3 water-soluble Vitamins; Vitamins : arechemically unrelated organic compoundscannot be synthesized by humansmust be supplied by the diet.water-soluble Vitamins;folic acid cobalamin (B12)ascorbic acid (C) pyridoxine (B6)Thiamine (B1) niacin (B3)Riboflavin (B2) biotinpantothenic acidMany of the water-soluble vitamins are precursors of coenzymes for the enzymes of intermediary metabolism.
4 FOLIC ACID (Folate) Function of Folic acid Plays a key role in one-carbon metabolism.Essential for the biosynthesis of AA, purines, thymine...etc.Folic acid deficiency is the most common vitamin deficiency in the United States, particularly among pregnant women and alcoholics.Function of Folic acidSerine, glycine, and histidine one-carbon fragments to Tetrahydrofolate transfers them to intermediates in the synthesis of amino acids, purines, and thymine - a pyrimidine found in DNA.
5 Nutritional anemias Low blood [Hb] O2 transport Anemia Nutritional anemias : classifiedaccording to RBC size or MCV.Microcytic anemia (MCV<80 m3):caused by lack of ironthe most common form of nutritional anemia.b) Macrocytic anemias (MCV>100 m3):due to folic acid or vit B12 def.called megaloblastic because folic acid or vit B12 def. accumulation of large, immature red cell precursors(megaloblasts) in the bone marrow.
7 Folate and anemia: poor absorption: pathology of gut Causes of serum increased demand:PregnancyLactationpoor absorption:pathology of gutAlcoholismttt with : Methotrexate(DHF reductase inhibitor)Causes of serumfolate levelsfolate-free dietResults offolic acid deficiencymegaloblastic anemia due to synthesis of purines and thymidine DNA synthesis and cell division.The causes of the megaloblastic anemia should be evaluated prior to instituting therapy because vitamin B12 deficiency indirectly causes this disorder.
9 Folate and neural tube defects in the fetus: Spina bifida and anencephaly, the most common neural tube defects.affect ~ 4000 pregnancies in USA / year.Folic acid supplementation before conception and during the first trimester ( 0.4 mg/day) the risk of neural tube defects in the fetus.The U.S. FDA has authorized the addition of folic acid to enriched grain products, ( about 0.1 mg day).This supplementation will allow ~ 50% of all reproductive-aged women to receive 0.4 mg of folate from all sources.Folic acid intake should not exceed ~ 1 mg/day to avoid misdiagnosis of vit B12 deficiency.
10 COBALAMIN (VITAMIN B12)Required in humans for 2 essential enzymatic reactions:A) Methionine synthesisB) isomerization of methylmalonyl CoA (produced during the degradation of some AA, and fatty acids with odd numbers of carbon atoms)Deficiency of B12 accumulation of abnormal fatty acids incorporated into cell membranes, including nervous system neurologic manifestations .
11 A. Structure of cobalamin and its coenzyme forms Coordinationbondscyanide is replaced by CH3 groupcyanide is replaced with 5-deoxyadenosinediffers from the porphyrins in that two of the pyrrole rings are linked directly rather than through a CH3 bridgeCobalt is held in the center of the corrin ring by four coordination bonds from the nitrogens of the pyrrole groups
12 Distribution of vit B12 :Vitamin B12 is synthesized only by microorganisms.It is not present in plants.Animals obtain the vitamin preformed from:their natural bacterial flora.by eating foods derived from other animals.liverwhole milkeggsoystersfresh shrimpchickenB12 is present in:
13 Folate trap hypothesis : B12 deficiency affects:need both N5-N10-methylene & N10- formyl forms of THF for nucleotides synthesis required for DNA replication.the erythropoietic tissue of bone marrowthe mucosal cells of the intestineIn B12 deficiency, the N3-methyl form of tetrahydrofolate is not efficiently used.Methylated form of THF cannot be converted directly to other forms accumulation of he N5-methyl form & of other forms.B12 deficiency is hypothesized to deficiency of the THF forms needed in purine and thymine synthesis, megaloblastic anemia.
14 Clinical indications for vitamin B12 Unlike other water-sol Vitamins, significant amounts of vitamin B12 (4 - 5 mg) are stored in the body.SO,Development of clinical symptoms of B12 deficiency take several years in individuals with partial or total gastrectomy (intrinsic factor-deficient with loss of B12 absorption).
