911 Reactions Block 3 Flashcards

15863654960	Hi you're doing great and everything is going to be fine		0
15863654961	Ether		1
15863735680	Epoxide		2
15863741509	Acetal		3
15863751072	Thioester		4
15863752887	Sulfoxide		5
15863755051	Sulfone		6
15863757957	N-oxide		7
15863759379	Nitrile		8
15863763163	Carboxamides		9
15863767077	Carboxy ester		10
15863771224	Phase 1 Metabolism Purpose	To introduce functional groups needed for phase 2 processing	11
15863785742	Phase 2 Metabolism Purpose	To increase hydrophilicity of drugs / metabolites to promote excretion	12
15863797750	When would something be protonated?	pH < pKa	13
15863800875	When would something be deprotonated?	pH > pKa	14
15863810513	General CYP reaction	1. NADPH 2. Reductase 3. CYP 4. O2	15
15863858370	Privileged Positions	1. Benzylic carbon 2. Allylic carbon 3. Carbon alpha to carbonyl 4. Carbon alpha to heteroatom 5. Aryl carbon 6. Carbon-carbon double bonds 7. Nitrogen-center 8. Sulfur-center	16
15863872230	Benzylic carbon		17
15863875621	Allylic carbon		18
15863891150	Carbon alpha to carbonyl		19
15863895023	Carbon alpha to heteroatom		20
15863926205	Aryl carbon	Carbon ortho/para to EDG	21
15863941142	2 general steps of CYP oxidation reaction	1. Insertion of an oxygen atom 2. Fragmentation of a drug	22
15863946435	Enantiomers	isomers that are mirror images of each other	23
15863950608	Diastereomers	stereoisomers that are not mirror images	24
15863957940	Racemic mixture	A mixture that contains equal amounts of the (+) and (-) enantiomers. Racemic mixtures are not optically active.	25
15864005890	What oxidation reactions can CYPs complete?	Hydroxylation of alkanes oxidation of primary alcohols oxidation of secondary alcohols hydroxylation of arenes oxidation of alkanes and alkenes oxidation of nitrogen compounds oxidation of sulfur compounds	26
15864045427	CYP hydroxylation of alkanes	Alkane —> alcohol	27
15864067844	CYP oxidation of primary alcohols	Primary alcohol —> aldehyde —> carboxylic acid	28
15864078998	CYP hydroxylation of arenes	Arenes —> phenol (ortho/para to EDGs)	29
15864090815	Common EDGs	NH2 OH OCH3 C6H5	30
15864107000	CYP oxidation of alkanes and alkenes	Alkane —> alkene —> epoxide	31
15864110103	CYP oxidation of tertiary amines	Tertiary amines —> N-oxide	32
15864254390	CYP oxidation of secondary amines	Secondary amine —> N-hydroxlamines	33
15864285268	N-hydroxylamines		34
15864290021	CYP oxidation of primary amines	Primary amine —> nitroso compounds (toxic)	35
15864306059	CYP oxidation of sulfide	Sulfide —> sulfoxide	36
15864309552	CYP oxidation of sulfoxide	Sulfoxide —> sulfone	37
15864316790	What are the different oxidation-fragmentation reactions?	Dehalogenation Deamination Dealkylation Dehydrogenation	38
15864343275	CYP dehalogenation of primary alkyl halide	Primary alkyl halide —> aldehyde	39
15864347915	CYP dehalogenation of secondary alkyl halide	Secondary alkyl halide —> ketone	40
15864355203	Do tertiary alkyl halides under CYP oxidation?	No	41
15864357762	CYP oxidation of dihalides	Dihalide —> acid halide (toxic)	42
15864379657	CYP deamination of primary amine	Primary amine —> aldehyde	43
15864383330	CYP deamination of secondary amine	Secondary amine —> ketone	44
15864389751	CYP dealkylation	Loss of an alkyl group Hemiacetyl intermediate products: alcohol and aldehyde (biproduct)	45
15864406867	CYP dehydrogenation	Loss of 2 H+ Products: quinone and pyridines (toxic)	46
15864423061	4 most important CYPs	CYP3A4/5/7 CYP2D6 CYP2C9 CYP1A/1/2	47
15864470300	4 CYPs most susceptible to SNPs	CYP3A4/5/7 CYP2D6 CYP2C9 CYP1A/1/2	48
15864496285	FMOs reactions	Oxidize drugs with nitrogen, sulfur, and phosphorous groups	49
15864506346	FMO N-oxidation	Nitrogen oxidation	50
15864509120	FMO S-oxidation	Sulfur oxidation	51
15864512896	What do FMOs rely on?	FAD-OOH	52
15864513621	FAD-OOH		53
15864548504	What is the predominant FMO?	FMO3	54
15864559093	FMO Thioether oxidation	Thioether —> sulfoxides and sulfones	55
15864608903	Peroxidases	Their job is to catalyze metabolic reactions that release Hydrogen Peroxide (H2O2) which is toxic to cells.	56
15864637368	Peroxidase example	Catalase	57
15864645862	Alcohol dehydrogenase (ADH) reactions	Oxidize primary alcohols oxidize secondary alcohols reduce carbonyl groups	58
