Enzyme酵素/酶/鋂

主條目:生化學

catalyst of biochemical reaction(metabolism)生化(新陳代謝) 反應的催化劑

can be classified into 6 kinds according to IUBMB根據IUBMB可以分成六大類

IUBMB enzyme classification[]

===1.oxidoreductase===

~oxidase

~reductase

~dehydrogenase(deHase)

Ex. Alcohol deHase

常以

NAD+(oxidation)

NADPH(reduction)

as coenzyme

~perosidase

Peroxisome中有peroxidase(過氧化酶)、catalase(過氧化氫酶)，和ER一樣可以解alc之毒:

peroxidase(過氧化酶):把反應物的氫移到氧上使反應物過氧化並且產生過氧化氫H2O2

glyoxysome(乙醛酸循環體)，植物中特有的胞器，可以使用脂質形成醣類，不像動物無法以脂質形成醣類，動物只能靠糖質新生形成醣類。和peroxisome一樣皆司氧化。兩者合稱microbody(微體)

*microsome(微粒體)不是胞器，是細胞

均質化之後離心所得到三層中的一層。主要是由胞器中的sER(平滑型內質網)所形成。微粒體含有細胞色素P450（CYP）酶，與氧化代謝有關。

上層: microsome(微粒體)	microsome(微粒體) (1/3)
中層:可溶性	非microsome(微粒體) (2/3)
下層:粒線體	非microsome(微粒體) (2/3)

catalase(過氧化氫酶) :

使過氧化氫H2O2變成H2O+O2

===2.transferase===

~kinase

(but thiokinase (form C-S) is class 6)

receptor tyrosin kinase

tyrosin kinase

cytoplasmic pt. kinase

常serine/threonine kinase

Ex. PKA

But JAK kinase為tyrosin kinase

*protein kinase(蛋白激酶

*細胞中一直存在cdk(cyclin-dependent kinase)。而濃度不一定的cyclin(週期素)，有時存在，有時消失，cyclin(週期素)和cdk(cyclin-dependent kinase)形成cyclin/cdk complex促使細胞週期的進行

~tansferase

Ex. PEP carboxykinase?

trans~ ~ase

===3.hydrolase 水解酶(need H2O)===

~hydrolase ~水解酶

*Lysosome中有hydrase(水解酶):可以把水拆成H和OH加到被分成兩半的反應物中

~esterase ~酯酶

~phosphatase 磷酸酶

*protein phosphatase(蛋白質磷酸酯酶)

lipase脂解酶

amylase 澱粉酶

~glycosidase ~糖苷酶

~peptidase ~胜肽酶

~protease ~蛋白水解酶

caspase 自劊蛋白CED-3

~protinase ~蛋白酶

pepsin胃蛋白酶

need acidic condition

trypsin胰蛋白酶

need basic condition

chymotrypsin胰凝乳蛋白酶

elastase彈性酶

urease尿素酶

*Separase(分離酶)展現活性而水解cohesin

exonucleases

大多數的DNA polymerase有3’→5’的核酸外切酶活性(DNA polymeraseβ例外)，所以可以邊合成DNA邊校正

*內部的限制性核酸內切酶(restriction endonucleases，簡稱限制酵素(restriction enzyme))

，可以認識並切斷外來的DNA，是細菌防禦噬菌體的機制。如果在酶可以切的位置(restriction site)加上甲基，限制酶就無法切。Biotechnology(生物科技)中所用的restriction enzyme就是這個enzyme。

*repetitive sequence中highly repetitive sequence的Alu命名來自可以被Alu I( a restriction enzyme)切

===4.lyase解離酶 (need H2O or not)(addition to C=C)===

carbonylanhydrase

fumarse

aldolase

===5.isomerase===

racemase消旋酶&epimerase表異構酶

act on carbohydrates

cis-trans isomerase

L←→D

===6.ligase結合酶/連結酶(need ATP)===

~synthase

~synthetase

~thiokinase (form C-S)

carboxylase (form C-C (羧化酶))

thiamine (B1) as cofactor

*Anaphase(後期) 促進複合體APC(anaphase promoting complex)為一種ubiqutin ligase，開始活化以水解securin(緊固蛋白)

*DNA ligase

*Glycogen phosphorylase肝醣磷酸化酶

EC 1 Oxidoreductases氧化還原酶[]

.

