* vitamin/ mineralaging.pharm.pusan.ac.kr/lab/lecture/2011_2/l1 수정 2011... · 2011-10-25 · 1)...

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* Vitamin/ Mineral I. Vitamin 정의 : 미량으로 생리기능의 발현에 관여하는 유기화합물 (vital amine) 대사보조를 통해 ATP 생성 종류 : 지용성 vitamin : vitamin A/D/E/K/(F) 수용성 vitamin : vitamin B group→ coenzyme vitamin C * Provitamin : 자체로는 작용 없지만 생체 내에 uptakevitamin으로 변해서 vitamin으로 작용하는 물질 Provitamin A = α-carotene β-carotene retinal retinol Provitamin D = 7-dehydrocholesterol VitaminD O 2 /bile acid retinal reductase β-carotene dioxygenase

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Page 1: * Vitamin/ Mineralaging.pharm.pusan.ac.kr/lab/lecture/2011_2/L1 수정 2011... · 2011-10-25 · 1) Vitamin C (L-Ascorbic acid) ① tyrosine의 대사에 관여 ② collagen 생성에

* Vitamin/ Mineral I. Vitamin

정의 : 미량으로 생리기능의 발현에 관여하는 유기화합물 (vital amine)

대사보조를 통해 ATP 생성

종류 : 지용성 vitamin : vitamin A/D/E/K/(F)

수용성 vitamin : vitamin B group→ coenzyme

vitamin C

* Provitamin : 자체로는 작용 없지만 생체 내에 uptake된 후 vitamin으로 변해서

vitamin으로 작용하는 물질

Provitamin A = α-carotene

β-carotene retinal retinol

Provitamin D = 7-dehydrocholesterol VitaminD

O2 /bile acid retinal reductase

β-carotene dioxygenase

Page 2: * Vitamin/ Mineralaging.pharm.pusan.ac.kr/lab/lecture/2011_2/L1 수정 2011... · 2011-10-25 · 1) Vitamin C (L-Ascorbic acid) ① tyrosine의 대사에 관여 ② collagen 생성에

1) Vitamin C (L-Ascorbic acid)

① tyrosine의 대사에 관여

② collagen 생성에 관여

③ L-ascorbic acid 2-sulfate로 되어 다당류 등의 sulfation에 관여

④ 생체이물(약물) 대사활성 유도 (특히 P-450의 증가)에 관여

⑤ 면역기능의 증강 (백혈구작용의 증가)

⑥ bile acid formation

⑦ Fe2+ 흡수증대

⑧ antioxidant

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2) Vitamin B group

Vitamin B group

함유 보효소명 주된 생리작용 결핍증

Vitamin B1

(Thiamine) TDP(Thiamine diphosphate) TPP(Thiamine pyrophosphate)

*oxidative decarboxylation

각기(beriberi)-백미섭취

Vitamin B2

(Riboflavin)

FAD (Flavin adenine dinucleotide) FMN (Flavin mononucleotide)

*redox 반응

결막염, 구순염, 설염

Vitamin B6

(Pyridoxine)

PLP (Pyridoxal phosphate) PMP (Pyridoxamine phosphate)

*amino gr transfer *amino acid decarboxylation *racem화 반응 *dehydration *heme 합성

피부염, 신경염, 구진염, Sideroblastic anemia(철아구성 빈혈)

Nicotinic acid (Niacin)

Niacinamide (Vitamin B3)

NAD (Nicotinamide adenine dinucleotide) NADP (Nicotinamide adenine dinucleotide)

*redox 반응 *VLDL저하

pellagra(거친 피부) (3D) =피부염(dermatitis) 설사 (diarrhea) 치매(dementia)

Page 4: * Vitamin/ Mineralaging.pharm.pusan.ac.kr/lab/lecture/2011_2/L1 수정 2011... · 2011-10-25 · 1) Vitamin C (L-Ascorbic acid) ① tyrosine의 대사에 관여 ② collagen 생성에

