Vitamin Defined
‘An organic substance that occurs in foods in
small amounts and is necessary for normal
metabolic function...
Essential Vitamins For Human Being
vitamins
water -soluble lipid-soluble
Vit C Vit B A,D,E,K
B1, B2, B6, B12, PP, patothen...
Overview of Water Soluble Vitamins
Heterogeneous( differ chemically)
Dissolve in water
Readily excreted through urine
...
• The water soluble vitamins form coenzymes
(active form of the vitamin).
Co-enzyme
Co-enzyme
Thiamine- Vitamin B-1
• “thio”-vitamin (sulfur-containing vitamin)
• Ist vitamin to be identified
• Other names
– Anti neu...
• Relatively unstable
-Destroyed with heat and in alkaline environment
-Lost by milling flour, leaching into cooking liqui...
Thiamine
Sources
 Pork, hot dogs &
luncheon meat
 Cold cereals
 Sunflower seeds
 Green beans
 Whole/Enriched
Grains
RDA and Toxicity
• 1to 1.5 mg/day
• Requirement increases in pregnancy &
lactation(2mg), old age & alcoholism.
• Daily int...
Pyrimidine
Thiazole
The Active Form
• Thiamine contains an aminopyrimidine
ring and a thiazole ring.
• Active forms - Thia...
Biochemical Functions
Needed for the metabolism of
carbohydrates, proteins and fats
Thiamine pyrophosphate (TPP) is
involv...
Oxidative Decarboxylation
reactions
 Pyruvate Dehydrogenase (PDH)
 α Ketoglutarate Dehydrogenase.
Transketolation reacti...
The branched chain aminoacid dehydrogenase
(decarboxylase)
 Leucine, isoleucine , valine to form keto acid.
Pts of Maple ...
Absorption, Transport & Metabolism
• Absorbed in the upper small intestine
– Low concentration = carrier mediated
– High c...
Thiamine Deficiency
Causes:
• Inadequate Diet (polished rice)
• Alcoholism
• chronic illness(liver cirrhoses,
disease affe...
Deficiency
Women with hyperemesis
gravidarum and anorexia
• Pt on parental glucose
• Pt on chronic diurectic therapy
• Mat...
Thiamine Deficiency
Biochemical Changes:
 Carbohydrate metabolism is impaired.acc of pyruvate in
tissues
 Increased pyru...
Clinical manifestations
Deficiency leads to Beri-beri which is of three types.
 Wet Beri-beri: CVS manifestations are pro...
Clinical manifestations
 Dry Beri-beri: CNS manifestations prominent.
 Edema not commonly seen.
 Neurological manifesta...
Clinical manifestations
Wernicke-Korsakoff syndrome: Seen in chronic
alcoholics and is characterized by:
 Loss of memory...
Lab diagnosis
Lack of nerve impulse transmission
RBC transketolase activity is dec, its
measurement is diagnostic This i...
Therapeutic Use
• 1 . Prophylactically (2-10 mg daily) in infants,pregnant women,
chronic diarrhoeas, patients on parenter...
4. In neurological and cardiovascular disorders, hyperemesis
gravidarum, chronic anorexia and obstinate constipation-
thia...
Riboflavin (Vit. B2)
• The name "riboflavin" comes from “ribose” and “flavin”
• Coenzymes:
– Flavin mononucleotide (FMN)
–...
Riboflavin
Sources
• Milk/products
– Yogurt, Cheese
• Meat & eggs
• Liver
• Enriched /whole grains
• Oyster
• Brewer’s yea...
Absorption, Transport, & Metabolism
• HCL in the stomach releases riboflavin from its
bound form
• Absorption
– Active or ...
Active Coenzymes of Riboflavin
• FMN: Flavin mononucleotide:
Formed in the intestine by phosphorylation of Riboflavin in t...
Functions
•Growth promoting factor:
–Repair & development of body tissues - healthy skin
•Act as “coenzymes” in many react...
Who is at Risk For Deficiency?
 Rare, usually with other vit b deficiency
 Low milk/dairy intake
Gastrointestinal disea...
Deficiency
• Ariboflavinosis:
– Glossitis, cheilosis & angular stomatitis
– Sore & raw tongue
– seborrheic dermatitis
– Lo...
• Deficiency can be seen in anorexia , malabsorbtion.
• Drugs eg. Barbiturates (microsomal oxidation of
vitamin)
• Symptom...
Lab Diagnosis
• Lab measurement of RBC and urinary riboflavin
• Measurement of erythrocyte glutathoine reductase
activity ...
Niacin (Vit. B3)
• 2 Forms
– Nicotinic acid (niacin)
– Nicotinamide (niacinamide)
• Coenzyme (liver)
– Nicotinamide adenin...
Niacin
Sources
• All protein foods
• Milk, eggs, meat, fish,
poultry
• Whole/Enriched
grains
• Nuts, Mushrooms
• Can be sy...
Absorption and Metabolism
• Absorbed in the upper part of the small
intestine
• It is stored only sparingly in the kidney,...
RDA
Adult 15-20mg/d children 10-15mg/d
Niacin equivalent = 1mg niacin= 60mg tryptophan
ma ize eaters have suffered from pe...
acid.
3. Hartnup's disease: in which tryptophan
transport is impaired, and in carcinoid tumours
which use up tryptophan fo...
• The oxidation–reduction reactions catalyzed by enzymes
belonging to ‘oxido-reductases’
• α- ketoglutarate Succinyl CoA
N...
Glucose-6P 6-phospho-gluconolactone
NADP+
NADPH + H+
PentosePhosphate
pathway
• The Oxidative-Phosphorylation: NADH that i...
Functions
 NADPH is important in Reductive Anabolic Pathways
(Reductive Biosynthesis) by donating reducing equivalents
(N...
