Vitamin

Sekelompok nutrien organik yang

dibutuhkan dalam jumlah sedikit
untuk
berbagai
macam
fungsi
biokimiawi
* Biasanya tidak dapat disintesis oleh
tubuh, sehingga harus ada dalam
diet

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 metil

Folic acid (asam folat)
Cobalamin (B12)
c) Vitamin B untuk konversi metabolik
Pyridoxine (B6)
Pyridoxal
Pyridoxamine
2. Vitamin C

Overview of Water-Soluble
Vitamins

Dissolve in water
Generally readily excreted
Subject to cooking losses
50-90% of B vitamins are absorbed
Marginal deficiency more common

B Complex Digestion
Broken down from coenzyme form into free
vitamins in the stomach and small intestine
Absorbed, primarily in the small intestine
(50%-90%)
Once inside cells, coenzyme forms are
resynthesized
No need to ingest coenzyme forms; we can
make them

pyruvate dehydrogenase complex

O
O
OCoA

H3 C

H3C

pyruvate

acetyl CoA

CO2

Champe and Harvey, p. 106

NH2

NH2
N

H3C

H
+

N+

S
H3 C

N
HO

thiamine pyrophosphate TPP O

-

NH2
O

H3C

O
P OO

OH
CH

N+

O
O

O
P O

thiamine (B1)

H3C

H3C

first step in pyruvate dehydrogenase complex

O
-

O
P O
O

O
P OO

CO2

Thiamine
Food sources and distribution:
Whole grain, meats, legumes (peas, beans and lentils)
Signs and symptoms of deficiency

Beri-beri:

severe deficiency
Primarily 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 memory
Wandering 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.

Rubin and Farber, Pathology - 2nd edition, p. 329

Wet and Dry BeriBeri

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 and
unenriched foods, sugar, fat, alcohol)
Surplus is rapidly lost in urine; non toxic;
no Upper Level

Alcohol and Thiamin

Alcoholics are at greatest risk for thiamin
deficiency because absorption and use of
thiamin are profoundly diminished and
excretion 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

Riboflavin
Food 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

Rubin and Farber, Pathology - 2nd edition, p. 331

O
H3C
H3C

N
N
N

H
O

CH2

H3C

H3C

O
N

O
H3C

N
N

N
H

OH
OH
OH
OH

riboflavin (B2)

H3C

FADH2

CH2
OH
OH
OH

NH2

P
-

N
O

P
-

HO

OH

Flavin adenine dinucleotide FAD

NH2

ON

H
H

niacin (B3)

NADH

O
NH2

H- = H+ + 2e-

N+
O

O
O

P O-

OH

O
N+

O
P

NH2

OH

NH2

N
N

nicotinamide
HO

OH

nicotinamide adenine dinucleotide NAD+

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

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

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

Rubin and Farber, Pathology - 2nd edition, p. 330

Pellagra

Pellagra
Prevented with an adequate protein diet
Enrichment Act of 1941
Became epidemic in southern Europe in early
1700s when corn became a staple food (poor
source)
Reached epidemic proportions in the
southeastern U.S from late 1800s to 1930s
Only dietary deficiency disease to reach epidemic
proportions in the US

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

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.

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

O
H N

O
N H

CO2

O
C N

N H

Enzyme
S

biotin

Enzyme
S

H
O

OH
CH3

OH

CH3

pantothenic acid

H
O

OH
CH3

N
N

SH

NH2

O
O P OO

O P O-

CH3

acceptor site for acetyl group

coenzyme A: CoA

OH
OH

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

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

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)

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 GABA
Needed for NAD+ synthesis
Toxicities, contraindications and other notes
Excess can lead to sensory nerve destruction, loss of
feeling in fingers, legs
Extra pyridoxine needed when using ISONAZIDE for
treatment of TB
ISONAZIDE binds covalently to pyridoxal phosphate

vitamin B6
OH

O
OH

OH

OH

OH
+

+
CH3

CH3

pyridoxine

pyridoxal
O
-

OH
OH
+
N

NH2

CH3

H
pyridoxamine

O
OH
+
N

CH3

H
pyridoxal phosphate

vitamin B6 - catalyzed reactions

R
O
-

O
-

H N
H

O
O-

O
-

OH
+
N

O-

O
+

CH3

H
pyridoxal phosphate

CH3

H
Schiff base

Transamination: oxaloacetate + glutamate --> aspartate + alpha ketoglutarate

Deamination: serine --> pyruvate
Decarboxylation: histidine --> histamine
Condensation: glycine + succinyl CoA --> gamma-aminolevulinic acid

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 women
Megadose can interfere with Zinc absorption.
May interfere with antiepileptic meds
(phenobarbitol)