Vitamin B group 함유 보효소명 주된 생리작용 결핍증

Pantothenic Acid( Vt B5)

CoA (CoASH) (coenzyme A)

*acyl gr tranfer

피부염, 성장정지

Biotin(Vt H)

Biotin (계란의 Avidin과 결합)

*carboxylation 반응

피부염

Lipoic acid

Lipoic acid

*α-keto acid의 oxidative decarboxylation *antioxidant

Folic acid(Vt B9)

THF (Tetrahydrofolic acid)

*methyl gr tranfer 빈혈 (megaloblastic anemia)

Vitamin B12

(cobalamin)

Adenosyl cobalamin Methyl cobalamin (육류에만 존재)

*이성화반응 *methyl gr transfer *수소전이

악성빈혈 (pernicious anemia) :intrinsic factor 부족

Page 5: * Vitamin/ Mineralaging.pharm.pusan.ac.kr/lab/lecture/2011_2/L1 수정 2011... · 2011-10-25 · 1) Vitamin C (L-Ascorbic acid) ① tyrosine의 대사에 관여 ② collagen 생성에

Accept one-carbon units from donor molecules and passes them on via various

biosynthetic reactions

Factor that converts megakaryocytes to erythrocytes and platelets

Anemia and reduction of platelets

Dihydrofolate reductase (Folate reductase) inhibitor: 항암제(methotrexate), 항생제

(trimethoprim), 항말라리아약제(pyrimethamine)

Folate (folic acid) is necessary for the production of red blood cells and for the synthesis of DNA (which controls heredity and is used to guide the cell in its daily

activities). Folic acid also helps with tissue growth and cell function. In addition, it helps to increase appetite when needed and stimulates the formation of digestive acids

(Active form) (-CH2OH)

(-CH3)

(-CHO)

Atherosclerosis

Folic acid (vitamin B9)

Page 6: * Vitamin/ Mineralaging.pharm.pusan.ac.kr/lab/lecture/2011_2/L1 수정 2011... · 2011-10-25 · 1) Vitamin C (L-Ascorbic acid) ① tyrosine의 대사에 관여 ② collagen 생성에

A source of adenosylcobalamine, which is a cofactor of methylmalonyl-CoA

mutase.

This enzyme is involved in the exchange of the group –Co-S-CoA at C-2

of propionate with hydrogen atom at C-3, producing succinyl-CoA from

L-methylmalonyl-CoA.

Regulation of odd-number fatty acid and maturation factor of erythrocytes

Pernicious anemia (악성빈혈) and secretion of methylmalonic acid in urea

Metabolism of odd-chain fatty acid

Methionine synthesis

Cobalamin (Vitamin B12)

Page 7: * Vitamin/ Mineralaging.pharm.pusan.ac.kr/lab/lecture/2011_2/L1 수정 2011... · 2011-10-25 · 1) Vitamin C (L-Ascorbic acid) ① tyrosine의 대사에 관여 ② collagen 생성에

Antioxidant

Indirect involvement of a few hydroxylation reaction only.

Synthesis from gulonolactone by gulonolactone oxidase in plants and

microorganism, but not in animals including human

Prevention of transition metal oxidation

Iron adsorption (ferric→ ferrous) and development of RBC→ anemia

Dopamine β-hydroxylase (AA metabolism and steroid hormone biosynthesis)

Formation of collagen triple helix by regulating prolyl hydroxylase and lysyl hydroxylase

Scurvy (괴혈병)

O O

OH HO

HO

HO O O

OH .O

HO

HO O O

O O

HO

HO

Semidehydroscorbate

(산화형)

Dehydroscorbate

(비활성형)

Ascorbate

(환원형)

Ascorbic acid (Vitamin C)

Page 8: * Vitamin/ Mineralaging.pharm.pusan.ac.kr/lab/lecture/2011_2/L1 수정 2011... · 2011-10-25 · 1) Vitamin C (L-Ascorbic acid) ① tyrosine의 대사에 관여 ② collagen 생성에