Function
• . Flavoproteins regenerate them by
oxidizing N ADH and NADPH.
• Nicotinic acid (but not nicotinamide) in
large ...
 Pellagra [3 D’s]
– Dermatitis
• scaly dermatitis
• sun exposed surfaces of skin
• starts as red pigmentation which turn ...
Deficiency
• Pellagra – characterized as the disease
causing 4D’s
– Dermatitis
– Diarrhea
– Depression
– Death
Symptoms
• Weakness
• Persistent fatigability
• Irritability
• Headache
• Depression
• Soreness and inflammation of the to...
Laboratory assessment
• Urinary excretion of niacin
metabolites
 N-methyl nicotinamide
 2-pyridone
Causes of Deficiency
 Vitamin B6 deficiency
 Isoniazid:
 Hartnup Disease: Tryptophan absorption from intestine is
defec...
Niacin as a Medicine
• Inhibits lipolysis in adipose tissues
• 75-100 x RDA can lower LDL and TG and increase HDL
• Slow/ ...
Pantothenic Acid
• Vitamin B-5
• Its name derives from the Greek word pantothen meaning
"from everywhere“.
• Easily destro...
Pantothenic acid
Sources
• Widespread in foods
• Meat, Liver
• Milk
• Mushrooms
• Avacado
• Peanuts
• Broccoli
• Whole gra...
Structure:
•Pantothenic acid contains β alanine and pantoic acid.
•The active Coenzyme A (CoA) differs according to the
gr...
Biochemical functions
Acetyl CoA
 TCA cycle
 Acetyl choline synthesis (neurotransmitter)
 Fatty acid metabolism
Succi...
Deficiency
• Rare
• Usually in combination with other deficiencies
• Signs/symptoms
 Irritability, fatigue & apathy
 Neu...
Biotin
• Vitamin B-7 & Vitamin H
• Anti Egg White Injury Factor: Avidin, a protein found in raw
egg white, inhibits the ab...
Biotin
Sources:
• Organ meats, fish
• Egg yolks
• Soybeans
• Whole grains
• Cheese
• Peanuts
• Also produced by GI
bacteri...
Active form of Biotin acts as coenzyme for Carboxylation
reactions (addition of carbon in the form of CO2).
Examples:
Ca...
Signs/symptoms:
 Hair loss (alopecia)
 Depression, lethargy, hallucinations, numbness and
tingling of the extremities
...
Vitamin B-6
 Various forms: [pyridine derivatives]
– Pyridoxine
– Pyridoxal
– Pyridoxamine
 Pyridoxal phosphate [PLP]
– ...
Vitamin B6
Sources
• Meat, fish, poultry, liver
• Potatoes, Legumes
• Banana
• Spinach
• Avocado
• Whole grains
• Soy prod...
Absorption, Transport & Metabolism
• Absorbed passively
• Binds to albumin for transport in the blood
• B-6 is stored in t...
Functions
• Amino acid metabolism
Transamination
Deamination
Decarboxylation (Histamine synthesis)
Condensation (Haemo...
Deficiency
 Microcytic hypochromic anemia
 Seborrhoeic dermatitis
 Atrophic glossitis with ulceration
 Angular cheilit...
B-6 As A Medicine
• Morning sickness in early pregnancy
• PMS
• Mental depression
• Cut the risk of parkinson’s disease by...
Folic acid
• From the Latin word “folium” (which means “leaf”)
• Other names
Folacin
Vitamin B-9, Vitamin M & Vitamin Bc...
Folic acid
Sources
• Leafy Green
Vegetables
• Fortified Grains
• Legumes, Seeds
• Liver
RDA
• 400 ug/day for
adults
Absorption, Transport & Metabolism
• Absorbed in the monoglutamate form with help of folate
conjugase
– Active absorption ...
Functions
• Synthesis, repair & methylation of DNA
– Transfer of single carbon units
– Synthesis of amino acids, purines &...
Deficiency
 Sign/symptoms
– Anemia (megaloblastic)
– Neural tube defects (in developing embryo)
– Peripheral neuropathy
–...
Megaloblastic Anemia
Toxicity
• Risk is low
• Upper limit
 1 mg/day – adult men & women
 0.8 mg/day – women < 18 yrs of age
• Signs
 Epileps...
Vitamin B-12
• Also known as cobalamin
• contains cobalt
• Consists of a class of chemically-related compounds
(vitamers)
...
Vitamin B12
Sources:
• Animal products
– Meat, poultry, fish,
shellfish
– Milk, cheese
– Eggs
• Fortified cereals
RDA:
• 3...
Absorption & Metabolism
Functions
 Citric acid cycle
 Nerve functions
 Maintains myelin sheath
 Folic acid metabolism
 RBC formation & preven...
Deficiency
 Megaloblastic anemia
– Delayed or failure of normal cell division due to impaired DNA
synthesis
Pernicious a...
Vitamin C
• Vitamers of vitamin C
– Ascorbic acid (reduced form)
– Salts of ascorbic acid
• Vitamin C is purely the L-enan...
Vitamin C
Sources
– Citrus fruits
– Potatoes
– Green peppers
– Cauliflower
– Broccoli
– Strawberries
– Lettuce & spinach
Functions
 Reducing agent (antioxidant)
 Boost Immunity
 Iron absorption
 Collagen synthesis
 Healthy blood vessels
...
Collagen Synthesis
Deficiency
 Scurvy
Early symptoms
 Malaise & lethargy
After 1-3 months
 Easy bruising & petechiae
 Bleeding gums & l...
Toxicity
Adverse effects (doses > 2 gms/day):
• Indigestion & diarrhea
• Iron poisoning (in people with iron overload dis...
