Vitamin St2(1)
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Transcript of Vitamin St2(1)
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itamin
Sekelompok nutrien organik yangdibutuhkan dalam jumlah sedikit
untuk berbagai macam fungsibiokimiawi
* Biasanya tidak dapat disintesis oleh
tubuh, sehingga harus ada dalamdiet
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Vitamin yg larut dalam air
1. Vitamin B-complex
a) vitamin B untuk metabolisme energi (Co enzim)Thiamine (B1)Riboflavin (B2)Niacin (B3)Biotin
Pantothenic acid
b) vitamin B untuk metabolisme konversi gugus metilFolic acid (asam folat)Cobalamin (B12)
c) Vitamin B untuk konversi metabolikPyridoxine (B6)PyridoxalPyridoxamine
2. Vitamin C
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B Complex Digestion
Broken down from coenzyme form into freevitamins in the stomach and small intestine
Absorbed, primarily in the small intestine(50%-90%)
Once inside cells, coenzyme forms are
resynthesizedNo need to ingest coenzyme forms; we canmake them
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O-
O
O
H3C
S
O
H3CCoA CO2+
pyruvate acetyl CoA
pyruvate dehydrogenase complex
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Champe and Harvey, p. 106
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O
H3CO
O-
N
N
N+
S
H3C
NH2 H
HO
N
N
N+
S
H3C
NH2 CH
O
P OP O
-
O
-O
O
-
O
H3C OH
N
N
N+
S
H3C
NH2 H
O
P OP O
-
O
-O
O
-O
CO2
thiamine (B1)
thiamine pyrophosphate TPP
first step in pyruvate dehydrogenase complex
+
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ThiamineFood sources and distribution:
Whole grain, meats, legumes (peas, beans and lentils)
Signs and symptoms of deficiency
Beri-beri: severe deficiencyPrimarily in areas where polished rice is primary food source
Symptoms include dry skin, irritability, disorderly thinking and
progressive paralysis
Wet beriberi-cardiovascular symptoms, cardiac failure
Infants: onset can be rapid, resulting in tachycardia and death(look to nutritional status of mother)
Wernicke-Korsakoff syndrome:Primarily associated with severe alcoholism.
Symptoms include apathy, loss of memoryWandering eye movement
Toxicities, contraindications, and other notes
Only known use in treating deficiency
Commonly given to alcoholics in ER(emergency room)
Excess of any one B-vitamin can cause deficiency of others.
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Rubin and Farber,Pathology - 2ndedition, p. 329
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Wet and Dry BeriBeri
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RDA For Thiamin
1.1 mg/day for women
1.2 mg/day for men
Daily Value on food label is 1.5 mg
Most exceed RDA in diet
Low income people and older people may
barely meet needs (highly processed andunenriched foods, sugar, fat, alcohol)
Surplus is rapidly lost in urine; non toxic;
no Upper Level
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Alcohol and Thiamin
Alcoholics are at greatest risk for thiamin
deficiency because absorption and use of
thiamin are profoundly diminished andexcretion is increased by alcohol
consumption
Poor quality diet makes it worse Little stored in body, so alcoholic binge of
1-2 weeks may result in deficiency
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RiboflavinFood sources and distribution:
Milk, cheese, meat, leafy vegetables,
breads, cereals
Signs and symptoms of deficiency
Sore throat, glossitis, cheilosis (red lips)
Anemia, neuropathy
Toxicities, contraindications and other notes
Only known use in treating deficiency
Excess intake can cause yellow urine
Excess can interfere with B1 & B6
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Rubin and Farber,Pathology - 2ndedition, p. 331
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N
N
N
NH3C
H3C
O
H
O
CH2
OH
OH
OH
OH
CH2
OH
OH
OH
O P
O P
O
O N
NN
N
NH2
OHHO
O
-O
-O
N
N
N
NH3C
H3C
O
H
O
O
N
N
N
NH3C
H3C
O
H
O
H
H
FADH2
riboflavin (B2)
Flavin adenine dinucleotide FAD
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N+
O
NH2
H
N+
O
O-
H
N+
O
NH2
N
NN
N
O
O
NH2
OHHO
OH
OH
O
O
P
P
O
OO
-
O
-O
H NADH
N
O
NH2
H H
niacin (B3)
nicotinamide
nicotinamide adenine dinucleotide NAD+
H-
= H+
+ 2e-
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Food Sources of Riboflavin Milk/products
Enriched grains
Ready to eat cereals
Liver
Oyster
Brewers yeast
Vegetables (asparagus, broccoli, greens)
Sensitive to uv radiation (sunlight)
Stored in paper, opaque plastic containers
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RDA for Riboflavin
1.1 mg/day for women
1.3 mg/day for men
Average intake is above RDA
Toxicity not documented
No upper level
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niacin
Nicotinic acid and nicotinamide
Food sources and distribution:
Fish, meat, poultry, cereal, nuts
Tryptophan in diet can serve as alternative source
Signs and symptoms of deficiency
Pellagra (pella agra: rough skin)3Ds: dermatitis, diarrhea, dementia
red, swollen tongue
observed in chronic alcoholics
symptoms reverse within 24H of administration
Toxicities, contraindications and other notes
Harnups disease: defective renal and intestinal transport of tryptophan
Fast growing tumors can exhaust tryptophan supply
Excess can cause high BP and uric acid, cardiac arrhythmias
Can lower cholesterol
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Rubin and Farber,Pathology - 2ndedition, p. 330
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Pellagra
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RDA for Niacin
14 (mg) NE/day for women
16 (mg) NE/day for men
Daily Value on labels is 20 mg
Upper Level is 35 mg
Toxicity S/S: headache, itching, flushing,
liver and GI damage
Megadose can lower LDL and TG and
increase HDL
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Biotin
Food sources and distribution:
Can be synthesized by intestinal bacteria
Found in most foods
Signs and symptoms of deficiency
Very rare, include dermatitis, muscle pain
Toxicities, contraindications, and notes
Chronic consumption of raw eggs can induce
deficiency.
