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'UĈѭӡQJ 7Kӏ+ӗQJ'LӋS
ƌ͘ƵŽŶŐdŚŝ,ŽŶŐŝĞƉ ϭ
0өFWLrX
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ƌ͘ƵŽŶŐdŚŝ,ŽŶŐŝĞƉ Ϯ
'jQEjL
, 3KҫQ,++SURWLG
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ƌ͘ƵŽŶŐdŚŝ,ŽŶŐŝĞƉ ϯ
ĈҥL FѭѫQJ
‡ 3URWHLQ
± Oj WS NK{QJ WKӇ WKLӃX FӫD 7%Yj Fѫ WKӇ VӕQJ
± Oj QJXrQ OLӋX FҫQ WKLӃW WәQJ KӧS QKӳQJ WSFҩX WU~F FӫD
Fѫ WKӇ
± /j HQ]PH
± y NKҧ QăQJ JҳQ NӃW YӟL
‡ /LSLGJOXFLGSURWHLQNKiF
‡ .LPORҥLiNLP
‡ 3URWHLQ
± y WUӑQJ OѭӧQJ SKkQ Wӱ FDR
± /j SROSHSWLGHQKLӅX DD ONYӟL QKDX EҵQJ ONSHSWLGH
± 7URQJ WSFW Fy+21Yj 63
‡ 3KkQ ELӋW
± $FLGDPLQ DD
Oj ÿѫQ Yӏ FҩX WҥR QKӓ QKҩW FӫD SURWHLQ
± 3HSWLGHOj SW JӗP ÿӃQ ”DD
± 3URWHLQOj SW JӗP •ÿӃQ •DDFy FҩX WU~F SKӭF
WҥS
+H/D FHOOVZLWKSURWHLQV
ODEHOHGLQEOXHDQG'1$LQUHG ϰ
'U'XRQJ7KL+RQJ'LHS
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ƌ͘ƵŽŶŐdŚŝ,ŽŶŐŝĞƉ ϱ
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ƌ͘ƵŽŶŐdŚŝ,ŽŶŐŝĞƉ ϲ
ĐŝĚĂŵŝŶ
‡ /j VS WKӫ SKkQ FXӕL FQJ FӫD
SHSWLG Yj SURWHLQ
‡ y ORҥL DD WKѭӡQJ JһS
± ѫ WKӇ 7+ÿѭӧF PӝW YjL ORҥL DD
± ѫ WKӇ NK{QJ 7+ÿѭӧF PӝW YjL
ORҥL DD ĺFXQJ FҩS Wӯ 7ĂDD WKLӃW
ӃX
‡ 1JRjL UD FzQ PӝW Vӕ DD tW JһS
± y WURQJ WSFW FӫD SURWHLQ
± .K{QJ Fy WURQJ WSFW FӫD SURWHLQ
‡ 'ҥQJ NӃW KӧS
‡ 'ҥQJ Wӵ GR ϳ
'U'XRQJ7KL+RQJ'LHS
1KX FҫX WӕL WKLӇX FiF DD ӣQJѭӡL
ϴ
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,ҩX WҥR KyD KӑF FӫD DD
‡ 5JӕF KGURFDUERQULrQJ FKR
WӯQJ DD
‡ FKXQJ FKR WҩW Fҧ FiF DD
± 1KyP FDUER[O±22+
± 1KyP DPLQ±1+
± QJ JҳQ YjR FDUERQĮ
‡ +ҫX KӃW DD WURQJ Wӵ QKLrQ WKXӝF
ORҥL/ĮDPLQ
‡ Į FDUERQĮ
ϵ
'U'XRQJ7KL+RQJ'LHS
iFK ÿiQK Vӕ WKӭ Wӵ FDUERQ
ϭϬ
'U'XRQJ7KL+RQJ'LHS
,3KkQ ORҥL
‡ 7 WKHR JӕF 5DD ÿѭӧF FKLDOjP ORҥL
± $D PҥFK WKҷQJFKLDOjP QKyP
‡ $D WUXQJ WtQK DFLGPRQRDPLQ PRQRFDUER[OLF
‡ $FLGDPLQ DFLGDFLGPRQRDPLQ GLFDUER[OLF
‡ $FLGDPLQ NLӅP DFLGGLDPLQ PRQRFDUER[OLF
± $D PҥFK YzQJORҥL FKtQK
‡ $FLGDPLQ Fy QKkQ WKѫP
‡ $FLGDPLQ FKӭD Gӏ YzQJ
ϭϭ
'U'XRQJ7KL+RQJ'LHS
,'DQKSKiS 3KkQORҥLWW
677 6ӕ  7rQ WK{QJ GөQJ Yj
Nê KLӋX FKӳ Yj 
FKӳ
7rQ KyD KӑF
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*
$FLGĮDPLQRDFHWLF
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$
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/