Thank You
A presentation by
Akif Ahsan
metabolic role and therapeutic use of b complex vitamins
metabolic role and therapeutic use of b complex vitamins
metabolic role and therapeutic use of b complex vitamins
Upcoming SlideShare
Loading in …5
×

metabolic role and therapeutic use of b complex vitamins

2,629
-1

Published on

metabolic role and therapeutic use of b complex vitamins

Published in: Health & Medicine
0 Comments
1 Like
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total Views
2,629
On Slideshare
0
From Embeds
0
Number of Embeds
0
Actions
Shares
0
Downloads
182
Comments
0
Likes
1
Embeds 0
No embeds

No notes for slide
  • differ chemically…….. Generally deficiencies due to water soluble vitamins are multiple rather than individual with overlapping symptoms. Cooking….as well as milling losses…..so the grains/cereal products are deliberately enriched with vitamins [ B-1,2,3…FA…Iron ] energy generation or hematopoises
  • Coenzyme: Small organic molecule that associates closely with enzyme functions.
  • First named  aneurin  for the detrimental neurological effects if not present in the diet..............Animals must obtain it from their diet critical role in the energy metabolism…………………….. helps orchestrate  nerve impulses  and movement in muscles as a result.
  • Most exceed RDA in diet Surplus is rapidly lost in urine; non toxic
  • RDA 1
  • (TPP) is formed when the OH group of thiamine reacts with two phosphates (pyrophosphates) donated by ATP.
  • Needed for the metabolism of carbohydrates, proteins and fats
  • Transketolase in Pentose Phosphate Pathway of glucose metabolism……… used to transform:
  • Thiamine triphosphate
  • Approximately 90% of total thiamine in blood is in  erythrocytes synthesized by colonic bacteria but this does not become available to the host. It is combine with phosphate within mucosal cells of the intestine and transported via the portal vein into the general circulation Maybe found in liver, heart, brain and muscle tissue
  • Thiamine is present in the outer layer of rice grains ….. Increase carbohydrate intake…( more requirement of thiamine). . 1) interfere with absorbtion 2)in TPP synthesis In parboiled &amp; milled rice , thiamine is not lost with polishing. Thiaminase containing diet :tea, coffee, raw fish and shell fish destroy it
  • Decreased transketolase activity………This is the earliest indicator and reliable diagnostic test to assess thiamine deficiency. Carbohydrate metabolism is impaired.acc of pyruvate in tissues is harmful Inc in plasma and urine pyruvate Inc BBBpermitting the pyruvate to enter brain directly-polyneuritis Lack of nerve impulse transmission RBC transketolase activity is dec, its measurement is diagnostic HPLC measures thiamine and its phosphorylated esters in serum or blood is measured
  • EarlierNonspecific symptoms Increased sensitivity of the oral mucosa, burning tongue, and loss or diminution of taste
  • Edema does not occur :nerve degeneration, Peripheral w eakness infantile Characterized by dyspnea, cyanosis and cardiac failure
  • in chronic alcoholics in whom the body’s demand for thiamine increases
  • Stored in paper, opaque plastic containers Ribose ….. the sugar whose reduced form, ribitol, forms part of its structure……. flavin…. the ring-moiety which imparts the yellow color to the oxidized molecule
  • Milk and milk products, meat, eggs, liver are rich sources. Cereals, fruits, vegetables and fish are moderate sources Average intake is above RDA but toxicity not documented
  • synthesized by colonic bacteria but this does not become available to the host. It must be phosphorylated (combined with phosphate) in the intestinal tract before it can be absorbed
  • The principal growth promoting factor in the vitamin B complex in the many chemical reactions involved in the m etabolism of carbohydrates, proteins and fats , including; oxidation-reduction reactions and electron transport chain .
  • Because of wide distribution (many sources), dietary deficiency is not common Gastrointestinal disease that causes vomiting and hypermotility of the gastrointestinal tract Lab measurement of RBC and urinary riboflavin, erythrocyte glutathoine reductase deficiency Rda 1.2-1.7mg, higher dose by .5mg by day are advised for pregnancy lactation Galactoflavin is antimetabolite of riboflavin
  • Glossitis…… swelling, smooth (loss of pappilae), colour changes, painless or painful, difficulty with chewing, swallowing &amp; speaking Cheilosis...... inflammatory lesion at the labial commissure, or corner of the mouth, and often occurs bilaterally Stomatitis…. inflammation of the mucous lining of any of the structures in the mouth sore and raw tongue, lips, throat, ulcers in mouth; vascularization of cornea. Dry scaly skin, loss of hair; anaemia and neuropathy develop later
  • active coenzyme forms of niacin are formed in the liver Nicotinic acid (niacin) - Pyridine derivative …………….. amide form - nicotinamide (niacinamide) NAD and NADP participates in &gt;200 metabolic reactions in the body little cooking loss
  • Tryptophan forms Niacin in the presence of B6 60 mg of Tryptophan forms 1mg of Niacin Thus, daily requirement of niacin is affected by the amount of tryptophan in diet
  • The large doses needed for hypolipidaemic action are poorly tolerated. Only about half of the patients are able to take the full doses. Nicotinic acid is a cutaneous vasodilator: marked flushing, heat and itching (especially in the blush area) occur after every dose. This can be minimized by starting with a low dose taken with meals and gradually increasing as tolerance develops. Aspirin taken daily largely prevents the reaction (PGs may be involved). Dyspepsia is very common; vomiting and diarrhoea occur when full doses are given. Peptic ulcer may be activated. Dryness and hyperpigmentation of skin can be troublesome. Other long-term effects are: Hyperglycaemia, precipitation of diabetes (should not be used in diabetics) . Hyperuricaemia and gout, atrial arrhythmias. It is contraindicated during pregnancy and in children. It is highly efficacious in hypertriglyceridaemia (type III, IV, V) whether associated with raised CH level or not. It is mosth· used to lower VLDL and raise HDL levels, and as an adjunctive drug to statins/ fibrates. Nicotinic acid is the most effective drug in reducing plasma TG levels and controlling pancreatitis in genetic type IV and type V disorders. Long-term use prevents further attacks of pancreatitis. Given over long-term in post-Ml patients, it has been found to reduce recurrences of MI and overall mortality. However, because of marked side effects, use of nicotinic acid is restricted to high-risk cases only.