EC 2 Transferases轉移酶/kinase 激酶[]

.

EC 3 Hydrolases水解酶[]

.

EC 4 Lyases裂解酶[]

.

EC 5 Isomerases異構酶[]

.

EC 6 Ligases連結酶[]

.

藥品代謝[]

Drug metabolism(Drug Biotransformation):exobiotics(外生性物質)在體內經過各器官代謝的現象稱作first-pass metabolism(首渡效應)。不同exobiotics經過一個或多個不同的器官進行代謝，因此不同的器官出問題時，會對依賴其代謝的exobiotics產生影響(血中濃度上升或是下降)。主要發生在肝臟，另外對口服藥而言，腸常常也是一個重要的代謝位置。人家說肝臟能”解毒”是因為肝臟藉由phase I和phase II的反應增加藥物的極性，使之能從腎臟排泄。所以事實上肝臟做的是”增加極性”，而不是”解毒”，因此有些藥物經過肝臟代謝後反而活性增強或是產生毒性[]

phase I:

加上或是使露出-OH、-NH2或是-SH等nucleophile的基團，增加親水性使之能從腎臟排泄

microsomal hydroxylase

=cytochrome P450 monooxgenase enzyme system細胞色素P450單氧化酵素系統

=mixed-function oxidase(MFO)

1. NADPH-cytochrome P450 reductase

a flavoprotein

=P450 reductase

和下面比起來較少，所以是速率決定步驟

2. cytochrome P450

=P450

=CYP

an oxidase

an hemeprotein

和上面比起來較多，所以不是速率決定步驟

1. Peroxidase and other monooxygenase為hemeprotein

2. Phosphatydyl choline為phospholipid促進由P450 reductase到P450的電子轉移

cytochrome P450-independent oxidation

reduction

hydrolysis

NADPH-cytochrome P450 reductase

a flavoprotein

=P450 reductase

和下面比起來較少，所以是速率決定步驟

?

cytochrome P450

=P450

=CYP

an oxidase

an hemeprotein

和上面比起來較多，所以不是速率決定步驟

cytochrome P450-dependent oxidation

*aromatic hydroxylations

*aliphatic hydroxlations

*epoxidation(環氧化)

*oxidative dealkylation:

N-dealkylation

O -dealkylation

S -dealkylation

*N-oxidation

primary amine

secondary amine

tertiary amine

*S-oxidation

*oxidative deamination(氧化脫胺作用)

*desulfuration

*dechlorination

cytochrome P450-independent oxidation

*flavin monooxygenase(FMO)

(Ziegler’s enzyme)

*amine oxidases

*dehydrogenations

*oxidation of alc(Foye)

*aldehyde dehydrogenase(Foye)

*Molybdenum hydroxylases(Foye)

**aldehyde oxidase

**xanthine oxidase

**xanthine hydrogenase

*oxidative deamination of amines(Foye)

**Monoamine oxidase(MAO)

(單胺氧化酶)

**diamine oxidase

(雙胺氧化酶)

*β-oxidation(Foye)

*hydrolysis(Foye)

reduction

*azo reductions(偶氮還原)

*nitro reductions(硝基還原)

*carbonyl reductions(羰ㄊㄢˋ基還原)

hydrolysis

*esters(酯)

*amides(醯胺)

phase II:

conjugation(抱合反應):加上一些親水性的大基團，唯一的例外是acetylation(乙醯化反應)

glucuronic acid conjugation(葡萄糖醛酸抱合反應):因為glucuronic acid是單醣的一種，所以此反應事實上和植物形成glycoside(配糖體)是相同的意義，是人體內的配糖體形成反應