O
S

NH2

O
H2N

sulfanilamide

6-methylpteridine
O
H

N
N

H2N

CH3
para-aminobenzoic acid, PABA

O
-

O
H2N

glutamate

NH2
O

O
O-

NH
HN 10

O
H

N
N

H 2N

CH2

O-

O
O-

folate, folic acid

O
NH
HN 10

O
H
H2N

O-

CH2

N
5

Ofolate, folic acid

O
NH
HN 10

O
H

N
5

H2N

O-

CH2

Odihydrofolate, DHF

H
O
NH
O
H
H2 N

H
N
5

N
N

N
H

HN 10
H CH
2

O
O-

O
Otetrahydrofolate, THF

NH2
H

O
OH

O
-

serine

NH

HN 10

H
N
5

H
N

O-

CH2

tetrahydrofolate, THF
H2N

N
H

NH2
O

O
OH

H2C

glycine

N 10

H
N
5

H
N
H2N

N
H

NH

O-

CH2

O-

10-hydroxymethyl-THF

O
- H2O
NH
H2C
O
H

N
5

N
H2N

N
H

N 10
CH2

O-

O
O5,10 methylene-THF

Stryer, Fig 29-16

Rubin E, Pathology, p1379

Goodman Gilman, A. The Pharmacological Basis of Therapeutics, p.1245

Folate and Homocysteine

High homocysteine levels in blood
associated with increased risk of CVD
Folate deficiency homocysteinemia

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

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 notes
Substantial stores of B12 are found in the body.
Could take years to develop deficiency.
Caution with patients who have had GI(gastro-intestinal)
surgery.

Champe and Harvey, p. 327

Methyl loading of methionine

O
O

NH
O
H

H2C

N10

N
5

CH2

H2N

N
H

O
O-

5,10 methylene-THF
O
NH

H 3C
O
H
N
5
N
H 2N

N
H

HN10
CH2

O
O

methylcobalamin from
vitamin B12

O-

5-methyl-THF
NH2
O

S
Ohomocysteine

NH2
O

S
Omethionine

CH3

RDA for Vitamin B-12

2.4 ug/ day for adults and elderly
adults
Average intake exceeds RDA
B-12 stored in the liver
Non-toxic (no Upper Level)

Rubin and Farber, p. 1020

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 insoluble
precipitates with Ca++
Result in low Ca++, kidney stones, heart deposits.

Vitamin C and collagen synthesis

OH

O
O

OH
HO

OH

vitamin C: ascorbic acid

sugar attachment site
OH

H
N

H
N

N
O

O
proline

H
N

H
N

N
O

hydroxyproline

Rubin and Farber, Pathology - 2nd edition, p. 333

Vitamin C and hydroxyl radical formation

-

2 O2 + 2 H

superoxide dismutase

H2O2 + O2
hydrogen peroxide

superoxide

catalase

2 H2O2

2 H2O + O2

Fenton reaction

H2O2 + Fe2+

HO

Fe3+ + HO

ascorbic acid

DNA damage
lipid peroxidation

+ HO

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

Fat-soluble vitamins
Vitamin A

Vitamin D
Vitamin E
Vitamin K

Vitamin A
Food sources and distribution:
Low fat dairy products, deep yellow, orange vegetables

Function: Vitamin A(retinol) is the precursor of retinel, the lightsensitive group in rhodopsin and other visual pigments.
Signs and symptoms of deficiency:
Night blindness, dry eyes and skin
Slow growth in children
Lowered resistance to infection
Toxicities and contraindications:
Overdose can result in dry skin, headache
Can result in birth defects in pregnant women
Can cause liver damage
Vitamin A derivatives (isotretinoin, accutane) can cause
birth defects and has been associated with suicide.

H3C
CH3

CH3

CH3

H3C

CH3

CH3
CH3

CH3

-carotene

CH3

CH3

CH3
CH2OH

CH3
CH3

all-trans-retinol

CH3

Rubin and Farber, Pathology - 2nd edition, p. 328

Goodman and Gilman, The Pharmacological Basis of Therapeutics, p. 1599

Vitamin D
Food 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

Vitamin D

7-dehydrocholesterol

HO

UV light

kidney hydroxylation
activated by parathyroid
hormone when Ca++ is low

25

OH
HO
1
liver hydroxylation

HO
1,25 dihydroxy cholecalciferol (vitamin D3)
(acts as a hormone-transcription factor activating expression
of Ca++-binding proteins in intestine and bone)

Robbins, Pathologic Basis of Disease 5th Edition, p. 1221

Vitamin E
Food sources and distribution:
Poultry, seafood, seeds, nuts, whole wheat
Function: 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

vitamin E

CH3
H3C

CH3

H3C

HO
CH3

-tocopherol

Vitamin K
Food sources and distribution:
Made by intestinal bacteria
Spinach, leafy vegetables, oats, bran, potatoes
Function: required for normal blood clotting(blood
coagulation)
Signs and symptoms of deficiency:
Excess bleeding, bleeding gums

Toxicities and contraindications:

Jaundice in infants

vitamin K
O

O
-

menaquinone (vitamin K2)

Ca++
O-

O
N
H
required for the carboxylation of glutamate to -carboxyglutamate
allows proteins to bind calcium
important in blood clotting
newborn infants usually get a vitamin K shot