Chronic inflammatory bowel disease can cause
deficiency.
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Biotin
Free and bound form
Metabolism of CHO and fat
Assists the addition of CO2 to other
compounds
Synthesis of glucose, fatty acids, DNA
Help break down certain amino acids
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N N
S
O
Enzyme
HHCO2
N N
S
O
Enzyme
HC
O
-O
biotin
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N
NN
N
O
NH2
OH
OH
O
P
O
P
O
O-
O
O O-
N CH3
CH3
OH
O
H
O
N
SH
H
OHN CH3
CH3
OH
O
HO
O-
pantothenic acid
coenzyme A: CoA
acceptor site for acetyl group
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Biotin Needs
Adequate Intake is 30 ug/day for adults
This may overestimate the amount needed
for adults
Deficiency rare
No Upper Level for biotin
Relatively nontoxic
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Pantothenic (B5)
Food sources and distribution:
Ubiquitous
Easily destroyed by heating
Signs and symptoms of deficiency
Very rare
Neuromuscular degeneration
Toxicities, contraindications and other notes
Megadose can cause diarrhea and water
retention
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Review
B-complex vitamins and energy metabolism:
Thiamine B1 TPP, pyruvate dehydrogenase
Riboflavin B2 FAD, FADH2
Niacin B3 NAD+, NADH
Pantothenic acid coenzyme A
Biotin decarboxylation reactions
(decarboxylase)
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Pyridoxine (B6)
Food sources and distribution:
Meat, whole-grain breads and cereals, vegetables
Signs and symptoms of deficiency
Skin lesions
Convulsive disorders resulting from low levels of GABANeeded for NAD+ synthesis
Toxicities, contraindications and other notes
Excess can lead to sensory nerve destruction, loss of
feeling in fingers, legsExtra pyridoxine needed when using ISONAZIDE for
treatment of TB
ISONAZIDE binds covalently to pyridoxal phosphate
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N
vitamin B6
OHNH2
OH
CH3
H
+
N
OH OH
OH
CH3
H
+
N
OH O
OH
CH3
H
+
N
OO
OH
CH3
H
+
O-O
-O
pyridoxine
pyridoxamine
pyridoxal
pyridoxal phosphate
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vitamin B6 - catalyzed reactions
N
OO
OH
CH3
H
+
O-O
-O
pyridoxal phosphate
R
N
O
O-
HH
N
O
O
CH3
H
+
O-O
-O
Schiff base
R
N
O
O-
H
Transamination:
Deamination:
Decarboxylation:
Condensation:
oxaloacetate + glutamate --> aspartate + alpha ketoglutarate
serine --> pyruvate
histidine --> histamine
glycine + succinyl CoA --> gamma-aminolevulinic acid
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Folic acid
Food sources and distribution:
Fresh green vegetables
Cooking can destroy folic acid
Signs and symptoms of deficiency
Hemolytic anemias
Toxicities, contraindications and other notes.
Critical for pregnant womenMegadose can interfere with Zinc absorption.
May interfere with antiepileptic meds
(phenobarbitol)
O
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N
N N
NO
H2N
H CH3
H2N
O
O-
O
O-
O
O-
NH2
6-methylpteridine
para-aminobenzoic acid, PABA
glutamate
N
N N
N
O
H2N
H CH2
HN
O
O
O-
O
O-
NH
+
+
folate, folic acid
5
10
S
H2N
ONH2
sulfanilamide
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ONH2
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N
N NH
HN
O
H2N
H CH2
HN
O
O
O-
O
O-
NH
tetrahydrofolate, THF
5
10
OHO
O-
serine
N
N NH
HN
O
H2N
H CH2
N
O
O
O-
O
O-
NH
10-hydroxymethyl-THF
5
10
H
NH2
O
O-
glycine
H2C
OH
H
H
N
N NH
N
O
H2N
H CH2
N
O
O
O-
O
O-
NH
5,10 methylene-THF
5
10H2C
- H2O
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Stryer, Fig 29-16
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Rubin E,Pathology, p1379
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Goodman Gilman, A. The Pharmacological Basis of Therapeutics, p.1245
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Folate and Homocysteine
High homocysteine levels in blood
associated with increased risk of CVD
Folate deficiency homocysteinemia
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RDA for Folate
400 ug/day for adults
(600 ug/day for pregnant women)
Average intake below RDA
FDA limits nonprescription supplements to
400 ug per tablet for non-pregnant adults
OTC Prenatal supplement contains 800 ug
Excess can mask vitamin B-12 deficiency
Upper Level set at 1 mg
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Cobalamin (B12)
Food sources and distribution:Synthesized only by microorganisms
Deficiency usually results from absorption problem, not
availability
Signs and symptoms of deficiency:
Pernicious anemia
Megaloblastic anemia
Neurologic dysfunction
Can result in abnormal fatty acid accumulation in membranes
Toxicities, contraindications and other notesSubstantial stores of B12 are found in the body.