因為是配糖體形成的反應，所以是用-OH而不是用-COOH進行反應。

所以drug有-COOH時才有酯

UDP-glucuronosyl transferase (UGT) 1 and 2

sulfate conjugation(硫酸抱合反應):將藥物的nucleophilic gr.和sulfate形成硫酸酯?

conjugation with AA

main substrate為-COOH

conjugation with CoA(thiol硫醇)

acetylation(乙醯化)

phase II後水溶性變低的例外

main substrate為-NH2

Glutathione conjugation(榖胱甘肽抱合反應) & mercapturic acid synthesis

利用Glutathione(榖胱甘肽)的-SH(nucleophile)去攻打electrophile?

methylation:O、N、thiol

phase II後水溶性變低的例外

conjugation of cyanide

以下為P450的分類和其在體內本來的作用(通常都是製造像是steroid hormone、cholesterol、active Vit D congener and bile acid的酶signaling molecule(內分泌和NT)個論中的steroid hormone。參考本書)。較重要者以框框框起來，其中CYP3A4占30%的物質代謝。

Family	Function	Members	Names
CYP1	drug and steroid (especially estrogen) metabolism	3 subfamilies, 3 genes, 1pseudogene	CYP1A1, CYP1A2, CYP1B1
CYP2	drug and steroidmetabolism	13 subfamilies, 16 genes, 16pseudogenes	CYP2A6, CYP2A7, CYP2A13, CYP2B6, CYP2C8,CYP2C9, CYP2C18, CYP2C19, CYP2D6, CYP2E1,CYP2F1, CYP2J2, CYP2R1, CYP2S1, CYP2U1,CYP2W1
CYP3	drug and steroid(includingtestosterone) metabolism	1 subfamily, 4 genes, 2pseudogenes	CYP3A4, CYP3A5, CYP3A7, CYP3A43
CYP4	arachidonic acid or fatty acid metabolism	6 subfamilies, 12 genes, 10pseudogenes	CYP4A11, CYP4A22, CYP4B1, CYP4F2, CYP4F3,CYP4F8, CYP4F11, CYP4F12, CYP4F22, CYP4V2,CYP4X1, CYP4Z1
CYP5	thromboxane A₂synthase	1 subfamily, 1 gene	CYP5A1
CYP7	bile acidbiosynthesis 7-alpha hydroxylase of steroid nucleus	2 subfamilies, 2 genes	CYP7A1, CYP7B1
CYP8	varied	2 subfamilies, 2 genes	CYP8A1 (prostacyclin synthase), CYP8B1 (bile acid biosynthesis)
CYP11	steroid biosynthesis	2 subfamilies, 3 genes	CYP11A1, CYP11B1, CYP11B2
CYP17	steroid biosynthesis, 17-alpha hydroxylase	1 subfamily, 1 gene	CYP17A1
CYP19	steroid biosynthesis:aromatasesynthesizesestrogen	1 subfamily, 1 gene	CYP19A1
CYP20	unknown function	1 subfamily, 1 gene	CYP20A1
CYP21	steroid biosynthesis	2 subfamilies, 1 gene, 1 pseudogene	CYP21A2
CYP24	vitamin Ddegradation	1 subfamily, 1 gene	CYP24A1
CYP26	retinoic acidhydroxylase	3 subfamilies, 3 genes	CYP26A1, CYP26B1, CYP26C1
CYP27	varied	3 subfamilies, 3 genes	CYP27A1 (bile acid biosynthesis), CYP27B1 (vitamin D₃1-alpha hydroxylase, activates vitamin D₃), CYP27C1(unknown function)
CYP39	7-alpha hydroxylation of 24-hydroxycholesterol	1 subfamily, 1 gene	CYP39A1
CYP46	cholesterol 24-hydroxylase	1 subfamily, 1 gene	CYP46A1
CYP51	cholesterolbiosynthesis	1 subfamily, 1 gene, 3 pseudogenes	CYP51A1 (lanosterol 14-alpha demethylase)