  • This action is unrelated to its vitamin activity and not present in nicotinamide. When nicotinic acid is given, TGs and VLDL decrease rapidly, followed by a modest fall in LDL-CH and total CH. Nicotinic acid is the most effective drug to raise HDL-CH; Nicotinic acid reduces production of VLDL in liver by inhibiting TG synthesisIt inhibits intracellular lipolysis in adipose tissue and increases the activity of lipoprotein lipase that clears TGs. A cell surface G-protein coupled receptor which negatively regulates adipocyte adenylyl cyclase has been found to selectively bind nicotinic acid, and has been called &apos;niacin receptor&apos;. Nicotinic acid appears to inhibit lipolysis in adipose tissue by decreasing hormone stimulated intracellular cAMP formation through this receptor. Hepatic VLDL production is believed to be decreased due to reduced flow of fatty acids from adipose tissue to liver.
  • Deficiency leads to hemolytic anemia.
  • These pyridine nucleotides act as hydrogen acceptors In the electron transport chain in tissue respirati on, glycolysis and fat synthesis. Flavoproteins regenerate them by oxidizing N ADH and NADPH. Nicotinic acid (but not nicotinamide) in large doses is a vasodilator, particularly of cutaneous vessels. It also lowers plasma lipids
  • Oennatitis-sunburn like dermal rash on hands, legs and face which later turn black, crack and :&apos;eaL Diarrhoea-with enteritis, stomatitis, glossitis, oalivation, nausea and vomiting. Dementia-with hallucinations preceded by headache, insomnia, poor memory, motor and sensory disturbances. Anaemia and hypoproteinaemia are common in pellagra. Chronic alcoholics are particularly at risk of developing pellagra, because in addition to dietary deficiency, niacin absorption is impaired in them. Other B vitamin deficiencies are often associated.
  • Conversion of Tryptophan to Niacin is dependent on pyridoxal phosphate Anti-tubercular drug which inhibits pyridoxal phosphate formation.
  • and small quantities of pantothenic acid are found in nearly every food.
  • impaired energy production, due to low CoA levels Acetylcholine synthesis is also impaired.....Insulin receptors are acylated with palmitic acid when they do not want to bind with insulin nearly all symptoms can be reversed with the return of pantothenic acid...........
  • because raw egg white contains the protein avidin which binds biotin at an extraordinarily high affinity, thus causing deficiency. Biotin is covalently bound to lysine in the enzymes to form ” Biocytin ”…active form Biotinidase allows the body to use and to recycle biotin.........The enzyme biotinidase cleaves biocytin and makes biotin available to be reused by other enzymes
  • Widespread in foods
  • Break down of leucine
  • Dermatitis……Red, scaly rash around the eyes, nose &amp; mouth Toxicity symptoms : none reported
  • Pyridoxine---plant source………….rest-----food of animal origin
  • Non-citrus fruits Daily Value set at 2 mg……..Average intake is more than the RDA
  • Low levels of folate can also lead to homocysteine accumulation
  • A complete lack of dietary folate takes months before deficiency develops as normal individuals have about 500–20,000 µg of folate in body stores. NTD is an opening in the spinal cord or brain that occurs very early in human development……….all women… 0.4 mg/day
  • Makes it difficult to diagnose b12 deficiency
  • A  vitamer  of a particular vitamin is any of a number of chemical substances, each of which shows vitamin activity. Very commonly each &quot;vitamin&quot; is not a single chemical, but rather multiple chemical substances called  vitamers , each of which is defined by its different biological activity.
  • Average intake exceeds RDA…….stored in the liver………… Non-toxic Vegans are at risk of deficiency
  • elevated levels of MMA, a myelin destabilizer
  • Takes ~20 years on a deficient diet to see nerve destruction…………… Injection of B-12 needed Pernicious……… is one of many types of the larger family of megaloblastic anemias .
  • The name given to the vitamin that the fruit provided, ascorbic acid, literally means “no scurvy acid” Excess excreted……………Easily lost through cooking
  • Average intake ~72 mg/day…………Fairly nontoxic (at &lt;1 gm)……….Upper Level is 2 g/day Warning to people with hemochromatosis, oxalate kidney stones
  • Deficient for 20-40 days ………….. Most scurvy symptoms are due to collagen breakdown Rebound scurvy……………… immediate halt to excess vitamin C supplements Who is at risk?................ Infants, elderly men Alcoholics, smokers
  • Salts of ascorbic …….. no indigestation Larger amounts of Vitamin C lower  Manganese  levels and aid greater insulin production acid…..
  • metabolic role and therapeutic use of b complex vitamins

    1. 1. Vitamin Defined ‘An organic substance that occurs in foods in small amounts and is necessary for normal metabolic functioning of the body’ VITAMIN” means “vital for life”  May be water soluble or fat soluble  Do not contribute directly to the structure of the body, nor do they supply energy.  They regulate metabolism by releasing energy from fats and carbohydrates  They are involved in amino acid metabolism and also assist in forming blood, bones and tissues
    2. 2. Essential Vitamins For Human Being vitamins water -soluble lipid-soluble Vit C Vit B A,D,E,K B1, B2, B6, B12, PP, patothenic acid , folic acid,biotin ,lipoic acid
    3. 3. Overview of Water Soluble Vitamins Heterogeneous( differ chemically) Dissolve in water Readily excreted through urine Continuous supply needed Non-toxic Cooking losses Function as a coenzyme Generally deficiencies due to water soluble vitamins are multiple rather than individual with overlapping symptoms.