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PHWOYDOHULF
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5Oj FKXӛL
KGURFDUERQQR
ϭϮ
'U'XRQJ7KL+RQJ'LHS
,'DQKSKiS 3KkQORҥLWW
//͘Ϯ͘ϭ͘ϭ͘ĐŝĚĂŵŝŶ ƚƌƵŶŐ ƚşŶŚ ;ĂĐŝĚŵŽŶŽĂŵŝŶ ŵŽŶŽĐĂƌďŽdžLJůŝĐͿ
^dd ^Һ  dġŶ ƚŚƀŶŐ ĚӅŶŐ ǀă Ŭlj
ŚŝҵƵ ;ϯĐŚӋ ǀă ϭĐŚӋͿ
dġŶ ŚſĂ ŚҸĐ
ϲ ϯ ^ĞƌŝŶ ;^ĞƌͿ;^Ϳ ĐŝĚɲͲĂŵŝŶŽɴͲ
ŚLJĚƌŽdžLJ ƉƌŽƉŝŽŶŝĐ
ϳ ϰ dŚƌĞŽŶŝŶ ;dŚƌͿ;dͿ ĐŝĚɲͲĂŵŝŶŽɴͲ
ŚLJĚƌŽdžLJ ďƵƚLJƌŝĐ
ϴ ϯ LJƐƚĞŝŶ ;LJƐͿ ;Ϳ ĐŝĚɲͲĂŵŝŶŽɴͲƚŚŝŽů
ƉƌŽƉŝŽŶŝĐ
ϵ ϱ DĞƚŚŝŽŶŝŶ ;DĞƚͿ;DͿ ĐŝĚɲͲĂŵŝŶŽ ɶͲ
ŵĞƚLJůƚŚŝŽͲŶͲďƵƚLJƌŝĐ
ZĐſ ĐŚӈĂ ŶŚſŵ
ͲK,
ZĐſ ĐŚӈĂ Ͳ^
ϭϯ
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,'DQKSKiS 3KkQORҥLWW
,,$FLGDPLQ DFLGDFLGPRQRDPLQ GLFDUER[OLF
y KRһF QKyP DPLQ Yj QKyP FDUER[O
^dd ^Һ  dġŶ ƚŚƀŶŐ ĚӅŶŐ ǀă Ŭlj
ŚŝҵƵ ;ϯĐŚӋ ǀă ϭĐŚӋͿ
dġŶ ŚſĂ ŚҸĐ
ϭϬ ϰ ĐŝĚĂƐƉĂƌƚŝĐ;ƐƉͿ;Ϳ ĐŝĚɲͲĂŵŝŶŽƐƵĐĐŝŶŝĐ
ϭϭ ϰ ƐƉĂƌĂŐŝŶ ;ƐŶͿ;EͿ ɶͲĂŵŝĚĐӆĂ ĂĐŝĚ
ĂƐƉĂƌƚŝĐ
ϭϮ ϱ ĐŝĚŐůƵƚĂŵŝĐ;'ůƵͿ ;Ϳ ĐŝĚɲͲĂŵŝŶŽŐůƵƚĂƌŝĐ
ϭϯ ϱ 'ůƵƚĂŵŝŶ ;'ůŶͿ;YͿ ɶͲĂŵŝĚĐӆĂ ĂĐŝĚ
ŐůƵƚĂŵŝĐ
ϭϰ
'U'XRQJ7KL+RQJ'LHS
,,'DQKSKiS 3KkQORҥLWW
^dd ^Һ  dġŶ ƚŚƀŶŐ ĚӅŶŐ ǀă Ŭlj
ŚŝҵƵ ;ϯĐŚӋ ǀă ϭĐŚӋͿ
dġŶ ŚſĂ ŚҸĐ
ϭϰ ϲ LJƐŝŶ ;LJƐͿ;Ϳ ĐŝĚɲ͕ɸͲĚŝĂŵŝŶŽ ŶͲ
ĐĂƉƌŽŝĐ
ϭϱ ϲ ƌŐŝŶŝŶ ;ƌŐͿ;ZͿ ĐŝĚɲͲĂŵŝŶŽɷͲ
ŐƵĂŶŝĚŽͲŶǀĂůĞƌŝĐ
//͘Ϯ͘Ϯ͘ ĐŝĚĂŵŝŶ ŵҢĐŚ ǀžŶŐ ĐŝĚ ĂŵŝŶ Đſ ŶŚąŶ
ƚŚҿŵ
ϭϲ ϵ WŚĞŶLJůĂůĂŶŝŶ ;WŚĞͿ ;Ϳ ĐŝĚɲͲĂŵŝŶŽɴͲ
ƉŚĞŶLJůƉƌŽƉŝŽŶŝĐ
ϭϳ ϵ dLJƌŽƐŝŶ ;dLJƌͿ;zͿ ĐŝĚɲͲĂŵŝŶŽɴͲ;ʌͲ
ŚLJĚƌŽdžLJƉŚĞŶLJůͿ
ƉƌŽƉŝŽŶŝĐ
,,$FLGDPLQ NLӅPDFLGGLDPLQ PRQRFDUER[OLF
y QKyP DPLQ Yj QKyP FDUER[O
ϭϱ
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,,'DQKSKiS 3KkQORҥLWW
67
7
6ӕ FDUERQ
7rQ WK{QJ GөQJ
Yj Nê KLӋX 
FKӳ Yj FKӳ
7rQ KyD KӑF
Ύ ZĐſ ŶŚąŶ ŝŵŝĚĂnjŽůĞ
ϭϴ ϲ ,ŝƐƚŝĚŝŶĞ ;,ŝƐͿ;,Ϳ ĐŝĚɲͲĂŵŝŶŽɴ
ŝŵŝĚĂnjŽůĞƉƌŽƉŝŽŶŝĐ
Ύ ZĐſ ŶŚąŶ ŝŶĚŽů
ϭϵ ϭϭ dƌLJƉƚŽƉŚĂŶ;dƌƉͿ
t
ĐŝĚɲͲĂŵŝŶŽɴ ;ϯͲ
ŝŶĚŽůLJůͿƉƌŽƉŝŽŶŝĐ
ϮϬ ϱ WƌŽůŝŶ ;WƌŽͿ;WͿ ĐŝĚƉLJƌŽůŝĚŝŶ ϮͲ
ĐĂƌďŽdžLJůŝĐ
‡ 3UROLQ Oj PӝW DFLGLPLQHQKѭQJ YүQ ÿѭӧF [ӃS YjR DD FKXҭQ
9u Qy WKѭӡQJ JһS WURQJ WSFW SW SURWHLQQKѭ DD FzQ OҥL ϭϲ
'U'XRQJ7KL+RQJ'LHS
‡ 6HOHQRFVWHLQ
± Oj DD WKӭ 
± 7URQJ WSFW PӝW Vӕ SURWHLQ
HQ]PH;ĨŽƌ
ĞdžĂŵƉůĞ ŐůƵƚĂƚŚŝŽŶĞ
ƉĞƌŽdžŝĚĂƐĞƐ͕ƚĞƚƌĂŝŽĚŽƚŚLJƌŽŶŝŶĞ
ϱΖĚĞŝŽĚŝŶĂƐĞƐ͕ ƚŚŝŽƌĞĚŽdžŝŶ
ƌĞĚƵĐƚĂƐĞƐ͕ ĨŽƌŵĂƚĞ
ĚĞŚLJĚƌŽŐĞŶĂƐĞƐ͕ ŐůLJĐŝŶĞ
ƌĞĚƵĐƚĂƐĞƐ͕ ƐĞůĞŶŽƉŚŽƐƉŚĂƚĞ
ƐLJŶƚŚĞƚĂƐĞ Ϯ͕ŵĞƚŚŝŽŶŝŶĞͲZͲ
ƐƵůĨŽdžŝĚĞ ƌĞĚƵĐƚĂƐĞ ϭ;^WyϭͿ͕
