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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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