* Vitamin/ Mineralaging.pharm.pusan.ac.kr/lab/lecture/2011_2/L1 수정 2011... · 2011-10-25 · 1)...
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Transcript of * Vitamin/ Mineralaging.pharm.pusan.ac.kr/lab/lecture/2011_2/L1 수정 2011... · 2011-10-25 · 1)...
* 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
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
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)
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
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)
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)
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)
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
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
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
간
*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
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
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
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
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
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
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
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
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
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
Prevention of diseases Vascular diseases: Vitamin B 6, 12, folic acid
Dementia: Vitamin B 6, 12, folic acid
Osteoporosis: Vitamin A, D, K