    4. 4. • The water soluble vitamins form coenzymes (active form of the vitamin). Co-enzyme
    5. 5. Co-enzyme
    6. 6. Thiamine- Vitamin B-1 • “thio”-vitamin (sulfur-containing vitamin) • Ist vitamin to be identified • Other names – Anti neuretic – Anti Beri Beri • Only synthesized by bacteria, fungi & plants • Animals must obtain it from their diet
    7. 7. • Relatively unstable -Destroyed with heat and in alkaline environment -Lost by milling flour, leaching into cooking liquids and in thawing frozen food • Co-enzyme: helps release energy from carbohydrates
    8. 8. Thiamine Sources  Pork, hot dogs & luncheon meat  Cold cereals  Sunflower seeds  Green beans  Whole/Enriched Grains
    9. 9. RDA and Toxicity • 1to 1.5 mg/day • Requirement increases in pregnancy & lactation(2mg), old age & alcoholism. • Daily intake depends on carbohydrate metabolism Toxicity • Upto 50mg/d can brought to control • anaphylaxis
    10. 10. Pyrimidine Thiazole The Active Form • Thiamine contains an aminopyrimidine ring and a thiazole ring. • Active forms - Thiamine Pyrophosphate Thiamine triphosphate • The TPP reaction is catalyzed by enzyme thiamine pyrophosphate transferase. • Activation occurs mainly in liver.
    11. 11. Biochemical Functions Needed for the metabolism of carbohydrates, proteins and fats Thiamine pyrophosphate (TPP) is involved with the energy releasing reactions of carbohydrate metabolism. Glycolysis TCA cycle 10–15 % of total energy in the form of ATP. Oxidative Phosphorylation 85–90% of total energy in the form of ATP. GLYCOLYSIS TCA Cycle
    12. 12. Oxidative Decarboxylation reactions  Pyruvate Dehydrogenase (PDH)  α Ketoglutarate Dehydrogenase. Transketolation reaction  Transketolase.in HMP shunt pentose sugar (ribose)  hexose sugar (glucose) which is then used to produce energy in the form of ATP. GLYCOLYSIS TCA Cycle Reactions requiring TPP
    13. 13. The branched chain aminoacid dehydrogenase (decarboxylase)  Leucine, isoleucine , valine to form keto acid. Pts of Maple syrup disease(defect in decarboxylation reaction) are treated with large dose of thiamine Transmission of nerve impulse  TPP is required for acetylcholine synthesis and ion translocation of neurnal tissue. Thiamine triphosphate form is also involved.
    14. 14. Absorption, Transport & Metabolism • Absorbed in the upper small intestine – Low concentration = carrier mediated – High concentration = passive diffusion • Transported by RBC in the blood(90% of total thiamine of blood ) • Excreted in the urine
    15. 15. Thiamine Deficiency Causes: • Inadequate Diet (polished rice) • Alcoholism • chronic illness(liver cirrhoses, disease affecting absorbtion in small intestine,cancer) • Pregnancy and lactation • Thiaminase ( in raw fish) inactivates thiamine by breaking the thiazole ring.
    16. 16. Deficiency Women with hyperemesis gravidarum and anorexia • Pt on parental glucose • Pt on chronic diurectic therapy • Maternal thiamine def in breast fed child, Infantile • Increased Carbohydrate intake • Increased metabolic activity due to Hyperthyroidism and fever
    17. 17. Thiamine Deficiency Biochemical Changes:  Carbohydrate metabolism is impaired.acc of pyruvate in tissues  Increased pyruvate concentration and is excreted in urine.  Increased pyruvate in plasma  Lactate  Lactic acidosis  Inc permeability of Blood Brain Barrier. Pyruvate entry & brain directed poly neuritis  The transketolase activity in erythrocytes is decreased. Who is at Risk For Deficiency?  Poor , Alcoholics, Elderly, Diet consisting of highly processed foods
    18. 18. Clinical manifestations Deficiency leads to Beri-beri which is of three types.  Wet Beri-beri: CVS manifestations are prominent  Edema of legs, face & trunk  Pleural effusion & ascites  Breathlessness and palpitation. systolic murmurs  Fast and bouncing pulse  Weak heart muscles resulting in death due cardiac failure.
    19. 19. Clinical manifestations  Dry Beri-beri: CNS manifestations prominent.  Edema not commonly seen.  Neurological manifestation resulting from accumulation of pyruvate in the nerves.  polyneuritis with numbness , loss of nerve transmission resulting in 'wrist drop', 'foot drop', irritability, poor arm/leg coordination even paralysis of whole limb.  mental changes, sluggishness, poor memory, loss of appetite and constipation  Infantile Beri-beri: Seen in infants born to mothers suffering from thiamine deficiency. Sleeplessness, restlessness, vomiting, convulsions and finally death.
    20. 20. Clinical manifestations Wernicke-Korsakoff syndrome: Seen in chronic alcoholics and is characterized by:  Loss of memory  Apathy (absence of emotions)  Nystagmus (rhythmical to-and-fro motion of the eyeballs)  Ataxia (Unstable gait)  Opthalmoplegia (paralysis of the eye muscles)  Encephalopathy: Congestion and hemorrhages in parts of the brain.
    21. 21. Lab diagnosis Lack of nerve impulse transmission RBC transketolase activity is dec, its measurement is diagnostic This is the earliest indicator and reliable diagnostic test to assess thiamine deficiency HPLC measures thiamine and its phosphorylated esters in serum or blood is measured.
