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Vitamins B 6 and B 12
General biochemistryFunctionsDeficiency diseases
Dr. Sumbul Fatma
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Classification of Vitamins
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Water-Soluble Vitamins
B vitamins Thiamin (B 1), riboflavin (B 2), niacin (B
3),pantothenic acid (B 5), pyridoxine (B 6), biotin(B 7), cobalamin
(B 12 ), folate
Not significantly stored in the bodyMust be supplied regularly
in the dietExcess excreted
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Vitamin B Complex
Present in small quantities indifferent types of foodImportant
for growth and goodhealthHelp in various biochemical
processes in cellFunction as coenzymes
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Vitamin B 6
Three formsPyridoxinePyridoxalPyridoxamine
Active formAll 3 are converted to pyridoxal phosphate(PLP)
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Functions of Vitamin B 6
As coenzyme forTransamination
DeaminationDecarboxylationCondensation reactions
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Disorders of Vitamin B 6
Deficiency Dietary deficiency is rare, but it wasobserved
in:
Newborn infants fed on formulas low in B6Women on oral
contraceptivesAlcoholics
Isoniazid treatment for tuberculosis canlead to vitamin B 6
deficiency by forminginactive derivative with PLP
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Disorders of Vitamin B 6
Deficiency Deficiency leads to poor activity ofPLP-dependent
enzymes Causing:
Deficient amino acid metabolismDeficient lipid
metabolismDeficient neurotransmitter synthesis[serotonin,
epinephrine, noradrenaline and
gamma amino butyric acid (GABA)]
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Disorders of Vitamin B 6
Deficiency PLP is involved in the synthesis ofsphingolipids
Its deficiency leads to demyelination ofnerves and consequent
peripheralneuritis
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Disorders of Vitamin B 6
Deficiency Mild deficiency
involves:IrritabilityNervousnessDepression
Severe deficiency involves:
Peripheral neuropathyConvulsions
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Forms of Vitamin B 12
CyanocobalaminHydroxycobalamin
Adenosylcobalamin (major storage form inthe
liver)Methylcobalamin (mostly found in bloodcirculation)
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Coenzyme forms of B 12
Adenosylcobalamin and MethylcobalaminCoenzymes for metabolic
reactions
Body can convert other cobalamins intoactive coenzymes
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Vitamin B 12(Cobalamin)
Mainly found in animal liverbound to protein as
Methylcobalamin or5-deoxyadenosylcobalamin
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Vitamin B 12
Essential for normal nervous system functionand red blood cell
maturationNot synthesized in the body and must besupplied in the
dietBinds to intrinsic factor and absorbed by theileum
Intrinsic factor is a protein secreted by cells inthe
stomach
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Vitamin B 12 Storage
Liver stores vitamin B 12 (4-5 mg)
Other B vitamins are not stored in the body
Vitamin B 12 deficiency is observed in patientswith IF
deficiency due to autoimmunity or bypartial or total
gastrectomy
Clinical deficiency symptoms develop inseveral years
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Functions of Vitamin B 12 Two reactions require B
12
(1) Conversion ofpropionyl-CoA tosuccinyl-CoA
The enzyme in thispathway, methyl-
malonyl-CoA mutase,requires B 12
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Functions of Vitamin B 12
(2) Conversion ofhomocysteine tomethionine
Methionine synthaserequires B 12 in convertinghomocysteine
tomethionine
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B 12 Deficiency and Folate Trap
Homocysteine re-methylation reaction is theonly pathway where N
5-methyl TH4 can bereturned back to tetrahydrofolate poolHence
folate is trapped as
N5-methyltetrahydrofolate (folate trap)
This leads to folate deficiency and deficiencyof other TH4
derivatives (N 5-N10 methyleneTH4 and N 10 formyl TH4) required for
purineand pyrimidine syntheses
TH4: Tetrahydrofolate
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Interconversionbetween TH4 carrier
of one - carbon units
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Disorders of Vitamin B 12 Deficiency
Pernicious anemiaMegaloblastic anemia
Vitamin B 12 deficiency is mainly dueto the deficiency of
intrinsic factor
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Disorders of Vitamin B 12 Deficiency
DemyelinationMyelin sheath of neurons ischemically unstable
anddamaged
NeuropathyPeripheral nerve damage
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Disorders of Vitamin B 12 Deficiency
Causes of neuropathy Deficiency of vitamin B 12 leads
toaccumulation of methylmalonyl CoAHigh levels of methylomalonyl
CoA isused instead of malonyl CoA for fattyacid synthesisMyelin
synthesized with these
abnormal fatty acids is unstable anddegraded causing
neuropathy
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Neuropsychiatric symptoms ofVitamin B 12 Deficiency
Neurological symptoms Paraesthesia (abnormal sensation) ofhands
and feetReduced perception of vibration andposition
Absence of reflexesUnsteady gait and balance (ataxia)
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Neuropsychiatric symptoms ofVitamin B 12 Deficiency
Psychiatric symptoms Confusion and memory loss
DepressionUnstable mood
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References
Lippincotts Illustrated Reviews in MedicalBiochemistryTextbook
of Medical Biochemistry withClinical Correlations by Thomas M
DevlinHarpers Illustrated Biochemistry