3) Vitamin A ① 시각작용

<망막 간세포 rod에서의 vitamin A1 (Retinol)의 기능>

opsin + all-cis-retinal → rhodopsin (rod cell의 주된 light receptor)

* 이상이 있을 경우 : 암적응 비정상, 어두운 곳에서 시력↓ (야맹증)

rhodopsin (빛 흡수)

opsin 빛

all-cis-retinal all-trans-retinal의 생성 &

opsin의 conformation 변화

all-trans-retinal

all-trans-retinol (Vt A1)

blood (유리 Vt A1)

liver (Vt A1의 지방산 ester)

NADH

NAD+ + H+

opsin

transduction (G protein)

rod cell 탈분극

impulse 발생

Na channel폐쇄에 의한 Na+ 유입× Ca2+ channel open

cGMP가수분해효소 활성화 (phosphodiesterase)

Retinal isomerase

Retinol dehydrogenase

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② 골점막의 정상유지

③ 정상적인 성장

④ 생식기능 유지

⑤ 점액분비촉진

* 결핍증 ⋅ 야맹증, 결막염, 안구건조증

⋅ 뼈, 점막, 피부의 이상(피부점막의 각화, Osteopenia)

⋅ 성장지체

⋅ 생식기능 장애

* 과잉증 ⋅ 뇌압항진증상

⋅ 사지통

⋅ 간장애

Page 10: * Vitamin/ Mineralaging.pharm.pusan.ac.kr/lab/lecture/2011_2/L1 수정 2011... · 2011-10-25 · 1) Vitamin C (L-Ascorbic acid) ① tyrosine의 대사에 관여 ② collagen 생성에

4) Vitamin D(VD)

Vitamin D2 (Ergocalciferol)

Vitamin D3 (Cholecalciferol)

Vitamin D 25-OH-VD 24,25-(OH)2-VD 1,24,25-(OH)3-VD

① 혈중 Ca2+ 농도 상승

소장에서의 Ca인산 흡수촉진

VD → 25-OH-VD → 1,25-(OH)2VD 신세뇨관에서의 Ca인산의 재흡수촉진

뼈에서 Ca의 동원

간 microsome 25,26-(OH)2-VD

25-hydroxylase 1, 25-(OH)2-VD 간, 소장

담즙, 변

혈중 Ca

농도 상승

PTH (Parathyroid hormone)

신장

신장

*결핍증: 구루병, 골연화증

*과잉증: 석회화

② 유골조직(골염의 미침착의 골기질)의 석회화

③ 세포의 성장, 분화의 조절

④ 발암의 promotion과정의 억제

⑤ 면역반응(lymph구의 분화 등)에 관여

⑥ 건선병변부, 섬유아세포 증식 억제

⑦ 백혈병 치료약

⑧ 항종양작용

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5) Vitamin E

① 항산화 작용 ② 생체막 안정화 작용 ③ 면역활성화

④ 허혈성질환 방어효과 ⑤ 치매 예방

* VtE와 selenium은 상승작용을 일으킨다.

⋅ 췌장기능 활성화

⋅ GSH-Peroxidase 구성성분

⋅ lipoprotein의 vitamin E 보유에 도움

6) Vitamin K

* 장내세균에 의해 합성되고 신생아 ⋅ 유아에게 가끔 결핍

① Ca2+ 결합성 빈혈응고인자(Prothrombin 등)의 생성에 필요

② 다른 Ca2+ 결합성 단백질(Osteocalcin 등)의 생성에 필요

* dicoumarol과 wafarin(항응혈제)는 혈액응고인자 생성시에 vitamin K의 작용을 저해

Page 12: * Vitamin/ Mineralaging.pharm.pusan.ac.kr/lab/lecture/2011_2/L1 수정 2011... · 2011-10-25 · 1) Vitamin C (L-Ascorbic acid) ① tyrosine의 대사에 관여 ② collagen 생성에

1.Vitamin A (retinol)

