05vitamins_b6_b12_ 22.10.2011[1]
TRANSCRIPT
-
8/12/2019 05Vitamins_B6_B12_ 22.10.2011[1]
1/29
Vitamins B 6 and B 12
General biochemistryFunctionsDeficiency diseases
Dr. Sumbul Fatma
-
8/12/2019 05Vitamins_B6_B12_ 22.10.2011[1]
2/29
Classification of Vitamins
-
8/12/2019 05Vitamins_B6_B12_ 22.10.2011[1]
3/29
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
-
8/12/2019 05Vitamins_B6_B12_ 22.10.2011[1]
4/29
Vitamin B Complex
Present in small quantities indifferent types of foodImportant for growth and goodhealthHelp in various biochemical
processes in cellFunction as coenzymes
-
8/12/2019 05Vitamins_B6_B12_ 22.10.2011[1]
5/29
Vitamin B 6
Three formsPyridoxinePyridoxalPyridoxamine
Active formAll 3 are converted to pyridoxal phosphate(PLP)
-
8/12/2019 05Vitamins_B6_B12_ 22.10.2011[1]
6/29
-
8/12/2019 05Vitamins_B6_B12_ 22.10.2011[1]
7/29
Functions of Vitamin B 6
As coenzyme forTransamination DeaminationDecarboxylationCondensation reactions
-
8/12/2019 05Vitamins_B6_B12_ 22.10.2011[1]
8/29
-
8/12/2019 05Vitamins_B6_B12_ 22.10.2011[1]
9/29
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
-
8/12/2019 05Vitamins_B6_B12_ 22.10.2011[1]
10/29
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)]
-
8/12/2019 05Vitamins_B6_B12_ 22.10.2011[1]
11/29
Disorders of Vitamin B 6
Deficiency PLP is involved in the synthesis ofsphingolipids
Its deficiency leads to demyelination ofnerves and consequent peripheralneuritis
-
8/12/2019 05Vitamins_B6_B12_ 22.10.2011[1]
12/29
Disorders of Vitamin B 6
Deficiency Mild deficiency involves:IrritabilityNervousnessDepression
Severe deficiency involves:
Peripheral neuropathyConvulsions
-
8/12/2019 05Vitamins_B6_B12_ 22.10.2011[1]
13/29
Forms of Vitamin B 12
CyanocobalaminHydroxycobalamin
Adenosylcobalamin (major storage form inthe liver)Methylcobalamin (mostly found in bloodcirculation)
-
8/12/2019 05Vitamins_B6_B12_ 22.10.2011[1]
14/29
Coenzyme forms of B 12
Adenosylcobalamin and MethylcobalaminCoenzymes for metabolic reactions
Body can convert other cobalamins intoactive coenzymes
-
8/12/2019 05Vitamins_B6_B12_ 22.10.2011[1]
15/29
-
8/12/2019 05Vitamins_B6_B12_ 22.10.2011[1]
16/29
Vitamin B 12(Cobalamin)
Mainly found in animal liverbound to protein as
Methylcobalamin or5-deoxyadenosylcobalamin
-
8/12/2019 05Vitamins_B6_B12_ 22.10.2011[1]
17/29
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
-
8/12/2019 05Vitamins_B6_B12_ 22.10.2011[1]
18/29
-
8/12/2019 05Vitamins_B6_B12_ 22.10.2011[1]
19/29
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
-
8/12/2019 05Vitamins_B6_B12_ 22.10.2011[1]
20/29
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
-
8/12/2019 05Vitamins_B6_B12_ 22.10.2011[1]
21/29
Functions of Vitamin B 12
(2) Conversion ofhomocysteine tomethionine
Methionine synthaserequires B 12 in convertinghomocysteine tomethionine
-
8/12/2019 05Vitamins_B6_B12_ 22.10.2011[1]
22/29
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
-
8/12/2019 05Vitamins_B6_B12_ 22.10.2011[1]
23/29
Interconversionbetween TH4 carrier
of one - carbon units
-
8/12/2019 05Vitamins_B6_B12_ 22.10.2011[1]
24/29
Disorders of Vitamin B 12 Deficiency
Pernicious anemiaMegaloblastic anemia
Vitamin B 12 deficiency is mainly dueto the deficiency of intrinsic factor
-
8/12/2019 05Vitamins_B6_B12_ 22.10.2011[1]
25/29
Disorders of Vitamin B 12 Deficiency
DemyelinationMyelin sheath of neurons ischemically unstable anddamaged
NeuropathyPeripheral nerve damage
-
8/12/2019 05Vitamins_B6_B12_ 22.10.2011[1]
26/29
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
-
8/12/2019 05Vitamins_B6_B12_ 22.10.2011[1]
27/29
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)
-
8/12/2019 05Vitamins_B6_B12_ 22.10.2011[1]
28/29
Neuropsychiatric symptoms ofVitamin B 12 Deficiency
Psychiatric symptoms Confusion and memory loss
DepressionUnstable mood
-
8/12/2019 05Vitamins_B6_B12_ 22.10.2011[1]
29/29
References
Lippincotts Illustrated Reviews in MedicalBiochemistryTextbook of Medical Biochemistry withClinical Correlations by Thomas M DevlinHarpers Illustrated Biochemistry