15864675563	ADH Primary alcohol oxidation	Primary alcohol —> aldehyde	59
15864702446	ADH secondary alcohol oxidation	Secondary alcohol —> ketone	60
15864716666	ADH carbonyl reduction	Ketone —> secondary alcohol aldehyde —> primary alcohol	61
15864722664	When would ADH need NAD+?	When oxidizing an alcohol	62
15864724957	When would ADH need NADH?	When reducing a carbonyl	63
15864733409	Is ADH reversible?	Yes - the only one that is	64
15864737644	Aldehyde dehydrogenase (ALDH) reaction	Aldehyde —> carboxylic acid	65
15864776051	What is ALDH dependent on?	NAD+	66
15864819420	Aldehyde oxidase (AO) reactions	1. Oxidizes aldehydes 2. Oxidized nitrogen-containing heterocycles	67
15864824442	AO aldehyde oxidation	Aldehyde + H2O + O2—> carboxylic acid + H2O2	68
15864838168	AO nitrogen-containing heterocyclic oxidation	Oxidation occurs at alpha carbon to N	69
15864859004	What does AO depend on?	O2 and H2O	70
15864862527	Xanthine oxidase (XO) reaction	Hypoxanthine + H2O + O2—> xanthine + H2O2—> Uric acid + H2O2	71
15864881625	What does XO depend on?	H2O and O2	72
15864885613	How does AO differ from ALDH?	With AO, electrons are transferred to an oxygen With ALDH, electrons are transferred to NAD+	73
15864897091	MAOs reactions	Oxidation of amines (primary, secondary, and tertiary)	74
15864907270	What is MAOs dependent on?	FAD	75
15864921103	MAO primary amine oxidation	Primary amine —> imine —(ox. deamination)—> aldehyde	76
15864958461	Imine		77
15864969142	Oxidative deamination	Imine —> aldehyde	78
15864976565	Flavin-based reductases (FR)	Reduce drugs and metabolites by handing the electron directly to the drug or molecule	79
15864984807	What are FRs dependent on?	NADPH	80
15864987082	Carbonyl reductases (CR) reaction	Carbonyl —> alcohol	81
15864999683	What is CR dependent on?	NADPH	82
15865004378	How do ADH and CR differ?	ADH is reversible and CR is not	83
15865007068	Azo reductases (AR) reaction	N=N —> hydrazine —> anilines	84
15865045101	Aniline		85
15865048155	Hydrazine		86
15865056757	What does AZ require	NADPH or NADH	87
15865060171	Nitro reductases (NR) reaction	Nitro group(NO2) —> N=O —> amine (NH2)	88
15865084203	What does NR require?	NADPH or NADH	89
15865088895	Carboxyesterases (CE) reaction	Carboxylic ester —> alcohol and carboxylate	90
15865118405	Phase 2 conjugation reactions	Glucuronidation Sulfination Glutathione Acetylation Amino Acid	91
15865132403	Glucuronidation enzyme	UGT	92
15865134669	UGT reaction	Attaches a glucuronate to drugs and metabolites	93
15865136348	Glucuronate		94
15865146939	Do UGTs have a broad or narrow specificity?	Broad	95
15865155421	What is the most important phase 2 enzyme?	UGT	96
15865160316	Functional groups UGTs act on?	Alcohols thiols amines carboxylic acids carboxamides	97
15865179783	O-glucuronidation	Adds glucuronate to alcohol or carboxylic acid	98
15865185988	N-glucuronidation	Adds glucuronate to amines	99
15865199516	S-glucuronidation	Adds glucuronate to thiol	100
15865201544	C-glucuronidation	Adds glucuronate to hydrocarbon group	101
15865220837	Are UGTs present at birth?	No	102
15865239466	Sulfation Enzyme	STs	103
15865248132	STs reaction	Adds SO3 onto drugs and metabolites	104
15865259382	What functional groups do STs work on?	Aromatic alcohols, primary and secondary alcohols, aryl amines, and N-hydroxyamines	105
15865265296	In what people are STs favorable?	Children	106
15865269990	Glutathione structure		107
15865281489	Glutathione (GSH) reaction	Adds glutathione to toxic drugs and metabolites to make them mercapturic acids	108
15865286770	Favism	Reduced level of NADPH affects glutathione levels and leaves RBCs vulnerable to oxidizing agents	109
15865313212	Acetylation enzyme	NATs	110
15865313213	What do NATs require?	Acetyl-CoA	111
15865318415	What do STs require?	An activated form of sulfate (PAPs)	112
15865329129	What do UGTs require?	UDP-Glucuronate	113
15865332635	NATs reaction	Adds an acetyl group to N-H bonds	114
15865352478	Acetyl group		115
15865359553	Amino acid conjugation enzyme	NACTs	116
15865361326	NACTs reaction	Couple a CoA-activated drug/metabolite to an amino acid	117
15865367696	Which amino acid is typically conjugated to drugs / metabolites by NACTs ?	Gly	118
15865371411	Toxic metabolites	Iminoquinones epoxides acid chlorides nitroso compounds	119
15865378547	Nitroso compound		120