Vitamin B6 and B12 Not Fat Soluble Water Soluble significantly stored in the Non-B-complex body (except B12) be Must C) (vitamin acid Ex.Ascorbic أكيد A,D,E,K supplied regularly in B-complex the diet B-complex Excess excreted

-Present in small quanes in different types of food -Important for growth and good health -Help in various biochemical processes in cell -Funcon as coenzymes

Energy-releasing Hematopoiec Other

Thiamine (B1) Folic Acid Pyridoxine (B6) Riboflavin (B2) Vitamin B12 Pyridoxal Niacin (B3) Pyridoxamine Bion Pantothenic acid Forms..? • Pyridoxine (plants) Vitamin B6 • Pyridoxal (animal source) • Pyridoxamine (animal) (PLP) acts as a coenzyme for the following Acve form..? reacons: All 3 are converted to pyridoxal phosphate (PLP) 90% in muscles. (next slide) 1. Condensaon Reacon. 2. Decarboxylaon Reacon: Formaon of • Formaon of Chatecholamines: Dopamine, aminolevulinic norepinephrine and epinephrine. acid (ALA) • Formaon of Histamine and Serotonin. by ALA synthase.. The regulatory step in hemoglobin synthesis It requires pyridoxal phosphate for formaon of (ala)

3. Transaminaon Reacon.

Allergy mediator 4. Deaminaon. Vitamin B6 Vitamin B6

Disorders of Vitamin B6 Deficiency..

Causes..? -Dietary deficiency is rare, but it was observed in: (more common in females) 1. Newborn infants fed on formulas low in B6 2. Women on oral contracepves 3. Alcoholics -Isoniazid treatment for tuberculosis can lead to vitamin B6 deficiency by forming inacve derivave with PLP.

Deficiency leads to..? -Poor acvity of PLP-dependent enzymes Causing: • Deficient amino acid metabolism • Deficient lipid metabolism • Deficient neurotransmier synthesis [serotonin, epinephrine, norepinephrine and gamma amino butyric acid (GABA)] -PLP is involved in the synthesis of sphingolipids, Its deficiency leads to demyelinaon of nerves and consequent peripheral neuris

Mild deficiency leads to: Severe deficiency leads to:

Irritability Peripheral neuropathy Nervousness Convulsions Depression -Cyanocobalamin and Hydroxycobalamin is commercially available form found as supplementary form -Adenosylcobalamin the most active Vitamin B12

Forms • Cyanocobalamin • Hydroxycobalamin • Adenosylcobalamin (major storage form in the liver) • Methylcobalamin (mostly found in blood circulaon) Coenzyme -Adenosylcobalamin and Methylcobalamin (Coenzymes for metabolic reacons) -Body can convert other cobalamins into acve coenzymes see next slide.. Sources • Mainly found in animal liver bound to protein as Ø Methylcobalamin Ø 5’-deoxyadenosylcobalamin • Not synthesized in the body and must be supplied in the

diet

Absorpon • Binds to intrinsic factor and absorbed by the ileum + • Intrinsic factor is a protein secreted by cells in the Stores stomach • Liver stores vitamin B12 (4-5 mg) • Only water soluble vitamin that is stored in the body Vitamin B12 Vitamin B12

Importance..? 1-Essenal for normal nervous system funcon and red blood cell maturaon. 2-Required in 2 reacons:

Conversion of propionyl-CoA Conversion of homocysteine to succinyl-CoA to methionine •The enzyme in this pathway, • Methionine synthase methyl-malonyl-CoA mutase, requires B12 in converng homocysteine to requires B12 methionine

Tetrahydrofolate is the active form found in the body

Vitamin B12

Homocysteine re-methylaon reacon is the only pathway where N5-methyl TH4 can be returned back to tetrahydrofolate pool..

Hence folate is trapped as è N5-methyltetrahydrofolate (folate trap)

This leads to folate deficiency and deficiency of other TH4 derivaves (N5-N10 methylene TH4 and N10 formyl TH4) required for purine and pyrimidine syntheses *TH4: Tetrahydrofolate

Interconversion between TH4 carrier of “one-carbon units”

We don’t have to memorize the structure Vitamin B12

Disorders of Vitamin B12 Deficiency

Pernicious anemia Demyelinaon Neuropathy Megaloblasc anemia Myelin sheath of Peripheral nerve Vitamin B12 deficiency is neurons is chemically mainly due to the deficiency damage of intrinsic factor unstable and damaged

break down the lipid for this myelination, and nerves will be affected. Vitamin B12

Neuropsychiatric symptoms of Vitamin B12 Deficiency..? affect both sensory and motor

Neurological symptoms Psychiatric symptoms

Paraesthesia (abnormal sensaon) of Confusion and memory loss hands and feet

Reduced percepon of vibraon and posion Depression

Unstable mood Absence of reflexes eg: babinski reflex

Unsteady gait and balance (ataxia) 4:44

Vitamins B6 B12 1. Pyridoxine 1. Cyanocobalamin 2. Pyridoxal 2. Hydroxycobalamin Forms 3. Pyridoxamine 3. Adenosylcobalamin (in liver) 4. Methylcobalamin (in blood circulation)

Acve Form Pyridoxal phosphate Adenosylcobalamin, Methylcobalamin Work as coenzyme for: 1. Conversion of Propionyl-CoA to succinyl-CoA Funcon 1. Transamination 2. Deamination 2. Conversion of Homocysteine to methionine 3. Decarboxylation 4. Condensation reactions

*Rare paents with IF* such as: Dietary • Newborn infants fed on formulas low in B6 • Autoimmunity deficiency • Women on oral contracepves • Paral or total gastrectomy observed in • Alcoholics • Isoniazid treatment for tuberculosis • Deficient amino acid metabolism • Pernicious anemia • Deficient lipid metabolism • Demyelination Deficiency • Deficient neurotransmitter synthesis • Neuropathy diseases • Demyelination of nerves and consequent peripheral neuritis Mild deficiency leads to: Neurological symptoms: Irritability, Nervousness, Depression Paraesthesia of hands and feet Reduced perception of vibration and position Severe deficiency leads to: Symptoms Absence of reflexes, ataxia. Peripheral neuropathy, Convulsions Psychiatric symptoms: Confusion, memory loss, Depression, Unstable mood 1.The acve form of vitamin B6 is: 5.Vit B12 is mainly stored in liver A.pyridoxine in the form of : B.hydroxycobalamin A. adenosylcobalamin C.pyridoxal phosphate B. methylcobalamin D.pyridoxamine C. cyanocobalamin D. phylloquinone 2.Vitamin B6 is involved in the formaon of heme by which of the following reacons ? 6.Which of the following is a A. decarboxylaon result of folate trapping ? B. condensaon A. neuropathy C. aminotransducon B. ataxia D. deaminaon C. depression D. pernicious anemia 3.Vit B6 deficiency could results in : A. bleeding 7.Accumulan of malonyl coA B. night blindness leads to : C. neural tube defects A. abnormal myelin synthesis D. anexity B. decrease intrinsic factor levels C. inability to synthesize 4.An other name of vitamin B12 : Pyrimidine A. riboflavin D. abnormal cell division B. ascorbic acid C. renol D. cobalamin

Done by: Ameera bin zuair Mada albatli Najla aldraweish Reema alrasheed Reema alhammad