ĂŶĚƐŽŵĞ ŚLJĚƌŽŐĞŶĂƐĞƐͿ͘
± /ĮDPLQ
± 7URQJ SW Fy FKӭD VHOHQ
± .K{QJ ÿѭӧF Pm KyD EӣL Eӝ
QXFOHRWLGHV
± 0m KyD EӣL 8*$8*$Oj
VWRSFRGRQ
± ĈѭӧF WKrP YjR WSFW SURWHLQ
WURQJ TXi WUuQK SKLrQ Pm
,,'DQKSKiS 3KkQORҥLWW
ϭϳ
'U'XRQJ7KL+RQJ'LHS
3KkQ ORҥL DD WKHR NKҧ QăQJ WәQJ KӧS FӫD Fѫ WKӇ$FLGDPLQ FҫQ
WKLӃW Yj NK{QJ FҫQ WKLӃW
ϭϴ
'U'XRQJ7KL+RQJ'LHS
7yP OҥL
DD Fѫ EҧQ
WURQJ WSFW SURWHLQ
'U'XRQJ7KL+RQJ'LHS ϭϵ
$D KLӃP JһSFiF GүQ [XҩW FӫD DD WKѭӡQJ JһS
ϱͲŚLJĚƌŽdžLJůLJƐŝŶĞ
*һS WURQJ WS ROODJHQ 7URQJ JOREXOLQFӫD WXӃQ JLiSG[FӫD WURVLQH
ϮϬ
'U'XRQJ7KL+RQJ'LHS
DҾƚƐҺĂĐŝĚĂŵŝŶŬŚĄĐ
Ϯϭ
'U'XRQJ7KL+RQJ'LHS
DҾƚƐҺĂĐŝĚĂŵŝŶŬŚƀŶŐĐſƚƌŽŶŐƉƌŽƚĞŝŶ
Ĉk Oj QKӳQJ
FKҩW TXDQ
WUӑQJ WURQJ
FKXӇQ KyD
PӝW YjL DD Oj
NVLQK
KRUPRQFKҩW
ÿLӅX KzD PLӉQ
GӏFK«
ϮϮ
'U'XRQJ7KL+RQJ'LHS
0ӝW Vӕ DD NK{QJ JһS WURQJ WSFW SURWHLQG[
FӫD FiF DD WKѭӡQJ JһS
‡ 9t Gө
± ȕDODQLQ
± $FLGJDPLQREXWULF *$%$
;EĞƵƌŽƚƌĂŶƐŵŝƚƚĞƌͿ
Ϯϯ
'U'XRQJ7KL+RQJ'LHS
$FLGDPLQFyWtQKÿӝF
N̽m Trogia venenata
ŚŽƵ͕͘zĞƚĂů͘;ϮϬϭϮͿ͘ΗǀŝĚĞŶĐĞĨŽƌƚŚĞEĂƚƵƌĂůdŽdžŝŶƐĨƌŽŵƚŚĞ
DƵƐŚƌŽŽŵ dƌŽŐŝĂǀĞŶĞŶĂƚĂ ĂƐĂĂƵƐĞŽĨ^ƵĚĚĞŶhŶĞdžƉĞĐƚĞĚ
ĞĂƚŚŝŶzƵŶŶĂŶWƌŽǀŝŶĐĞ͕ŚŝŶĂΗ͘ ŶŐĞǁĂŶĚƚĞŚĞŵŝĞ
/ŶƚĞƌŶĂƚŝŽŶĂůĚŝƚŝŽŶ ϱϭ ;ϭϬͿ͗ϮϯϲϴʹϮϯϳϬ Ϯϰ
'U'XRQJ7KL+RQJ'LHS
‡ iF DD WKѭӡQJ JһS WURQJ SWSURWHLQKҫX KӃW Oj /DD
‡ 'DD FKӍ JһS ӣWKjQK 7%FӫD PӝW Vӕ YLNKXҭQ
± 9''JOXWDPLF WuP WKҩ ӣYӓ B. subtilis
‡ iF DD 7+EҵQJ SS++WKѭӡQJ ӣGҥQJ ÿӗQJ SKkQFӫD 'Yj
/o Yj ÿF Nê KLӋX Oj '/DD
‡ .êKLӋX'Yj/ELӇXWKӏGҥQJFҩXWU~FNK{QJFKӍFKLӅXTXD
FӫDÈ6SKkQFӵF
‡ 'ҥQJ'Yj/FӫDFQJDDFyJyFTXDÿһFKLӋXEҵQJQKDX
QKѭQJWUiLGҩX
± 9''
DODQLQFyĮ'
  
± 9'/
DODQLQFyĮ'
 
‡ 6ӕÿӗQJ SKkQ OұS WKӇ Q Q Vӕ FDUERQEҩW ÿӕL
‡ ĈD Vӕ DD WKѭӡQJ JһS FKӍ Fy 
o Ĉ3OұS WKӇ
‡ 7KUHRQLQ Yj LVROHXFLQ Fy 
o Ĉ3OұS WKӇ
,+yD KӑF OұS WKӇ FӫD ĮDPLQRDFLGWW
dŚƌĞŽŶŝŶ Ϯϱ
'U'XRQJ7KL+RQJ'LHS
,+yD KӑF OұS WKӇ FӫD ĮDPLQRDFLGWW
(QDQWLRPHU ÿӗQJ SKkQ ÿӕL KuQK
ĈӗQJ SKkQ OұS WKӇ 'KD/
Ϯϲ
'U'XRQJ7KL+RQJ'LHS
,,7tQKFKҩWFӫDDFLGDPLQ
,,7tQKFKҩWYұWOê
,,7tQKFKҩWOѭӥQJWtQK
,,7tQKFKҩWKyDKӑF
ƌ͘ƵŽŶŐdŚŝ,ŽŶŐŝĞƉ Ϯϳ
,,7tQK FKҩWYұWOêFӫD DD
,,7tQK KzD WDQ
± 'Ӊ WDQWURQJ QѭӟF22+ Yj 1+

± Ĉӝ WDQWURQJ QѭӟF SKө WKXӝF 5
‡ *OFLQ UҩW GӉ WDQ5 +
‡ /HXFLQ Yj LVROHXFLQ 5
tW WDQ
‡ 5Fy QKyP ±2+22+1+ WDQGӉ KѫQ
± iF DD tW WDQWURQJ DOFROHWKHUGP
KӳX Fѫ
QJRҥL WUӯ SUROLQ Yj
KGUR[SUROLQ
± iF DD WDQWURQJ DFLGNLӅP ORmQJ WҥR