15 Pernicious anemia:Vitamin B12 deficiency is rarely due to dietary insufficiency.Deficiencies are more common in patients with intestinal malabsorption of the vitamin pernicious anemia.Autoimmune destruction of the gastric parietal cells synthesis of the intrinsic factor (Glycoprotein).Normally, dietary vitamin B12 binds to intrinsic factor in the intestine cobalamin - intrinsic factor complex travels through the gut binds to specific receptors on the surface of mucosal cells of the ileum transported into the mucosal cell general circulation carried by B12-binding proteins.
16 Neuropsychiatric symptoms develops later . Lack of intrinsic factor prevents vitamin B12 absorption pernicious anemia.Neuropsychiatric symptoms develops later .CNS symptoms may occur in the absence of anemia.The CNS effects are irreversible.Treatmentby giving high-dose B12 orally, or cyanocobalamin IM.Therapy must be continued throughout the lives of patients with pernicious anemia.Folic acid administration alone reverses the hematologic abnormality masks the B12 deficiency severe neurologic dysfunction and pathology;therefore, megaloblastic anemia should be treated with a combination of folate and vitamin B12
17 ASCORBIC ACID (VITAMIN C) The active form of vitamin C is ascorbic acid.The main function is as a reducing agent in several different reactions.Vitamin C has an essential role as a coenzyme in hydroxylation reactions, e.g, hydroxylation of prolyl- and lysyl-residues of collagen .Vitamin C is required for:maintenance of normal connective tissuewound healingfacilitates the absorption of dietary iron from the intestine.
18 Deficiency of ascorbic acid: Deficiency of ascorbic acid deficiency in the hydroxylation of collagen defective connective tissue scurvy.sorespongy gumsloose teethfragile blood vesselsswollen jointsanemiaScurvy
19 Prevention of chronic disease: Vitamin C , vitamin E and -carotene are known as antioxidants.Consumption of food or supplements rich in these compounds Coronary heart disease and certain cancers.Supplementation with the isolated antioxidants have low beneficial effects.
20 PYRIDOXINE (VITAMIN B6) pyridoxalpyridoxamine,Derivativesof pyridine.They differ only in the nature of the functional group attached to the ringin animal foodsAll three compounds can serve as precursors of the biologically active coenzyme, pyridoxal phosphate.Pyridoxal phosphate functions as a coenzyme catalyze reactions involving amino acidsprimarily in plants
22 Clinical indications for pyridoxine: Isoniazid (isonicotinic acid hydrazide), [a drug frequently used to treat TB] B6 deficiency by forming an inactive derivative with pyridoxal phosphate.Dietary supplementation with B6 is important with isoniazide treatment.Dietary deficiencies in pyridoxine are rare but observed in:newborn infants fed formulas low in vitamin B6women taking oral contraceptivesalcoholics.intakes of greater than 2 g/day Neurologic symptomsToxicity of pyridoxine:Substantial improvement, but not complete recovery, occurs when the vitamin is discontinued
23 THIAMINE (VITAMIN B1) Thiamine pyrophosphate (TPP) is: the biologically active form of the vitamin,formed by the transfer of a pyrophosphate group from ATP to thiaminePP from ATP
24 Clinical indications for thiamine: Thiamine pyrophosphate (TPP) serves as a coenzyme in :the formation or degradation ofα-ketols by transketolasethe oxidative decarboxylationof pyruvate and α -keto acidsImportant for CNSThiamine deficiency: activity of dehydrogenase reactions ATP impaired cellular function.Thiamine deficiency is diagnosed by: erythrocyte transketolase activity observed on addition of TPP.
25 Beri beri: Severe thiamine-deficiency syndrome. Found in areas where polished rice is the major component of the diet.Rapid onset in nursing infants whose mothers are deficient in thiamine.infantile beriberiAdult beriberitachycardiavomitingconvulsionsdeath (if untreated)dry skinirritabilitydisorderly thinkingprogressive paralysis
26 Wernicke-Korsakoff syndrome: In the United States, thiamine deficiency, which is seen primarily with chronic alcoholism, is due to:dietary insufficiency.impaired intestinal absorption of the vitamin.Some alcoholicsWernicke - Korsakoffsyndrome- apathy,- loss of memory- rhythmical to-and-fro motion of the eyeballs
27 Niacin, or nicotinic acid, is a substituted pyridine derivative The biologically active coenzyme forms are:nicotinamide adenine dinucleotide (NAD) and its phosphorylated derivative,nicotinamide adenine dinucleotide phosphate (NADP)Nicotinamide, a derivative of nicotinic acid that contains an amide instead of a carboxyl group, deaminated in the body So it is nutritionally equivalent to nicotinic acid.
