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 quan88es in different types of food -Important for growth and good health -Help in various biochemical processes in cell -Func8on as coenzymes Energy-releasing Hematopoie>c 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 Ac>ve form..? reac8ons: All 3 are converted to pyridoxal phosphate (PLP) 90% in muscles. (next slide) 1. Condensa>on Reac>on. 2. Decarboxyla>on Reac>on: 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. Transamina>on Reac>on. 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 deriva:ve with PLP. Deficiency leads to..? -Poor ac8vity of PLP-dependent enzymes Causing: • Deficient amino acid metabolism • Deficient lipid metabolism • Deficient neurotransmiYer 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 neuri8s 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 reac8ons) -Body can convert other cobalamins into ac8ve 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 Absorp>on • 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-Essen8al for normal nervous system func8on and red blood cell maturaon. 2-Required in 2 reac8ons: 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 Megaloblas>c 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 percep8on 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) Ac>ve Form Pyridoxal phosphate Adenosylcobalamin, Methylcobalamin Work as coenzyme for: 1. Conversion of Propionyl-CoA to succinyl-CoA Func>on 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 contracep8ves • Par8al 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 ac>ve 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. aminotransduc8on B. ataxia D. deaminaon C. depression D. pernicious anemia 3.Vit B6 deficiency could results in : A. bleeding 7.Accumula>n 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 .