ and is not affected by ______
red blood cell
tissues
recent intake
Recommended intake of folate for adults is ____ micrograms per day, and for women of childbearing age is ____ micrograms per day
400
600
Effects on the Body—vitamin B12 deficiency
Main manifestations
same as those for folate but may be a more serious presentation with peripheral _________, degeneration of the _____, or ___ of ____ matter of brain
peripheral neuropathy
spinal cord
demyelination; white
Effects on the Body—vitamin B12 deficiency
Patient may present with difficulty ____, _____ , loss of _____ function, and a positive _____ test
walking
parasthesia
memory; Romberg
Recommended intake of vitamin B12 for adults is ____ micrograms per day, and for women of childbearing age is ___ micrograms per day
2.4
2.6
The word folic acid is derived from the latin word _____ which means ____.
folium
Leave
Folic acid consist of 3 component:
______
________
________ residue (___ residue)
Hence it is known as ________
Pteridine ring
PABA ( P amino benzoic acid)
Glutamic acid; 1-7
Pteroyl-glutamic acid
Absorption of folate
Poly glutamate, The ______ side chain are cleaved by the enyzme _______ or ___________
glutamate
folate conjugase
polypolyglutamase hydrolase.
Most of the dietary forms of folate exist as _________
polyglutamate
Absorption of folate
Poly glutamate can be absorbed in the intestine.
T/F
F
Absorption of folate
Only the _______ form is absorbed from the intestine
monoglutamyl
The enzyme folate conjugase is present in the ____________
duodenum and jejunum
Absorption of folate
Mucosal uptake and metabolism in the mucosal cell
In the mucosal cell folate _______ is reduced to ______ and ____ to form __________ in circulation
monoglutamate
tetrahydrofolate
methylated
N 5 methyl tetrahdrofolate
Storage of folate
Inside the cell, tetrahydrofolate are found as ______ with ___ amino acid residue
polyglutamate
5-6
______ version of folate is most potent
Polyglutamate
5-6 residue
_______ is the storage form of folic acid.
Polyglutamate
Folate mainly stored in the ____ (10-20mg)
liver
Folic acid is biologically active
T/F
F
It is not
The active coenzyme forms of folic acid are:
_____________ (____)
______________
______________ (______)
_________________ (_______)
N5 methyl tetrahydrofolate ;N5FH
N5 N10 methylene tetrahydrofolate
N10 formyl tetrahydrofolate ; N10 formyl FH4
N5 formimino tetrahydrofolate; N5 formimino FH4
The coenzyme of folic acid are actively invovled in the ____ metabolism.
one carbon
THF acts as an acceptor or donor of one carbon unit (_____,_____,______,______etc)in reaction involving _______ and ——- metabolism.
formyl,methyl , methylene, methynyl
amino acids and nuclotide
The one carbon units bind with THF at position __________________________ of pteroyl structure
N5 or N10 or on both N5 & N10
All of the biological functions of folic acid are performed by ___ and its _____ derivatives.
Hence folic acid must first be reduced to ______.
THF
methylated
THF
Reduction of folic acid to THF
This —— electron reduction proceeds in two chemical steps both catalyzed by the same enzyme,_________
Folic acid is first reduced to ______ and then to ________.
Each step consumes ___ molecule of ____ (biosynthetically derived from ______) and produces one molecule of _____.
four; dihydrofolate reductase
dihydrofolate; tetrahydrofolate
one; NADPH; vitamin B3
NADP
Reduction of folic acid to THF
Mechanistically, _____ is transferred from NADPH to the ____ position of the ________
hydride; C6
pteridine ring
One carbon atom reaction
A one-carbon (1C) methyl group is added to tetrahydrofolate through the action of ________________ to yield ____________
This reaction also consumes _______ and _______ and produces ______ and _____
serine hydroxymethyltransferase (SHMT)
5,10-methylenetetrahydrofolate(5,10-CH2-THF).
serine and pyridoxal phosphate
glycine and pyridoxal.
One carbon atom reaction
A second enzyme, ___________ oxidizes ________ to an iminium cation which in turn is ______ to produce _______ and _______
methylenetetrahydrofolate dehydrogenase (MTHFD2)
5,10-methylenetetrahydrofolate
hydrolyzed
5-formyl-THF and 10-formyl-THF
Synthesis of Deoxythymidylate (dTMP)
________________ transfers a methyl group to ________ to form ______
N5,N10-methylene tetrahydrofolate
deoxyyuridylate (dUMP)
dTMP
dTMP is Essential for DNA synthesis.
T/F
T
N5,N10-methylene tetrahydrofolate is absolutely essential for __________
This is important in rapidly dividing cell eg ______,_______,_______,________ cells .
DNA synthesis.
RBC , hair follicles, intestinal mucosa cells and cancer
_________ (analogue of folic acid)
Methotrexate
Which binds better to folate reductase ?