WKjQK FiF PXӕL FӫD DDQJRҥL WUӯ
WURVLQ WDQtW
'ůLJĐŝŶ
ŝƐŽůĞƵĐŝŶ
Ϯϴ
'U'XRQJ7KL+RQJ'LHS
,,9ӏ
 iF DD Fy Yӏ QJӑW
 /HXFLQ NK{QJ Yӏ
 ,VROHXFLQ Yj DUJLQLQ Fy Yӏ ÿҳQJ
 0XӕL QDWUL FӫD DFLGJOXWDPLF Fy Yӏ QJӑW NLӇX
ÿҥP
,,7tQK FKҩW YұWOêFӫD DD
,,7tQK TXDQJ KRҥW FӫD DD
± +ҫX KӃW DD Fy WtQK TXDQJ KRҥWNKҧ QăQJ TXDPһW SKҷQJ iV
SKkQ FӵF
± 7Uӯ JOFLQ
Ϯϵ
'U'XRQJ7KL+RQJ'LHS
,,3Kә KҩS WKX
± iF DD NK{QJ KҩS WKX$6ӣEѭӟF VyQJ
9LVKRһF 89Fy O ! QPQJRҥL WUӯ DD
YzQJ
± 7URVLQWUSWRSKDQSKHQODODQLQ KҩS WKX
PҥQK ӣYQJ 89QP
± VWHLQ KҩS WKX ӃX ӣO QP
± iF DD NKiF KҩS WKX ӣO QP
± 7URVLQ Fy WURQJ WSFW FӫD KҫX KӃW SURWHLQ
o ÿӏQK OѭӧQJ SURWHLQӣO QP
3Kә KҩS WKX 89FӫD 7USWRSKDQ
WURVLQSKHQODODQLQ
,7tQK FKҩW Oê KӑF FӫD DD
ϯϬ
'U'XRQJ7KL+RQJ'LHS
3KәKҩSWKX89FӫD7USWRSKDQWURVLQSKHQODODQLQ
ϯϭ
'U'XRQJ7KL+RQJ'LHS
,,7tQK OѭӥQJ WtQK FӫD DD
‡ 7 WKHR S+P{L WUѭӡQJ DD
WKӇ KLӋQ WtQK DFLGKDWtQK
EDVH
± 7URQJ PWUNLӅPDD SKkQ O
QKѭ PӝW DFLGSKyQJ WKtFK
+deprotonated
± 7URQJ PWUDFLGKÿQKѭ PӝW
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  • 25. ^dd ^Һ dġŶ ƚŚƀŶŐ ĚӅŶŐ ǀă Ŭlj ŚŝҵƵ ;ϯĐŚӋ ǀă ϭĐŚӋͿ dġŶ ŚſĂ ŚҸĐ ϭϰ ϲ LJƐŝŶ ;LJƐͿ;Ϳ ĐŝĚɲ͕ɸͲĚŝĂŵŝŶŽ ŶͲ ĐĂƉƌŽŝĐ ϭϱ ϲ ƌŐŝŶŝŶ ;ƌŐͿ;ZͿ ĐŝĚɲͲĂŵŝŶŽɷͲ ŐƵĂŶŝĚŽͲŶǀĂůĞƌŝĐ //͘Ϯ͘Ϯ͘ ĐŝĚĂŵŝŶ ŵҢĐŚ ǀžŶŐ ĐŝĚ ĂŵŝŶ Đſ ŶŚąŶ ƚŚҿŵ ϭϲ ϵ WŚĞŶLJůĂůĂŶŝŶ ;WŚĞͿ ;Ϳ ĐŝĚɲͲĂŵŝŶŽɴͲ ƉŚĞŶLJůƉƌŽƉŝŽŶŝĐ ϭϳ ϵ dLJƌŽƐŝŶ ;dLJƌͿ;zͿ ĐŝĚɲͲĂŵŝŶŽɴͲ;ʌͲ ŚLJĚƌŽdžLJƉŚĞŶLJůͿ ƉƌŽƉŝŽŶŝĐ ,,$FLGDPLQ NLӅPDFLGGLDPLQ PRQRFDUER[OLF
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  • 34. ;EĞƵƌŽƚƌĂŶƐŵŝƚƚĞƌͿ Ϯϯ 'U'XRQJ7KL+RQJ'LHS $FLGDPLQFyWtQKÿӝF N̽m Trogia venenata ŚŽƵ͕͘zĞƚĂů͘;ϮϬϭϮͿ͘ΗǀŝĚĞŶĐĞĨŽƌƚŚĞEĂƚƵƌĂůdŽdžŝŶƐĨƌŽŵƚŚĞ DƵƐŚƌŽŽŵ dƌŽŐŝĂǀĞŶĞŶĂƚĂ ĂƐĂĂƵƐĞŽĨ^ƵĚĚĞŶhŶĞdžƉĞĐƚĞĚ ĞĂƚŚŝŶzƵŶŶĂŶWƌŽǀŝŶĐĞ͕ŚŝŶĂΗ͘ ŶŐĞǁĂŶĚƚĞŚĞŵŝĞ /ŶƚĞƌŶĂƚŝŽŶĂůĚŝƚŝŽŶ ϱϭ ;ϭϬͿ͗ϮϯϲϴʹϮϯϳϬ Ϯϰ 'U'XRQJ7KL+RQJ'LHS
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  • 161. ĈҥL FѭѫQJ9Ñ1*/8Æ1+8ӆ13527(,1 3URWHLQ WӃ EjR OX{Q ÿѭӧF ÿәL PӟL 4Xi WUuQK WKRiL KRi SURWHLQ WӃ EjR QKӡ HQ]P FDWHSVLQ $ % « WURQJ OVRVRP FӫD WӃ EjR 3URWHLQ VDX NKL ăQ Yj WLrX KyD o FXQJ FҩS DD FKR Fѫ WKӇ DD Qj GQJ ÿӇ 7+ SURWHLQ FKR Fѫ WKӇ FiF SURWHLQ FӫD FiF Wә FKӭF Fѫ WKӇ NK{QJ QJӯQJ WKRiL KyD o Fy Vӵ FKXӇQ KyD OLrQ WөF FӫD 1 KϮ н ,ϮK ϰϬϬŐͬŶŐăLJ WƌŽƚĞŝŶ ƚұ ď㎠ĐŝĚ ĂŵŝŶ ϯͬϰ ϭͬϰ dŚŽĄŝ ŚſĂ dҼŶŐ ŚӄƉ 'U'XRQJ7KL+RQJ'LHS ϵϳ 'ӵ WUӳ SURWHLQOӓQJ OҿR ‡ ӣQJѭӡL WUѭӣQJ WKjQK Vӵ TXDYzQJ FӫD SURWHLQOj KJK