    22. 22. Therapeutic Use • 1 . Prophylactically (2-10 mg daily) in infants,pregnant women, chronic diarrhoeas, patients on parenteral alimentation. Glucose infusion unmasks marginal thiamine deficiency. • 2. Beriberi-100 mg/day i.m. or i.v. till symptoms regress-then maintenance doses orally. • 3. Acute alcoholic intoxication: thiamine 100 mg is added to each vac of glucose solution infused. Most neurological symptoms in chronic alcoholics are due to thiamine deficiency-peripheral neuritis, Wernick's encephalopathy, Korsakoff'spsychosis: give 100 mg/ day parenterally.
    23. 23. 4. In neurological and cardiovascular disorders, hyperemesis gravidarum, chronic anorexia and obstinate constipation- thiamine has been used even without definite proof of its deficiency.symptoms improve dramatically if thiamine deficiency has been causative. 5. Maple syrup disorder Adverse effects Thiamine is nontoxic. Sensitivity reactions sometimes occur on parenteral injection.
    24. 24. Riboflavin (Vit. B2) • The name "riboflavin" comes from “ribose” and “flavin” • Coenzymes: – Flavin mononucleotide (FMN) – Flavin adenine dinucleotide (FAD) • Stable to heat but sensitive to light (photosensitive). When exposed to UV rays it gets destroyed • Oxidation-reduction reactions • Electron transport chain • Citric Acid Cycle • Drug and steroid metabolism, including detoxification reaction (called the drug vitamin)
    25. 25. Riboflavin Sources • Milk/products – Yogurt, Cheese • Meat & eggs • Liver • Enriched /whole grains • Oyster • Brewer’s yeast • Tryptophan rich food RDA – 1.1 mg/day for women
    26. 26. Absorption, Transport, & Metabolism • HCL in the stomach releases riboflavin from its bound form • Absorption – Active or facilitated transport during low to moderate intake – Passive absorption during high intake • Transported by a protein carrier in the blood • Excess riboflavin is excreted unchanged in the urine
    27. 27. Active Coenzymes of Riboflavin • FMN: Flavin mononucleotide: Formed in the intestine by phosphorylation of Riboflavin in the presence of enzyme ‘Flavokinase’ • FAD: Flavin adenine dinucleotide: Formed in the liver from FMN by the transfer of an AMP from ATP . FAD = FMN + AMP
    28. 28. Functions •Growth promoting factor: –Repair & development of body tissues - healthy skin •Act as “coenzymes” in many reactions including the oxidation-reduction reactions and electron transport chain. by serving as an acceptor of two hydrogen atoms (with electrons) FMN  FMNH2 FAD FADH2 Accepts electrons Electron Transport Chain FAD FADH2 Succinate Fumarate Citric Acid Cycle Assist in the metabolism carbohydrates, protein and fats
    29. 29. Who is at Risk For Deficiency?  Rare, usually with other vit b deficiency  Low milk/dairy intake Gastrointestinal disease that causes vomiting and hypermotility of the gastrointestinal tract Phototherapy (neonatal jaundice)  Pregnancy & lactation  Alcoholics Long term phenobarbital & Chlorpromazine use
    30. 30. Deficiency • Ariboflavinosis: – Glossitis, cheilosis & angular stomatitis – Sore & raw tongue – seborrheic dermatitis – Loss of appetite – Dry scaly skin, loss of hair – anaemia and neuropathy – vascularization of cornea – Occurs within 2 months – Most often seen in association with protein energy malnutrition – Also in cases of alcoholism
    31. 31. • Deficiency can be seen in anorexia , malabsorbtion. • Drugs eg. Barbiturates (microsomal oxidation of vitamin) • Symptoms of ariboflavinosis are relatively mild and not life threatening because • 1 riboflavin are associated with protein diet. • 2.recycling of riboflavin from FMN & FAD is very efficient.
    32. 32. Lab Diagnosis • Lab measurement of RBC and urinary riboflavin • Measurement of erythrocyte glutathoine reductase activity (deficiency)as an index of riboflavin status Therapeutic uses • To prevent and treat ariboflavinosis(2-20 mg/ day oral or parenteral), generally along with other B complex members.
    33. 33. Niacin (Vit. B3) • 2 Forms – Nicotinic acid (niacin) – Nicotinamide (niacinamide) • Coenzyme (liver) – Nicotinamide adenine dinucleotide (NAD) – Nicotinamide adenine dinucleotide phosphate (NADP) – oxidation-reduction & oxidative-phosphorylation reactions • Heat stable • A peculiar vitamin since it can be synthesized in body (via tryptophan) 60mg of tryptophan is equivalent to 1 mg of niacin for the synthesis of niacin coenzyme(B6)
    34. 34. Niacin Sources • All protein foods • Milk, eggs, meat, fish, poultry • Whole/Enriched grains • Nuts, Mushrooms • Can be synthesized endogenously from Tryptophan. • Tryptophan rich food RDA • 15 – 20 mg/day
    35. 35. Absorption and Metabolism • Absorbed in the upper part of the small intestine • It is stored only sparingly in the kidney, heart, brain, and liver and is exreted in the urine
    36. 36. RDA Adult 15-20mg/d children 10-15mg/d Niacin equivalent = 1mg niacin= 60mg tryptophan ma ize eaters have suffered from pellagra because corn flour is poor in tryptophan and it is believed to contain a niacin antagonist. Thus, daily requirement of niacin is affected by the amount of tryptophan in diet
    37. 37. acid. 3. Hartnup's disease: in which tryptophan transport is impaired, and in carcinoid tumours which use up tryptophan for manufacturing 5-HT, need niacin supplementation. 4. Nicotinic acid (not nicotinamide) has been used in peripheral vascular disease and as hypolipidaemic (Ch. 45). Adverse effects Nicotinic acid, in pharmacological doses, has many side effects and toxicities (p. 618). Nicotinamide is innocuous. Pyridoxi
    38. 38. • The oxidation–reduction reactions catalyzed by enzymes belonging to ‘oxido-reductases’ • α- ketoglutarate Succinyl CoA NAD+ NADH + H+ • Malate Oxaloacetate NAD+ NADH + H+ TCACycle NAD+ Functions • Forms the active portion of the coenzymes(40) that play an essential role in cells.