輔因子(cofactor)[]

每一步驟酵素的作用機轉，解釋了生物學中的酵素如何作用。維生素和礦物質的作用原理就常常是酵素的輔因子。

Pt and enzyme
name	Cofactor(輔因子		功用
name	Atom group binding covalently to Pt. ( being called prosthetic group(輔效基) in enzyme )	Atom group binding non-covalently to Pt. ( being called coenzyme(輔酶) in enzyme )	功用
kinase	Mg2+		Enzyme
Catalase(過氧化氫酶	Fe2+/Fe3+		enzyme
Myoglobin(肌紅素	一個Fe2+		O2 carrier ( storage )
Hemoglobin(血紅素	四個Fe2+、heme		O2 carrier ( transporter )

flavoprotein	FMN(flavin mononucleoside)		e- carrier
flavoprotein	FAD(flavin adenine dinucleotide)		e- carrier
iron-sulfur pt.	iron and sulfur		e- carrier
coenzyme Q (ETC中唯一非蛋白質者)		ubiquinone(Co Q) (coenzyme Q)	e- carrier
cytochrome	Heme with Fe2+		e- carrier
cytochrome	必有Fe
Cytaa3	Cu
Monoamine oxidase MAO flavoprotein		Vit B2	enzyme
dehydrogenase		VitB3 NADP+ or NAD+	enzyme
AA decarboxylase dopa decarboxylase 5HT decarboxylase		Vit B6: pyridoxine(吡)	enzyme
carboxylase(羧化酶) (form C-C)		Vit B1(thiamine as cofactor)	enzyme
microsomal hydroxylase =cytochrome P450 monooxgenase enzyme system細胞色素P450單氧化酵素系統 =mixed-function oxidase(MFO) NADPH-cytochrome P450 reductase a flavoprotein =P450 reductase 和下面比起來較少，所以是速率決定步驟	1 FMN(flavin mononucleoside)+ 1 FAD(flavin adenine dinucleotide)	NADPH	enzyme
microsomal hydroxylase =cytochrome P450 monooxgenase enzyme system細胞色素P450單氧化酵素系統 =mixed-function oxidase(MFO) cytochrome P450 =P450 =CYP an oxidase an hemeprotein 和上面比起來較多，所以不是速率決定步驟	Heme with Fe2+		enzyme

Enzyme cofactors
Active forms	vitamins	TPP / ThDP (B₁)
		FMN, FAD (B₂)
		NAD⁺, NADH, NADP⁺, NADPH (B₃)
		Coenzyme A (B₅)
		PLP / P5P (B₆)
		Biotin (B₇)
		THFA / H₄FA, DHFA / H₂FA, MTHF(B₉)
		AdoCbl, MeCbl (B₁₂)
		Ascorbic Acid (C)
		Phylloquinone (K₁)
		Menaquinone (K₂)
		Coenzyme F420
	non-vitamins	ATP · CTP
		SAMe
		PAPS
		GSH
		Coenzyme B · Cofactor F430 · Coenzyme M · Coenzyme Q
		Heme / Haem (A, B, C, O)
		Lipoic Acid
		Methanofuran
		Molybdopterin/Molybdenum cofactor
		PQQ
		THB / BH₄
		THMPT / H₄MPT
	minerals	Ca²⁺ · Cu²⁺ · Fe²⁺, Fe³⁺ · Mg²⁺ · Mn²⁺ · Mo · Ni²⁺ · Se · Zn²⁺
Base forms	vitamins: see vitamins
M: NUT	cof, enz, met	noco, nuvi, sysi/epon, met

Vitamins and derivatives[]