  • 162. ‡ OѭӧQJ SURWHLQGӵ WUӳ OӓQJ OҿR Oj NJo PiX JDQFѫ ‡ SURWHLQFӕ ÿӏQKWLPQmR ‡ Fѫ o FXQJ FҩS SURWHLQFKR QmRWLP NKL FҫQ ‡ SURWHLQFӫD JDQ+7J o WKD ÿәL WKHR FKӃ ÿӝ ăQ 6ӵ FkQ EҵQJ QLWR QJѭӡL %7ăQ XӕQJ ÿҫ ÿӫ ÿҥP 1[XҩW 1QKұS TXDQѭӟF WLӇX
  • 163. ‡ .KL ÿyL KRһF VX ӃX o Fy Vӵ FkQ EҵQJ 1 kP 1QKұS 1[XҩW ‡.KL SKiW WULӇQ KDÿDQJ EuQK SKXF o Fy Vӵ FkQ EҵQJ GѭѫQJ 1QKұS !1[XҩW ĈҤ,ѬѪ1*FkQ EҵQJ ÿӝQJ FӫD SURWHLQ 'U'XRQJ7KL+RQJ'LHS ϵϴ ,ĈҥL FѭѫQJ6ѪĈӖ+7Ә1*48È7 WƌŽƚĞŝŶ ŶŐŽҢŝ ƐŝŶŚ ;dͿ WƌŽƚĞŝŶ ŶҾŝ ƐŝŶŚ ;ĐĄĐ ĐƋͿ WŽůLJĂŵŝŶ EĞƵƌŽƚƌĂŶƐŵŝƚƚĞƌ ,Ğŵ͕WƵƌŝŶ͕ WLJƌŝŵŝĚŝŶ E,ϯ hZ ŝƉŝĚ 'ůƵĐŝĚ KϮ н,ϮK /D/E 'U'XRQJ7KL+RQJ'LHS ϵϵ ,ĈҥL FѭѫQJ QJXӗQ JӕF DD Fѫ WKӇ 'U'XRQJ7KL+RQJ'LHS ϭϬϬ
  • 164. ĈҥL FѭѫQJ6ѫ ÿӗ +3URWLG 3HSWLGWLrXKyD 3URWHLQKҩSWKX 2+28Ur4 6ҧQSKҭPVLQKKӑF ÿһFELӋW ӔQJWLrXKyD 7ӃEjR $FLGDPLQ 3URWHLQ 'U'XRQJ7KL+RQJ'LHS ϭϬϭ 7LrXKyD ‡ 3URWHLQWKӭFăQÿѭӧFFiFHQ]PHWKӫ SKkQSURWHLQproteinase
  • 165. WURQJGӏFKWLrX KyDWKӫSKkQWKjQKFiFSHSWLGFXӕLFQJ WKjQKFiFDDWӵGR ‡ Proteinase OjFiFpeptidase [~FWiFSKҧQ ӭQJFҳWÿӭWFiFOLrQNӃWSHSWLGYӟLVӵ WKDPJLDFӫDQѭӟF 'U'XRQJ7KL+RQJ'LHS ϭϬϮ 7LrXKyD 7ҥL ӕQJ WLrX KyD SURWHLQDVHSHSWLGDVH GӏFK WLrX KyDGӏFK YӏGӏFK Wө GӏFK WUjQJ 0ӛL SHSWLGDVHFy WGÿһF KLӋX ÿӕL YӟL Yӏ WUt ONSHSWLG YӟL EҧQ FKҩW FӫD 5 GӏFK WLrX KyDSHSWLGDVHNK{QJ KRҥW ÿӝQJ SURHQ]PH
  • 166. o o SHSVLQRJHQ ӕQJ WLrX KyDSHSWLGDVHKRҥW ÿӝQJ SHSVLQ
  • 167. 'U'XRQJ7KL+RQJ'LHS ϭϬϯ 7LrX KyD3KkQ ORҥL SHSWLGDVH ‡ (QGRSHSWLGDVH ± [WWKӫ SKkQ ON SHSWLG ErQ WURQJ FKXӛL SROSHSWLGH ± 9GӣӕQJ WLrX KyD ‡ 3HSVLQ ‡ 7USVLQ ‡ KPRWUSVLQ ‡ ([RSHSWLGDVH ‡ [WWKӫ SKkQ ONSHSWLG ӣÿҫX FӫD FKXӛL SROSHSWLGH ‡ 9G ‡ DUER[SHSWLGDVH ‡ $PLQRSHSWLGDVH ‡ 'LSHSWLGDVH 'U'XRQJ7KL+RQJ'LHS ϭϬϰ
  • 168. 'LSHSWLGDVH ‡ y WURQJ GӏFK UXӝW ‡ 7Kӫ SKkQ FiF GLSHSWLGH o DD Wӵ GR DWHSVLQHQ]P WKӫ SKkQ SURWHLQ FӫD FiF Wә FKӭF ‡ KLD ORҥL$% ‡ WGWѭѫQJ ÿѭѫQJSHSVLQWUSVLQ FKPRWUSVLQ iF 7%FNJQJ Fy FDUER[SHSWLGDVH Yj DPLQRSHSWLGDVH ‡ DWHSVLQFy WURQJ OVRVRPH o Jk KLӋQ WѭӧQJ Wӵ WLrX FӫD 7% ‡ ѬӟS [iFGQJ IRUPRO OjP ELӃQ WtQK SURWHLQWURQJ ÿy Fy Fҧ FDWHSVLQ