    39. 39. Glucose-6P 6-phospho-gluconolactone NADP+ NADPH + H+ PentosePhosphate pathway • The Oxidative-Phosphorylation: NADH that is produced in TCA cycle, will undergo oxidative phosphorylation (NADH + H+ into NAD+ ) in the Electron Transport Chain to generate ATP. • Responsible for major energy production in the form of ATP. 1 NADH = 3 ATP NADP+ Functions
    40. 40. Functions  NADPH is important in Reductive Anabolic Pathways (Reductive Biosynthesis) by donating reducing equivalents (NADPH + H+ into NADP+ ).  No energy is produced.  NADPH is also required to maintain the structure of erythrocyte membrane. (Deficiency leads to hemolytic anemia)
    41. 41. Function • . Flavoproteins regenerate them by oxidizing N ADH and NADPH. • Nicotinic acid (but not nicotinamide) in large doses is a vasodilator, particularly of cutaneous vessels. • It also lowers plasma lipids(in large doses)
    42. 42.  Pellagra [3 D’s] – Dermatitis • scaly dermatitis • sun exposed surfaces of skin • starts as red pigmentation which turn to be dark later – Dementia • Confused & disoriented – Diarrhea • irritation/inflammation of mucous membranes – Reduced appetite & weight. – Occurs in 50-60 days. – Prevented with an adequate protein diet Deficiency
    43. 43. Deficiency • Pellagra – characterized as the disease causing 4D’s – Dermatitis – Diarrhea – Depression – Death
    44. 44. Symptoms • Weakness • Persistent fatigability • Irritability • Headache • Depression • Soreness and inflammation of the tongue (glossitis) and mouth (stomatitis)
    45. 45. Laboratory assessment • Urinary excretion of niacin metabolites  N-methyl nicotinamide  2-pyridone
    46. 46. Causes of Deficiency  Vitamin B6 deficiency  Isoniazid:  Hartnup Disease: Tryptophan absorption from intestine is defective.  Pregnancy and Lactation  Corn as main staple  Poor diet & alcoholics
    47. 47. Niacin as a Medicine • Inhibits lipolysis in adipose tissues • 75-100 x RDA can lower LDL and TG and increase HDL • Slow/ reverse progression of atherosclerosis with diet and exercise • Toxicity effects – Flushing of skin – Itching – Nausea – Liver damage – Hyperuricemia (exacerbate gout)
    48. 48. Pantothenic Acid • Vitamin B-5 • Its name derives from the Greek word pantothen meaning "from everywhere“. • Easily destroyed by food processing • Part of coenzyme A, used in energy metabolism • Essential for metabolism of CHO, fat & protein
    49. 49. Pantothenic acid Sources • Widespread in foods • Meat, Liver • Milk • Mushrooms • Avacado • Peanuts • Broccoli • Whole grains RDA • 5 mgs/day
    50. 50. Structure: •Pantothenic acid contains β alanine and pantoic acid. •The active Coenzyme A (CoA) differs according to the group added in place of H in the –SH (sulphahydryl group)  Acetate is added to form acetyl CoA.  Succinate is added to form succinyl CoA.
    51. 51. Biochemical functions Acetyl CoA  TCA cycle  Acetyl choline synthesis (neurotransmitter)  Fatty acid metabolism Succinyl CoA  Heme synthesis • Toxicity symptoms: none reported
    52. 52. Deficiency • Rare • Usually in combination with other deficiencies • Signs/symptoms  Irritability, fatigue & apathy  Neurological symptoms: numbness, paresthesia & muscle cramps  Hypoglycemia d/t increased sensitivity to insulin  Restlessness, malaise, sleep disturbances, nausea, vomiting & abdominal cramps.  Burning foot syndrome: painful burning sensations of the feet • Alcoholics at risk
    53. 53. Biotin • Vitamin B-7 & Vitamin H • Anti Egg White Injury Factor: Avidin, a protein found in raw egg white, inhibits the absorption of biotin. • Free and bound form • Biocytin (protein bound form) • Biotinidase (allows the body to use and to recycle biotin)
    54. 54. Biotin Sources: • Organ meats, fish • Egg yolks • Soybeans • Whole grains • Cheese • Peanuts • Also produced by GI bacteria RDA: • 30 µg/day
    55. 55. Active form of Biotin acts as coenzyme for Carboxylation reactions (addition of carbon in the form of CO2). Examples: Carboxylation of Acetyl CoA ( Biosynthesis of FA) Acetyl CoA + CO2 Malonyl CoA Carboxylation of Pyruvate (Gluconeogenesis) Pyruvate + CO2 Oxaloacetate Metabolism of fat & amino acids (leucine) Cell growth Steady blood sugar level Biochemical Functions
    56. 56. Signs/symptoms:  Hair loss (alopecia)  Depression, lethargy, hallucinations, numbness and tingling of the extremities  Dermatitis  Conjunctivitis Causes:  Raw eggs  Biotinidase deficiency  Alcoholics  Antibiotics Deficiency
    57. 57. Vitamin B-6  Various forms: [pyridine derivatives] – Pyridoxine – Pyridoxal – Pyridoxamine  Pyridoxal phosphate [PLP] – active coenzyme form  Heat and alkaline sensitive  RDA: – 1.3 mg/day for adults – 1.7 mg/day for men over 50 – 1.5 mg/day for women over 50
    58. 58. Vitamin B6 Sources • Meat, fish, poultry, liver • Potatoes, Legumes • Banana • Spinach • Avocado • Whole grains • Soy products
    59. 59. Absorption, Transport & Metabolism • Absorbed passively • Binds to albumin for transport in the blood • B-6 is stored in the liver and muscle tissue • All three forms of B-6 are phosphorylated in the liver • Excess is excreted in urine