Retinol as a hormone and as the visual pigment of the vertebrate eyes

Nuclear receptor-mediated signaling system for regulating gene expression

in the development of epithelial tissue including skin

Action mechanism

β-carotene vitamin A (retinol)

11-cis-retinal (visual pigment) all-trans-retinal neuronal signal to brain

retinoic acid Hormonal signal to epithelial cells

Dry skin, retarded development, and night blindness

Lipid-soluble vitamins

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2. Vitamin D (Calciferol)

Similar bioactivity to steroid hormone -- a kind of hormone

Synthesis from 7-hydrochoresterol by UV light in skin

Regulation of calcium uptake

Defective bone formation and the disease rickets (구루병, 어린이),

osteomalacia (골다공증, 성인)

Ergosterol으로부터 합성됨 (ergocalciferol)

7-Dehydroxycholesterol로부터 합성됨

(cholecalciferol) → hydroxylation ; 1,25

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3. Vitamin E (Tocopherol)

Biological antioxidant for protecting membrane lipids, which can cause

cell fragility

It associated with cell membrane, lipid deposits, and lipoproteins in the blood

because of its hydrophobicity.

Fragile erythrocytes

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12. Vitamin K (Phylloquinone)

Synthetic activity of blood clotting factor (Ⅱ(prothrombin ), Ⅶ, Ⅳ, Ⅹ etc) and prothrombin

in liver

Inhibition of blood clotting and hemorrhagic disease

Glu γ-carboxyGlu Factors II, VII, IX, and X

Active

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1. Calcium

Bone formation

Intracellular signaling messenger by activating kinases including PKC

Muscle contraction

Blood clotting

Synaptic signal molecule

2. Phosphorus

ATP and metabolic regulation

Biological buffering activity

Enzyme activation

A component of nucleic acids

Intracellular signaling

II. Minerals

Page 17: * Vitamin/ Mineralaging.pharm.pusan.ac.kr/lab/lecture/2011_2/L1 수정 2011... · 2011-10-25 · 1) Vitamin C (L-Ascorbic acid) ① tyrosine의 대사에 관여 ② collagen 생성에

3. Sodium and potassium

Sodium: extracellular space > intracellular space

Potassium: extracellular space < intracellular space

[K+]i < [Na+]e

Both regulates osmotic pressure of the cell

Aldosterone: readsorption of Na+ and secretion of K+ in kidney

4. Iron

Hemoglobin

Heme protein and non-heme iron protein—oxidation and reduction as well as

electron transfer

Ferritin-iron storage protein

Page 18: * Vitamin/ Mineralaging.pharm.pusan.ac.kr/lab/lecture/2011_2/L1 수정 2011... · 2011-10-25 · 1) Vitamin C (L-Ascorbic acid) ① tyrosine의 대사에 관여 ② collagen 생성에

6. Zinc

Some proteases and insulin

Transcription factors -- zinc-finger proteins

5. Cupper

Ceruloplasmin--cupper transferring glycoprotein in plasma

Superoxide dismutase

Cytochrome oxidase in mitochondrial electron transport proteins

His

Zn Zn-finger protein

Insulin hexamer

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7. Others

Magnesium: ATP stabilization

Cobalt: Vitamin B12

Selenium: glutathione peroxidase

GSH peroxidase ATP/Mg

iodoperoxidase

proteolysis T3 + T4

Tyr

HN CH CH2

C

OH

O

CH2 HO Tyr

Thyroglobin

HN CH CH2

C

OH

O

CH2 HO

I I

I

I

HN CH CH2

C

OI

O

CH2 HO

I I

I

I

HN CH CH2

C

O

O

CH2 HO

I I I

I

HN CH CH2

C

O

O

CH2

I I

I OH

I

I- + H2O2 I- + H2O2

I-

Iodine: thyroid hormone

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Prevention of diseases Vascular diseases: Vitamin B 6, 12, folic acid

Dementia: Vitamin B 6, 12, folic acid

Osteoporosis: Vitamin A, D, K