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B-COMPLEX VITAMINS

Dr. M. Siva Kumar Reddy MBBS.,MDPost graduateDepartment of biochemistry

CLASSIFICATION

WSV vs FSVWater soluble vitaminsFat soluble vitaminsFunction as Precursor for co-enzymes & anti oxidantsFunction as co-enzymes , harmones, and anti-oxidantsExcess amounts non toxicExcess amounts are toxicThese vitamins are not stored except B12These vitamins are storedBody requires them frequentlyThey are not required frequently

B- COMPLEX VITAMINSB1- THIAMINEB2-RIBOFLAVINB3-NIACINB5-PANTOTHENIC ACIDB6-PYRIDOXINEBIOTINFOLIC ACIDB12-CYANOCOBALAMINE

THIAMINE B1

You should at least know these.Specific co-enzyme of thiamine?Dietary sources of thiamine?Antimetabolites of thiamine?RDA of thiamineTypes of beri beri & most complicated form of beri beriMetabolic reactions where TPP is involvedMost commonly effected people?Investigations and treatment?

OTHER NAMES OF THIAMINEAnuerineThiaminThio-vitamineAnti beriberi factorSulphur containing vitamine

HISTORY OF THIAMINE

KANEHIRO TAKAKI

SURGEON GENERAL IN JAPANESE NAVY

found seamen and crew were effected

CHRISTIAN EIJKMAN

Dutch physician and professor of physiology

nobel prize winner accidentally found the cause in fowls fed with cooked rice

Structure of thiamine

ADOLF OTTOWINDAUSNP 1928

THIAMINE PYROPHOSPHATE(SPECIFIC CO-ENZYME)

Glucose Glucose 6 PPyruvateAcetyl CoATPPPDHTCATPPCitrateOxaloacetate- Ketoglutarate- Ketoglutarate dehydrogenaseSuccinyl CoARibose - 5PTransketolaseTPPSeduheptulose - 7PXylulose - 5PGlyceraldehyde - 3P

Pyruvate Acetyl - CoANAD+ NADH+H+

Lipoate, CoA-SH, FADCO2

Oxidative decarboxylationVitamin B1 - ThiamineTPPPDH

ketoglutarate Succinyl - CoANAD+ NADH+H+

Lipoate, CoA-SH, FADCO2

Oxidative decarboxylationVitamin B1 - ThiamineTPP

Vitamin B1 - Thiamine

Xylose-5 phosphateRibose-5 phosphateGlyceraldehyde-3 phosphateSedoheptulose-7 phosphate

Transketolase TPP

And also..Essential for transmission of nerve impulse

TPP is required for synthesis of Acetylcholine.

DUE TO LACK OF TPPIncreased plasma levels of pyruvate & lactate due to low activity of PDH complexAccumilation of pentose sugars in erythrocytes is due to decreased activity of transketolaseMeasurement of Transketolase activity is common test used for the diagnosis of B1 deficiency

Sources of thiamine

Thiaminase It is present in raw fish & seafoodThiaminase destroys thiamine if it is present in the dietANTIMETABOLITES

ABSORBTION: Thiamine is carried by the portal blood to the liver, present as free thiamine STORAGE: Usually stored as thiamine pyrophosphateMainly stored in skeletal muscle and also present in significant amounts in liver, heart, kidneys, erythrocytes and nervous system

RDAAdults - 1-1.5 mg/dayChildren - 0.7-1.2 mg/dayPregnancy & lactation - 2 mg/day

REQUIREMENT INCREASES WITH- increased carbohydrate intakePregnancyLactationSmokingAlcoholismProlonged antibiotic intakeSerious or prolonged illness

Food containing a high level of thiaminase, including milled rice, raw freshwater fish, raw shellfish, and fernsLack of thiamine intakeFood high in anti-thiamine factor, such as tea, coffee, and betel nutsProcessed food with a content high in sulfite, which destroys thiamineAlcoholic stateStarvation state

Causes of thiamine deficiency

Increased depletionDiarrheaDiuretic therapiesPeritoneal dialysisHemodialysisHyperemesis gravidarum

Decreased absorptionChronic intestinal diseaseAlcoholismMalnutritionGastric bypass surgeryMal absorption syndrome - Celiac and tropical sprue

Increased consumption statesDiets high in carbohydrate or saturated fat intakePregnancyHyperthyroidism LactationFever - severe infectionIncreased physical exercise

Thiamine Deficiency:Vitamin B1 - Thiamine

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BERI BERI CLASSIFICATION Dry BeriberiWet BeriberiInfantile BeriberiShoshin BeriberiWernicke-Korsakoff syndrome

INVESTIGATIONSerythrocyte Transketolase activity and 24-h urinary thiamine excretion may be measured.Need to rule out other causes.

TREATMENTSupplement thiamine, with dose based on clinical manifestationsFor mild polyneuropathy, thiamine 10 to 20 mg once/day is given for 2 wk. For moderate or advanced neuropathy, the dose is 20 to 30 mg/day; it should be continued for several weeks after symptoms disappear. For edema and congestion due to cardiovascular beriberi, thiamine 100 mg IV once/day is given for several days.

The prognosis for beriberi is usually good, unless patients have established Korsakoff syndrome. When patients have progressed to this stage, the degree of damage is only minimally reversible.