  • 169. o JLӳ [iF QJXrQ YҽQ ĚŝƉĞƉƚŝĚĂƐĞ 'U'XRQJ7KL+RQJ'LHS ϭϬϱ +ҩSWKө ‡ 4XDTXi WUuQK WLrX KyD WUrQFiF DD Wӵ GRÿѭӧF SKyQJ WKtFK UӗL ÿѭӧF KҩS WKө TXDQLrP PҥF UXӝW QRQYjR WƭQK PҥFK FӱD WӟL JDQ Yj TXDPiX WӟL FiF WE Yj P{ ‡ 7ҥL WEFiF DFLGDPLQ VӁ ÿѭӧF ± WKRiL KyDWҥR XUr2+2FXQJ FҩS QăQJ OѭӧQJ ‡ 'QJ ÿӇ WҥR FiF SWVLQK KӑF TXDQ WUӑQJ HQ]PH KRUPRQH«
  • 170. ‡ 6LQK WәQJ KӧS SURWHLQ ‡ 6ҧQ SKҭP ÿjR WKҧL Oj FiF KӧS FKҩW FKӭD QLWѫFKӫ ӃX Oj XUr 'U'XRQJ7KL+RQJ'LHS ϭϬϲ 6ѫÿӗ+3URWLG 3HSWLGWLrXKyD 3URWHLQKҩSWKX 2+28Ur4 6ҧQSKҭPVLQKKӑF ÿһFELӋW ӔQJWLrXKyD 7ӃEjR $FLGDPLQ 3URWHLQ 'U'XRQJ7KL+RQJ'LHS ϭϬϳ +ҩS WKX 4Xi WUuQK KҩS WKX NK{QJ SKҧL Oj NKXӃFK WiQ ÿѫQ WKXҫQ FiF /DD o YFWtFK FӵF TXD WKjQK UXӝW YjR PiX o FҫQ $73Yj SULGR[DO SKRVSKDWH FiF 'DD o NKXӃFK WiQ Wӵ GR TXDWKjQK UXӝW o FiF DD KҩS WKX PӝW FiFK FҥQK WUDQK o PӝW DD ăQ YjR TXi WKӯD o FҥQK WUDQK Vӵ KҩS WKX FӫD DD NKiF 'U'XRQJ7KL+RQJ'LHS ϭϬϴ
  • 171. 7KRiL KyD DFLGDPLQ 'U'XRQJ7KL+RQJ'LHS ϭϬϵ 1KӳQJ SKҧQ ӭQJ WKRiL KyD FKXQJ 'U'XRQJ7KL+RQJ'LHS ϭϭϬ È48È75Î1+7+2È,+Ï$+81* ‡ .Kӱ FDUER[O 2 5²+²22+ 5²+²1+ Decarboxylase SULGR[DO SKRVSKDW
  • 173. 1+ .KӱDPLQ Kh΅ amin oxy hóa Oj PӝW TXi WUuQK TXDQ WUӑQJ WURQJ ÿy QKyP 1+ ÿѭӧF WiFK NKӓL SKkQ Wӱ DD GѭӟL GҥQJ 1+ 'U'XRQJ7KL+RQJ'LHS ϭϭϭ Ϯ͘ϭ͘Śӊ ĐĂƌďŽdžLJůʹ ƚŚŽĄŝ ŚſĂ ɲͲKK, ĐӆĂ ĂĐŝĚĂŵŝŶ 'U'XRQJ7KL+RQJ'LHS ϭϭϮ
  • 174. 7+2È,+Ï$D D22+Ӫ$È$$ ƒ /j SKɠQ ͩQJ NKͭ FDUER[OFͧD $$WɞR DPLQ WɉɇQJ ͩQJ ƒ 7Kɉ͝QJ Oj FiF DPLQ Fy KRɞW WtQK VLQK K͍F ƒ 3KͩF KͣS HQ]P GHFDUER[ODVH Yj FRHQ]P YLWDPLQ% ƒ 9G GHFDUER[ODVH ;ƉLJƌŝĚŽdžĂů ƉŚŽƐƉŚĂƚĞͿ y WGJLmQ PҥFK FRWKҳW SKӃ TXҧQ WăQJ WtQK WKҩP WKjQK PҥFK« 'U'XRQJ7KL+RQJ'LHS ϭϭϯ 3ULGR[DO SKRVSKDWH3/3
  • 175. YLW % 'U'XRQJ7KL+RQJ'LHS ϭϭϰ ѫ FKӃ SKҧQ ӭQJ NKӱ 2 FӫD DD 'U'XRQJ7KL+RQJ'LHS ϭϭϱ 7KRiL KyD FDUER[O 0ӝW YjL Yt Gө 'U'XRQJ7KL+RQJ'LHS ϭϭϲ
  • 176. .Kӱ DPLQ ± WKRiL KyD 1,7Ѫ FӫD DFLGDPLQ 'U'XRQJ7KL+RQJ'LHS ϭϭϳ .KӱDPLQ R[KyD ++2 ‡ 5²+²22+ 5222+1+ Deaminase ɲͲFHWR DFLG 1+ .Kӱ DPLQ R[KyD JӗP Jÿ JLDL ÿRҥQ NKӱ hydro EӣL dehydrogenase + 5²+²22+ 5²²22+ 'HKGURJHQDVH 1+ 1+ D D ,PLQR DFLG )$' )$'+ 'U'XRQJ7KL+RQJ'LHS ϭϭϴ .KӱDPLQ R[KyD WW
  • 177. ‡ JLDL ÿRҥQ WKӫ SKkQ Wӵ SKiW ‡ 5²²22++2 5² ² 22+1+ ‡ 1+ 2 ‡ D ,PLQR DFLG D D FHWR DFLG 1KLӅX DD NKy Eӏ NKӱ DPLQWUӯ glutamate GӉ Eӏ NKӱ WUӵF WLӃS Yu glutamate dehydrogenase (coenzym: NAD ho͏c NADP) KRҥW ÿӝQJ PҥQK ӣS+S+Fѫ WKӇ