    60. 60. Functions • Amino acid metabolism Transamination Deamination Decarboxylation (Histamine synthesis) Condensation (Haemoglobin synthesis) Racemization (Structural rearrangement of amino acids) • Carbohydrate metabolism Gluconeogenesis • Lipid metabolism Biosynthesis of sphingolipids • Neurotransmitter Synthesis • Gene expression • Conversion of tryptophan to niacin
    61. 61. Deficiency  Microcytic hypochromic anemia  Seborrhoeic dermatitis  Atrophic glossitis with ulceration  Angular cheilitis  Conjunctivitis  Neurological symptoms – Drowsiness, depression, confusion & neuropathy Causes Isoniazid Alcoholics OCPs Elderly
    62. 62. B-6 As A Medicine • Morning sickness in early pregnancy • PMS • Mental depression • Cut the risk of parkinson’s disease by half • Carpal tunnel syndrome Toxicity potential • Can lead to irreversible nerve damage with doses > 2 g/day
    63. 63. Folic acid • From the Latin word “folium” (which means “leaf”) • Other names Folacin Vitamin B-9, Vitamin M & Vitamin Bc • Consists of Pteridine group Para-amino benzoic acid (PABA) and Glutamic acid • Coenzyme form: Tetrahydorfolic acid (THFA) Dihydrofolic acid (DHFA) • Susceptible to heat, oxidation & ultraviolet light
    64. 64. Folic acid Sources • Leafy Green Vegetables • Fortified Grains • Legumes, Seeds • Liver RDA • 400 ug/day for adults
    65. 65. Absorption, Transport & Metabolism • Absorbed in the monoglutamate form with help of folate conjugase – Active absorption = low to moderate intake – Passive absorption = high intake • Delivered to the liver where it is changed back to the polyglutamate form • Mostly stored in the liver • Excreted in urine and bile (entero-hepatic circulation)
    66. 66. Functions • Synthesis, repair & methylation of DNA – Transfer of single carbon units – Synthesis of amino acids, purines & thymidine mono-phosphate • Cell division & growth • Homocysteine metabolism • Produce healthy red blood cells & prevent anemia
    67. 67. Deficiency  Sign/symptoms – Anemia (megaloblastic) – Neural tube defects (in developing embryo) – Peripheral neuropathy – Glossitis with peptic and mouth ulcers – Mental confusion, depression, weakness, fatigue & irritability – Headache, diarrhea & palpitations – Cancer development  At risk – Pregnant women – Alcoholics
    68. 68. Megaloblastic Anemia
    69. 69. Toxicity • Risk is low • Upper limit  1 mg/day – adult men & women  0.8 mg/day – women < 18 yrs of age • Signs  Epilepsy  Skin & respiratory disorder • Excess can mask vitamin B-12 deficiency
    70. 70. Vitamin B-12 • Also known as cobalamin • contains cobalt • Consists of a class of chemically-related compounds (vitamers)  Methyl-cobalamin  Adenosyl-cobalamin  Hydroxo-cobalamin  Cyano-cobalamin (synthetic form) • Basic structure: Synthesized only by bacteria, fungi and algae • Heat stable up to 100°C • Affected by strong acids/alkalis • Affected by light
    71. 71. Vitamin B12 Sources: • Animal products – Meat, poultry, fish, shellfish – Milk, cheese – Eggs • Fortified cereals RDA: • 3-4 ug/ day
    72. 72. Absorption & Metabolism
    73. 73. Functions  Citric acid cycle  Nerve functions  Maintains myelin sheath  Folic acid metabolism  RBC formation & prevents megaloblastic anemia  t/t of pernicious anemia
    74. 74. Deficiency  Megaloblastic anemia – Delayed or failure of normal cell division due to impaired DNA synthesis Pernicious anemia – Destruction of parietal cells – Achlorhydria & atrophic gastritis Neuropathy – defective myelination – never degeneration – progressive peripheral weakening – Tingling/numbness in the extremities (parasthesia)
    75. 75. Vitamin C • Vitamers of vitamin C – Ascorbic acid (reduced form) – Salts of ascorbic acid • Vitamin C is purely the L-enantiomer of ascorbic acid • Synthesized by most animals (not by human) • The name is derived from ”a”- (meaning "no") and ”scorbutus” (scurvy) • RDA  90 mg/day for male adults  75 mg/day for female adults  +35 mg/day for smokers
    76. 76. Vitamin C Sources – Citrus fruits – Potatoes – Green peppers – Cauliflower – Broccoli – Strawberries – Lettuce & spinach
    77. 77. Functions  Reducing agent (antioxidant)  Boost Immunity  Iron absorption  Collagen synthesis  Healthy blood vessels  Promotes wound healing  Synthesis of carnitine & tyrosine  Anti-histaminic  Prevents histamine release  Increases the detoxification of histamine
    78. 78. Collagen Synthesis
    79. 79. Deficiency  Scurvy Early symptoms  Malaise & lethargy After 1-3 months  Easy bruising & petechiae  Bleeding gums & loose teeth  Swollen ankle & wrists  Poor wound healing  Shortness of breath, fatigue & weakness  Bone pain & myalgia  Anemia & cessation of growth
    80. 80. Toxicity Adverse effects (doses > 2 gms/day): • Indigestion & diarrhea • Iron poisoning (in people with iron overload disorders) • Suppresses the production of progesterone from corpus luteum • Increases insulin production • Interference with blood coagulation therapy • Kidney stones [oxalate] • Gout
    81. 81. Thank You A presentation by Akif Ahsan
    1. A particular slide catching your eye?

      Clipping is a handy way to collect important slides you want to go back to later.

    ×