PROGNOSIS OF BERIBERI

RIBOFLAVINVITAMIN- B2

You should at least know these.Specific co-enzyme of Riboflavin?Dietary sources of Riboflavin?RDA of Riboflavin?Riboflavin deficiency clinical features?Metabolic reactions where FAD and FMN are involved?Most commonly effected people?Investigations and treatment?

OTTO HEINRICH WARBURG

Isolated the "yellow enzyme of cellular respiration.

He was nominated 47 times for Nobel prize

Known for his works in cancers

AXEL THEORELL

Isolated riboflavin

Won Nobel prize in 1955 for his discovery of oxidation enzymes and its effects

PAUL KARRER Determined the structure of riboflavin

Best known for his research in vitamins

Won Nobel prize in 1937

Riboflavin - CHEMISTRY

It contains heterocyclic isoalloxazine ring and ribitol a sugar alcohol

It is sensitive to light.

Riboflavin - SOURCES

SourcesMilkCheeseEggsMeat Yeast extractsGreen vegetables38

In the United States today, the most significant dietary sources of riboflavin are meat andmeat products, including poultry and fish, and milk and dairy products, such as eggs andcheese. In developing countries, plant sources contribute most of the dietary riboflavinintake. Green vegetables, such as broccoli, collard greens, and turnip greens, are reasonablygood sources of riboflavin. Natural grain products tend to be relatively low in riboflavin,but fortification and enrichment of grains and cereals has led to a great increase inriboflavin intake from these food items.The food sources of riboflavin are similar to those of other B vitamins. Therefore,it is not surprising that if a given individuals diet has inadequate amounts of riboflavin,it will very likely be inadequate in other vitamins as well. A primary deficiency of dietaryriboflavin has wide implications for other vitamins, as flavin coenzymes are involved inthe metabolism of folic acid, pyridoxine, vitamin K, niacin, and vitamin D (27). from dietary sources. Appreciable amounts of riboflavinmay be lost with exposure to UV light, particularly during cooking and processing.Prolonged storage of milk in clear bottles or containers may result in flavin degradation(28). Fortunately, most milk is no longer sold in clear bottles. There has been some controversyas to whether opaque plastic containers provide greater protection than do cartons,particularly when milk is stored on a grocery shelf exposed to continuous fluorescentlighting.38

Vitamin B2 -RiboflavinAbsorption and Transport

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Vitamin B2 -RiboflavinRDA

1.3 1.7mg/day

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Riboflavin ACTIVE FORMS

FMN is formed in intestineFAD is formed in LiverFlavin dependent enzymes (flavoproteins)41

Riboflavin ACTIVE FORMS

Riboflavin ACTIVE FORMSActive forms of this vitamins(FMN & FAD) are involved inCarbohydrate metabolism(PDH &TCA)Lipid metabolismProtein metabolismPurine metabolism

Vitamin B2 -RiboflavinFunctions

The major function of riboflavin, as noted above, is to serve as the precursor of the flavincoenzymes, FMN and FAD, and of covalently bound flavins. These coenzymes are widelydistributed in intermediary metabolism and catalyze numerous oxidationreduction reactions.Because FAD is part of the respiratory chain, riboflavin is central to energy production.Other major functions of riboflavin include drug and steroid metabolism, inconjunction with the cytochrome P450 enzymes, and lipid metabolism. The redox functionsof flavin coenzymes include both one-electron transfers and two-electron transfersfrom substrate to the flavin coenzyme (10).Flavoproteins catalyze dehydrogenation reactions as well as hydroxylations, oxidativedecarboxylations, dioxygenations, and reductions of oxygen to hydrogen peroxide.Thus, many different kinds of oxidative and reductive reactions are catalyzed by flavoproteins.44

Vitamin B2 -Riboflavin

FMN Dependent enzymes:FMN is a cofactor for L- amino acid oxidase.NADH dehydrogenase of respiratory chain contains FMNFAD Dependent enzymes:D-amino oxidaseSuccinate dehydrogenaseAceyl coA dehydrogenaseXanthine oxidasePyruvate dehydrogenaseA ketoglutarate dehydrogenaseComplex II of R chain45

coenzymes for oxidoreductase enzymes(FAD and FMN)Flavoprotien enzymePathway/ reactionAmino acid oxidaseDeamination of amino acidsXanthine oxidasePurine degradationSuccinate dehydrogenaseCitric acid cycleAcyl-coA dehydrogenaseFatty acid oxidationNADH dehydrogenaseRespiratory chain in mitochondriaPyruvate dehydrogenase and Alpha keto glutarateOxidative decarboxylation of pyruvate and alpha ketoglutarate

Riboflavin - DEFICIENCY

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CONEAL VASCULARISATION

INVESTIGATIONSUrinary riboflavin determinationRBC riboflavin load test

TREATMENTRiboflavin 2-5 mg PO daily with incresed intake of B-complex vitaminsParenteral riboflavin administered if relief not obtained with oral intake.

ReferencesHarpers Biochemistry 25th Edition.Fundamentals of Clinical Chemistry by Tietz. Text Book of Medical Biochemistry-A R Aroor.Text Book of Biochemistry- DM VasudevanText Book of Biochemistry-MN ChatterjeaText Book of Biochemistry-Dr.U.Satyanarana