  • 178. FiF DD NKiF VӁ ÿѭӧF NKӱ JLiQ WLӃS QKӡ SKӕL KӧS Sѭ FKXӇQ ± NKӱ DPLQ Kh΅ amin oxy hóa trΉc ti͗p L- glutamate: 'U'XRQJ7KL+RQJ'LHS ϭϭϵ .Kӱ DPLQ R[KyD JOXWDPDW JOXWDPDW GHKGURJHQDVH
  • 180. Ĉk Oj Sѭ WKXұQ QJKӏFKKLӅX QJѭӧF OҥL o DPLQ KyDNKӱ R[KDKGURKyD
  • 181. o /j Fѫ FKӃ JҳQ 1+ YjR PӝW KFKӳX Fѫ o JҳQ 1+ YjR Į NHWRJOXWDULF o Vӵ FKXӇQ QKyP 1+ 6ӵ FKXӇQ Wӯ JOXWDPDWH VDQJĮNHWRJOXWDULF 63 FKX WUuQK DFLGFLWULF
  • 183. *OXWDPDW GHKGURJHQDVH ‡ ӢĈ9EұF FDR ± *OXWDPDWH GHKGURJHQDVH FRHQ]PHOj 1$'
  • 184. [WSѭ NKӱ DPLQ R[ KyD o WKRiL KyD DD ± 7URQJ W WKӇ 7%JDQ
  • 185. 1+ JLҧL SKyQJ VӁ ÿL YjR FWUuQK XUH ‡ ӣYLVLQK YұW ± /JOXWDPDWH GHKGURJHQDVH YӟL FRHQ]PHNKӱ 1$'3+
  • 186. [WSѭ DPLQ KyD NKӱ R[o 67+ DD ± o ӣYLVLQK YұWNKҧ QăQJ 7+DD ! WKRiL KyD 'U'XRQJ7KL+RQJ'LHS ϭϮϭ .Kӱ DPLQ R[KyD WW
  • 187. - Kh΅ gián ti͗p các aa khácSѭ FKXӇQ Yj NKӱ DPLQ D HWRJOXWDUDW D FHWRDFLG
  • 188. 3ѭ FKXӇQ DPLQ 3ѭ NKӱ DPLQ iF DD NKiFFy HQ]PHKRҥW ÿӝQJ ӣS+ o o TXi NLӅP y FRHQ]PH )01KD)$'
  • 189. o KÿӃX o .Kӱ DPLQ JLiQ WLӃS TXDSѭ FKXӇQ DPLQ 'U'XRQJ7KL+RQJ'LHS ϭϮϮ .Kӱ DPLQ R[KyD ± SѭFKXӇQ QKyP DPLQ ± 1Kӡ KӋ WKӕQJ FKXӇQ ± NKӱ DPLQ FiF DFLG DPLQ ÿӅX ÿѭӧF NKӱ DPLQ WҥR DFHWR DFLGYj VSÿjR WKҧL Oj 1+
  • 190. ± D D–cetoglutarat Oj FKҩW WUXQJ JLDQ KRҥW ÿӝQJ QKѭ PӝW ³FRQWKRL´YұQ FKXӇQ QKyP DPLQ 7UDQVDPLQDWLRQUHDFWLRQV ;D ŵŝŶŽĂĐŝĚͿ ;DͲĐĞƚŽĂĐŝĚͿ 'U'XRQJ7KL+RQJ'LHS ϭϮϯ iF Sѭ NKӱ DPLQ NKiF .Kӱ DPLQWҥR 1+ Yj DFLGWѭѫQJ ӭQJ 5+1+
  • 191. 22++ o 5+22+1+ .Kӱ DPLQ QӝL SKkQ WӱWҥR 1+ Yj DFLGNK{QJ QR 5++1+
  • 192. 22++ o 5+ +22+1+ .Kӱ DPLQ WKӫ SKkQWҥR 1+ Yj R[DFLG 5+1+
  • 195. KXӇQDPLQ ‡ 3KҧQ ӭQJ FKXӇQ DPLQ ÿѭӧF [~F WiF EӣL HQ]PH transaminase Fy FRHQ]PHOj pyridoxal phosphate (vitamin B6) ‡ (Q]P WUDQVDPLQDVH Fy QKLӅX ӣJDQWLPJӗP ORҥL ± *27 JOXWDPDWH R[DORDFHWDW WUDQVDPLQDVH
  • 201. D HWRJOXWDUDW *27 'U'XRQJ7KL+RQJ'LHS ϭϮϲ *37 JOXWDPDWHSUXYDW WUDQVDPLQDVH
  • 203. D HWRJOXWDUDW *37 'U'XRQJ7KL+RQJ'LHS ϭϮϳ Ѫ+ӂ3+Ҧ1Ӭ1*+8ӆ1$0,1 9GSѭ FKXӇQ DPLQ Wӯ DFLGJOXWDPLF o DFLGSUXYLF *37[~F WiF
  • 204. [ҧ UD TXD*Ĉ $JOXWDPLF 3ULGR[DO SKRVSKDWHFRHQ]PH
  • 205. o o $NHWRJOXWDULF 3ULGR[DPLQ 3KRVSKDWH 3ULGR[DPLQ 3KRVSKDWH$3UXYLF o 3ULGR[DO SKRVSKDWH$ODQLQ 'U'XRQJ7KL+RQJ'LHS ϭϮϴ