Could take years to develop deficiency.
Caution with patients who have had GI(gastro-intestinal)
surgery.
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Champe and Harvey, p. 327
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N
N NH
N
O
H2N
H CH2
N
O
O
O-
O
O-
NH
5,10 methylene-THF
5
10H2C
N
N NH
N
O
H2N
H CH2
HN
O
O
O-
O
O-
NH
5
10H3C
Methyl loading of methionine
5-methyl-THF
NH2
O
O-
SCH3
NH2
O
O-
SH
homocysteine methionine
methylcobalamin fromvitamin B12
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Rubin and Farber, p. 1020
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Vitamin C
Food sources and distribution:Citrus fruits, potatoes
Signs and symptoms of deficiency:
Scurvy results from deficiency in collagen hydroxylation
Results in spongy gums, loose teeth and bleeding under the skin
Toxicities and contraindications:
Can cause oxidation, particularly in presence of free metals
Can be toxic with hemodialysis patients, iron storage diseases
Ascorbate is metabolized to oxalate which can form insolubleprecipitates with Ca++
Result in low Ca++, kidney stones, heart deposits.
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Rubin and Farber,Pathology - 2nd
edition, p. 333
Vit i C d h d l di l f ti
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2 H2O2
HO
Vitamin C and hydroxyl radical formation
H2O2 + Fe2+
Fe3+
+ HO + HO-
2 O2-
+ 2 H+ H2O2 + O2
superoxide hydrogen peroxide
superoxide dismutase
2 H2O + O2catalase
Fenton reaction
ascorbic acid
DNA damage
lipid peroxidation
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Review:
Diseases associated/resulting from deficiencies in water
soluble vitamins:
BeriBeri: Vit B1
Wernicke-Korsakoff syndrome: Vit B1
Pellagra: Vit B3
Pernicious anemia: B12
Megaloblastic anemia: B12
Scurvy: Vit C
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Fat-soluble vitamins
Vitamin A
Vitamin D
Vitamin E
Vitamin K
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Rubin and Farber,Pathology - 2nd
edition, p. 328
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Goodman and Gilman, The Pharmacological Basis of Therapeutics, p. 1599
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Vitamin DFood sources and distribution:
Egg yolks, fortified milk, fish oil, sun exposure
Function: A metabolite of vitamin D is a hormone that
regulates the metabolism of calcium and phosphorus.
Signs and symptoms of deficiency:
Rickets in children
Osteomalacia (osteoporosis) in adults
Toxicities and contraindications:
The most toxic of vitamins in excess
Calcium deposits in heart, hypertension, high cholesterol
Fragile bones
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HO
HO
UV light
7-dehydrocholesterol
cholecalciferol (vitamin D3)
OHHO
(acts as a hormone-transcription factor activating expressionof Ca++-binding proteins in intestine and bone)
liver hydroxylation
kidney hydroxylationactivated by parathyroidhormone when Ca++ is low
Vitamin D
1,25 dihydroxy
1
25
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Robbins,Pathologic Basis of Disease
5thEdition, p. 1221
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Vitamin E
Food sources and distribution:
Poultry, seafood, seeds, nuts, whole wheatFunction: Reacts with and neutralizes reactive oxygen species
such as hydroxyl , radicals before they can oxidize
unsaturated membrane lipids, damaging cell
structure(antioxidant)
Signs and symptoms of deficiency:
very rare , Unknown in humans, in animal may cause
infertility
Toxicities and contraindications:
Excessive bleeding, reduced sexual function
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vitamin E
O
CH3
CH3
HO
H3CCH3
H3C
-tocopherol
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Vitamin K
Food sources and distribution:
Made by intestinal bacteria
Spinach, leafy vegetables, oats, bran, potatoes
Function:requiredfor normal blood clotting(blood
coagulation)
Signs and symptoms of deficiency:
Excess bleeding, bleeding gums
Toxicities and contraindications:Jaundice in infants
vitamin K
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O
O
vitamin K
menaquinone (vitamin K2)
required for the carboxylation of glutamate to -carboxyglutamate
allows proteins to bind calcium
N
OH
O-
O-
O
O
Ca++
important in blood clottingnewborn infants usually get a vitamin K shot
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