28 NAD+ and NADP+ serve as coenzymes in oxidation-reduction reactions in which the coenzyme undergoes reduction of the pyridine ring by accepting a hydride ion (hydrogen atom plus one electron)The reduced forms:NAD+ NADHNADP+ NADPH
29 A. Distribution of niacin Sourcesunrefined and enriched grains and cerealsmilklean meats especially liver.Limited quantities of niacin can also be obtained from metabolism of tryptophan.60 mg tryptophan 1 mg nicotinic acidtryptophan is metabolized to niacin only when there is a relative abundance of the amino acid
30 B. Clinical indications for niacin : Deficiency of niacinPellagraif untreatedDermatitisDiarrheaDementiaDeath
31 Treatment of hyperlipidemia: Niacin(at doses of 1.5 g /day or 100 times the RDA)inhibits lipolysis in adipose tissue( the primary producer of circulating free fatty acids). triacylglycerol synthesis in liver VLDL and LDLNiacin is particularly useful in the treatment of type lIb hyperlipoproteinemia (in which VLDL & LDL ).
32 RIBOFLAVIN (VITAMIN B2) (FMN)(FAD)FMN & FAD are: the 2 biologically active forms. formed by transfer of AMP from ATP FMN. capable of reversibly accepting 2 H atoms FMNH2 or FADH2 bound tightly - sometimes covalently - to flavoenzymes that catalyze the oxidation or reduction of a substrate.dermatitischeilosis (fissuring at the corners of the mouth),glossitis (the tongue appearing smooth & purplish).Deficiency
33 BIOTINA coenzyme in carboxylation reactions, ( serves as a carrier of activated CO2 ).Covalently bound to the -amino groups of lysine residues of biotin-dependent enzymes.Required by all organisms.Can only be synthesized by: bacteria, yeasts, molds, algae, and some plant species.
34 Each Carboxylase catalyzes an essential metabolic reaction: Acetyl-CoA carboxylase:catalyzes the binding of HCO3- to acetyl-CoA to form malonyl-CoA required for the synthesis of fatty acids.Pyruvate carboxylase:in gluconeogenesis formation of glucose from amino acids and fats.Each Carboxylase catalyzes an essential metabolic reaction:Methylorotonyl-CoA carboxylase:in the metabolism of leucine, an essential amino acid.Propionyl-CoA carboxylase:in the metabolism of amino acids, cholesterol, and odd chain fatty acids (fatty acids with an odd number of carbon molecules)
35 Biotin deficiency very rare. does not occur naturally. the vitamin is widely distributed in food.in humans, big percentage is supplied by intestinal bacteria.Biotin deficiencyprolonged IV feeding without biotin supplementation.consumption of raw egg white for a prolonged period .Human requirementfor dietary biotin in:
36 symptoms of biotin deficiency dermatitisglossitisloss of appetiteloss of hairnauseascaly red rash around the eyes, nose, mouth, and genital area.Addition ofraw egg-whiteto the dietas a sourceof proteinsymptomsof biotindeficiencydepressionlethargyhallucinationnumbnesstingling of extremities.Neurologicsymptomsin adultsRaw egg white contains a glycoprotein, avidin tightly binds biotin prevents its absorption from the intestine.Cooking egg white denatures avidin renders it digestable unable to prevent the absorption of dietary biotin.
37 With a normal diet, 20 raw eggs / day would be required to induce a deficiency syndrome. The Adequate Intake (AI): average intakes of biotin (35 mcg to 60 mcg/day) are meeting the dietary requirement.Uses:In larger doses, biotin is used to treat inborn errors of metabolism such as biotinidase deficiency.Biotin is incorporated into almost all nutritionally complete dietary supplements and infant formulas.
38 Pantothenic acid is also a component of fatty acid synthase . A component of coenzyme A, which functions in the transfer of acyl groupsCoenzyme A contains a thiol group that carries acyl compounds as activated thiol esters.such structures are succinyl CoA, fatty acyl C0A, and acetyl CoA.Sources:EggsLiverYeastDeficiencyIs not well characterizedin humans,No RDA is established.Pantothenic acid is also a component of fatty acid synthase .