Cofactor	Vitamin	Additional component	Chemical group(s) transferred	Distribution
Thiamine pyrophosphate	Thiamine (B₁)	None	2-carbon groups, α cleavage	Bacteria, archaea and eukaryotes
NAD⁺ and NADP⁺	Niacin (B₃)	ADP	Electrons	Bacteria, archaea and eukaryotes
Pyridoxal phosphate	Pyridoxine (B₆)	None	Amino and carboxyl groups(西101)	Bacteria, archaea and eukaryotes
Lipoamide	Lipoic acid	None	electrons, acyl groups	Bacteria, archaea and eukaryotes
Methylcobalamin	Vitamin B₁₂	Methyl group	acyl groups	Bacteria, archaea and eukaryotes
Cobalamine	Cobalamine (B₁₂)	None	hydrogen, alkyl groups	Bacteria, archaea and eukaryotes
Biotin	Biotin (H)	None	CO₂	Bacteria, archaea and eukaryotes
Coenzyme A	Pantothenic acid (B₅)	ADP	Acetyl group and other acyl groups	Bacteria, archaea and eukaryotes
Tetrahydrofolic acid	Folic acid (B₉)	Glutamate residues	Methyl, formyl, methylene and formimino groups	Bacteria, archaea and eukaryotes
Menaquinone	Vitamin K	None	Carbonyl group and electrons	Bacteria, archaea and eukaryotes
Ascorbic acid	Vitamin C	None	Electrons	Bacteria, archaea and eukaryotes
Flavin mononucleotide	Riboflavin (B₂)	None	Electrons	Bacteria, archaea and eukaryotes
Flavin adenine dinucleotide	Riboflavin (B₂)	None	Electrons	Bacteria, archaea and eukaryotes
Coenzyme F420	Riboflavin (B₂)	Amino acids	Electrons	Methanogens and some bacteria

Non-vitamins[]

Cofactor	Chemical group(s) transferred	Distribution
Adenosine triphosphate	Phosphate group	Bacteria, archaea and eukaryotes
S-Adenosyl methionine	Methyl group	Bacteria, archaea and eukaryotes
Coenzyme B	Electrons	Methanogens
Coenzyme M	Methyl group	Methanogens
Coenzyme Q	Electrons	Bacteria, archaea and eukaryotes
Cytidine triphosphate	Diacylglycerols and lipid head groups	Bacteria, archaea and eukaryotes
Glutathione	Electrons	Some bacteria and most eukaryotes
Heme	Electrons	Bacteria, archaea and eukaryotes
Methanofuran	Formyl group	Methanogens
Molybdopterin	Oxygen atoms	Bacteria, archaea and eukaryotes
Nucleotide sugars	Monosaccharides	Bacteria, archaea and eukaryotes
3'-Phosphoadenosine-5'-phosphosulfate	Sulfate group	Bacteria, archaea and eukaryotes
Pyrroloquinoline quinone	Electrons	Bacteria
Tetrahydrobiopterin	Oxygen atom and electrons	Bacteria, archaea and eukaryotes
Tetrahydromethanopterin	Methyl group	Methanogens

Ion	Examples of enzymes containing this ion
Cupric	Cytochrome oxidase
Ferrous or Ferric	Catalase Cytochrome (via Heme) Nitrogenase Hydrogenase
Magnesium	Glucose 6-phosphatase Hexokinase DNA polymerase
Manganese	Arginase
Molybdenum	Nitrate reductase Nitrogenase
Nickel	Urease
Selenium	Glutathione peroxidase
Zinc	Alcohol dehydrogenase Carbonic anhydrase DNA polymerase

藥品[]

LYSOZYME
- 複方:Cotazym膠囊／每Cap含有：
  - DEXTROMETHORPHAN HBR 20.0MG;
  - LYSOZYME CHLORIDE(POTENCY)20MG;
  - POTASSIUM CRESOLSULFONATE 90.0MG
- 用法用量:可用於鎮咳、祛痰一天3次，每次1粒。糖漿一次量：大人4~6ml。
南光BROEN-C ENTERIC F.C. TABLETS "N.K.":適應症手術後及外傷後腫脹之緩解、副鼻腔炎、乳房鬱積、呼吸器疾患隨伴喀痰喀出困難、氣管內麻醉後之喀痰喀出困難、痔核

延伸學習[]

prosthetic group and coenzyme