Methotrexate or folate?
Methotrexate binds to folate reductase 1000 times more tightly than folate.
Methotrexate inhibits the conversion of ________ and _______ into active tetrahydrofolate
folate and dihydrofolate
Rich sources of folate are _____________ such as spinach, cauliflower
Poor sources of folate are ____,____,_____,____
green leafy vegetables
liver, kidney ,milk ,fruits
Folic acid deficiency
Dietary deficiency
This include:
Inadequate intake seen in _______
________ of food resulting in loss of folic acid activity
Impaired absorption due to __________
Drug interfere with folic absorption – _______
Increase demand in _______
alcholics
Overcooking
small intestinal disease
pregnancy
_________ is the most common cause of folic acid deficiency
Dietary deficiency
Causes of folic acid deficiency
________ anaemia
Loss of folic acid seen in patient undergoing ______
Impaired synthesis of active form seen in patients receiving _______ such as ______
Haemolytic
dialysis
folic acid antagonist
methrotrexate
Clinical features of folic acid deficiency
______ anaemia charaterised by ___chromic ___cytic anaemia ( due to ________)
Megaloblastic changes are seen in marrow & mucosa
Patient look ____
_________
Megaloblastic; hyper; macro
maturation block
pale
Glossitis
Laboratory findings in folate deficiency
Peripheral smear: ___cytic ___chromic anaemia
Hyper____ _______
macro; hyper
segmented
neutrophils
In pregnancy folic acid helps prevent _____
Mainly involve the ______ and _____
deficiency result in impaired and aberrant neural development.
neural tube defects
brain and spinal cord,
Homocyteinaemia is a risk factor for ____
CHD
Folic acid is required for the conversion of homocyteine to ______
methionine
Homocysteine level is also increased in vit.______ and _____ deficiency
B12
pyridoxine
Cobalamin is an analogous to ____ in its ______ having as its base a ______ ring.
heme
structure
tetrapyrole
Instead of iron as a metal co factor for heme, cobalamin has _____ in a coordination state of _____ with;
A ________ group nitrogen coordinated to a one axial position.
The 4 equatorial positions coordinated by the ________ of ________ group and
cobalt; six
benzimidazole
nitrogens of 4 pyrrrole
Cobalamin (vitamin B12) exit in a number of different chemicaal forms.
All have a _____ atom at the centre of a _____ ring.
colbalt; corrin
Forms of cobalamin
In nature it is mainly in the ________, form which is located in the _________
The other major natural cobalamin is _________, the form in _______ and ______
There are also minor amount of __________ to which methyl and adenosyl are rapidly converted to by exposure to ____
2-deoxyadenosyl (ado)
mitochondria
methylcobalamin; human plasma and cell cytoplasm.
hydroxocobalamin;
Light
Cobalamin is synthesized solely by _______.
microorganism
Strict ________ are at risk of developing B12 deficiency
vegetarians
Ruminants obtain cobalamin from the ______, but the only source for human is _______ of _____ origin
Fish
Meat
Dairy product
foregut
food of animal origin.
Absorption of cobalamin
Two mechanism exist:
Passive absorption- occuring through _____,_____,_____ mucosa; it is (slow or rapid?) but extremely inefficient,<___% of an oral dose being absorbed by this process
buccal, duodenal and ileal
Rapid ; 1
Absorption of cobalamin
Two mechanism exist:
_________
__________
Passive absorption
Active absorption
Absorption of cobalamin
Two mechanism exist:
Active absorption- normal physiologic mechanism is active; it occurs through the _____ and is efficient for small(a few microganism)oral doses of cobalamin and is mediated by ________
iluem
gastric intrinsic factor (IF)
Absorption of cobalamine
Dietary cobalamin is released from protein complexes by enzymes in the ____,_____,_ and _____
It combines (slowly or rapidly?) with _______ that belongs to the family of cobalamin-binding protein known as _________ which are digested by ______ and the cobalamin transferred to intrinsic factor (IF)
stomach, duodenum and jejunum.
Rapidly ; salivary glycoprotein
pancreatic trypsin
Role of intrinsic factor
Intrinsic factor is produced in the ____ cells of the ______ and ______ of the stomach, and its secretion parellels that of _________
parietal
fundus and body
The intrinsic factor -cobalamin complex passes to the the _____, where IF attaches to a specific receptor ( ____) on the microvillus membrane of the enterocytes.
iluem
cubulin
Cubulin with its ligand IF-cobalamin complex is ________.
The complex enters the _____ cell where _______
endocytosed
ileal
IF is destroyed.
In the absence of IF, inadequate amount of cobalamin are absorbed resulting in _________ anaemia.
megaloblastic
the dietary requirement is appx. ____ng/day)
200
When the root cause of the resultant megaloblastic anaemia is absence of or inadequate amount of IF the condition is called _________ anaemia.
pernicious
Transportation of cobalamin
Three plasma transport protein have been identified:
________
_______/________
______
Intrinsic factor
Transcobalamin I; haptocorrin
Transcobalamin II
Transcobalamin is secreted by _______
white cell.