  • 206. *27*37 ӬQJ GөQJ OkP VjQJ ™ ;iF ÿӏQK KRҥW ÿӝ WUDQVDPLQDVH 6*27$67
  • 209. WURQJ FiF EӋQK Oê WLPJDQ KDFѫ YkQ« ™ *27Yj *37Oj FiF HQ]P QӝL EjREuQK WKѭӡQJ WURQJ KXӃW WKDQK 8,O 'Kd ㎠ƚӇҿŶŐ dLJƚŚҳ 'Wd ăŽƚӇҿŶŐ ™ 1KӗL PiX Fѫ WLPFKӫ ӃX WăQJ *27FKӍ Vӕ *27*37! ™ 9LrP JDQ VLrX YLWăQJ Fҧ *37Yj *27*37WăQJ QKLӅX *27*37 'U'XRQJ7KL+RQJ'LHS ϭϮϵ +8ӆ1+Ï$1+ ‡ 1+ ÿѭӧF WҥR WKjQK ӣFiF P{FKӫ ӃX GRVӵ NKӱ DPLQ R[KyD FiF DFLGDPLQ ‡ 1+ Oj FKҩW ÿӝF ÿӕL YӟL Fѫ WKӇ oQy ÿѭӧF Fѫ WKӇ NKӱ ÿӝF EҵQJ FiFK NӃW KӧS YӟL acid glutamic WҥR WKjQK glutamine NK{QJ ÿӝF oQKӡ HQ]PHglutamine synthetase. EҾŝ ƐŝŶŚ 1JRҥL VLQK ‡.Kӱ DPLQ R[KyD FӫD FiF DFLGDPLQ ‡7KRiL KyD EDVH3XULQSULPLGLQ 9LNKXҭQ Fy HQ]P WKӫ SKkQ SURWHLQWURQJ UXӝW 1+70FӱD !1+WXҫQ KRjQ OҫQ
  • 210. E,ϯ 'U'XRQJ7KL+RQJ'LHS ϭϯϬ 6ӵ WҥR WKjQK JOXWDPLQH ‡ *OXWDPLQÿѭӧFYFWURQJPiXÿӃQJDQJLҧLSKyQJ1+ ‡ VDXÿy1+ ÿѭӧFWәQJKӧSWKjQKXUrFKXWUuQKXUr
  • 212. glutamine synthetase. JOXWDPLQH+2 JOXWDPDWH1+ 'U'XRQJ7KL+RQJ'LHS ϭϯϭ 'h 'h 'hdD/E ;ϲϬͲϭϬϬŵŐͬůͿ EӇӀĐ ƚŝҳƵ 1+ PJO1+
  • 213. DN 1+ Dh 'E d,ѺE E,ϯ E,ϯ hZ DhҌ/DKE 9ұQ FKXӇQ 1+ WURQJ Fѫ WKӇ 'U'XRQJ7KL+RQJ'LHS ϭϯϮ
  • 214. 7ҥL JDQ Yj WKұQ ™7ҥL JDQ1+ YjR FKX WUuQK XUr ™7ҥL WKұQWKXӹ SKkQ JOXWDPLQHFKR 1+ WҥR PXӕL DPRQ Yj ÿjR WKҧL WKHR QѭӟF WLӇXJL~S WKҧL +JL~S WKăQJ EҵQJ DFLGEDVH 7KXӹ SKkQ JOXWDPLQHWKұQ WăQJ WURQJ WRDQ PiX 7KXӹ SKkQ JOXWDPLQHWKұQ JLҧP WURQJ NLӅP PiX 'U'XRQJ7KL+RQJ'LHS ϭϯϯ 7+JOXWDPDWHWӯJOXWDPLQH 'U'XRQJ7KL+RQJ'LHS ϭϯϰ $/$1,19Ұ1+8ӆ11+ + 2+ 2 2 *OXWDPDWH DNHWRJOXWDUDWH + + 2+ 1+ 2 3UXYDWH $ODQLQH *OXWDPDWHDPLQRWUDQVIHUDVH % $ODQLQYұQFKXӇQ1+ ӣP{FyFѭӡQJÿӝKRҥWÿӝQJPҥQKOj FѫYӅJDQFKXWUuQK*OXFRVH$ODQLQ
  • 215. ALANIN vͅn chuy͛n NH4 + và khung carbon (pyruvat) v͙ gan ÿ͛ tái t̹o glucose, glucose l̹i ÿ́ͻc vͅn chuy͛n ÿ͗n s΅ dͽng ͷ c˿, quá trình này mang tính ch̽t có lͻi cho c˿ th͛ sͩng (ti͗t ki͟m năng ĺͻng) 'U'XRQJ7KL+RQJ'LHS ϭϯϱ 7Ә1*+Ӧ3*/87$0,17Ҥ,1­2 /j Fѫ FKӃ NKӱ ÿӝF 1+ FKӫ ӃX FӫD QmR 1KѭQJ QӃX 1+ PiX FDR Æ «ÆNLӋW TXӋ FiF FKҩW WUXQJ JLDQ WURQJ FKX WUuQK DFLGFLWULF Glutamate dehydrogenase 1$'+1$' D D.HWRJOXWDUDWH 1+ *OXWDPDWH Glutamine synthetase *OXWDPLQH 1+ $73 $'33L 'U'XRQJ7KL+RQJ'LHS ϭϯϲ
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