Although approx. —% of plasma vit.B12 in circulation binds to the transport proteins only ___________ is capable of transporting vitamin B12 into cells.
90
transcobalamin II
The body usually has sufficient stores of vitamin b12
T/F
T
So Vit.B12 deficiency develops more than ______ after absoption ceases.
3 years
Cobalamin plays a vital role in the catabolism of ________, threonine, ______ and the ______ amino acids (leucine,isoleucineand valine.
The degradation of these compounds produces the same metabolite ________
odd-chain fatty acids
methionine
branchede chain
Propionyl CoA.
Cobalamin in In DNA synthesis
It’s the biochemical basis for the development of ________ specifically the _______ synthesis reaction which converts ______-_____
megaloblatics anaemia
thymidylate
dUMP - dTMP
Cobalamin In Methionine metabolism
Its required for the conversion of ___________ into ______
Cobalamin must undergo _______ first tho to _______ and it recieves the group from ______________ thus regenerating ————- that participate in the other one carbon transfer in ____metabolism or ______ remodeling.
homocysteine into methionine.
Methyl transfer
methyl cobalamin.
N5 –methyl tetrahydrofolate
tetrahydrofolatet
purine ; pyrimidine
Vit B12 is important in conversion of ______ to _______ in Krebs cycle.
In this reaction B12 acts as co-enzyme for _____________
methylmalonyl CoA
succinyl CoA
methylmalonyl Co A mutase.
Vitamin B12 is Necessary in the synthesis of _____ from homocysteine.
In this reaction ________ are involved.
B12 acts as a co-enzyme (______) for ________.
methionine
both vit B12 and folic acid
methyl cobalamin
methyltransferase
Causes of vitamin B12 deficiency
_____ deficiency (rare)
_______ anaemia( most common case of Vit.B12 )
______tomy
_______ insufficiency
__________ (rare)
___________ infection.
Dietary; Pernicious
Gastrec
Pancreatic
Fish tape worm
Helicobacter pylori
Causes of vitamin B12 deficiency
_______ disease
Surgical resection
Decrease _____ absorption of vit.B12
_________ deficiency (rare)
_______ syndrome
Crohn’s
ileal
Transcobalamine II
Blind loop
FOLATE TRAP
In cobalamin deficiency, the methionine synthase reaction cannot occur, __________ accumulate and the other C-1 donor forms of tetrahydrofolate cannot be formed.
The methionine synthesis from homocysteine ceases , allowing the “trapping” of the folate pool as ______, thereby diminishing level of _______________ which is required for the methylation of ____ to ____ , thus in its deficiency, the ________ reaction is slow and _____ levels drops and hence _____ synthesis is also slowed down due to non availability of ______.
N5-methyltetrahdrofolate
N5 methyltetrahdrofolate
N5,N10 methylenetetrahdrofolate.
dUMP to dTMP
thymdilate synthase ; dTMP
DNA; deoxyribonucluotide
MEGALOBLASTIC ANAEMIA
The Hall mark of symptomatic vitamin B12 deficiency is ______________
In advance cases the anaemia may be severe with haematocrit as low as ___% an may be accompanied with _____ and ______
The megaloblastic state also produces changes in mucosal cells, leading to _____, as well as other vague ______ disturbances such as _____ and diarrhea.
Patients are usually ____ and may be midly _____.
megaloblastic anaemia.
10-15
lecopenia and thrombocytopenia.
glossitis; gastrointestinal; anorexia
pale; icteric
Biochemical findings in folic acid deficiency
Low plasma folic acid level < ___ng/ml
Low red cell folic acid level < ____ng/ml
_______ pLasma vit.B12
_____ease plasma LDH
3
150
Normal
Incr
Folic acid excretion test:
Folic acid deficiency is associated with increase excretion of _________ in urine. Due to impaired converssion of ____ to _____ in a reaction requiring ______
formiminoglutamate ( FIGLU)
FIGLU; glutamate
FH4
Vitamin B-12
Normal diet contains btw 5-30 ug of cobalamin daily
Adult daily losses mainly in urine and feaces are between __-___ug (~0.1% of body stores) as the body does not have the ability to degrade cobalamin.
Daily reqiurement is about ___-____ug.
Body stores of __-___ mg, sufficient for__-___ years if supplies are not cut off
1-3
1-3
2-3
3-4
Cobalamin binds to _____ (aka ____, _____) to protect it from acid in the stomach.
This is destroyed in the intestine by _____ so that cobalamin can bind to ______
R protein(Transcobalamin 1, haptocorrins)
Pancreatic trypsin
Intrinsic factor
