FÍGADO Repouso Exerc. RepousoExerc. MÚSCULO AlimentadoJejum.
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Transcript of FÍGADO Repouso Exerc. RepousoExerc. MÚSCULO AlimentadoJejum.
FÍGADO
FÍGADO
Repouso Exerc.Repouso Exerc.
MÚSCULO
Alimentado Jejum
G3P
pyruvate
glicose
citrate
fatty acyl -CoA
fatty acid
HEPATOCYTE
F1,6BP
G3P DHAP
acetyl-CoA
malonyl-CoA
TAG
pyruvate
acetyl-CoACO2
CO2
citrate
pyruvate
acetyl-CoACO2
CO2
citrate
HEPATOCYTE
glicose
GLICÓLISE
Síntese de Ácidos graxos
VLDL
b – Ox.C. Krebs FosFoxCat. aa
Gliconeog.
??
pyruvate
pyruvate
GLYCOLYSIS
glucose
oxaloacetate
malate
fumaratesuccinyl-CoA
succinate
α-ketoglutarate
citrate
isocitrate
acetyl-CoA
ISOCITRATEDEHYDROGENASE
-KETOGLUTARATEDEHYDROGENASE
SUCCINATEDEHYDROGENASE
NADH
NAD+
NADH
NADH
FADH2FAD
ATP
ADP+ Pi
NAD+
NAD+
CO2
CO2
citrate
acetyl-CoA
malate
oxaloacetate
palmitate
ACC
FASmalonyl-CoA
CITRATE LYASE
MALATEDEHYDROGENASE
MALIC ENZYME
pyruvate
NAD+
NADH
NADP+
NADPH
MALATEDEHYDROGENASE
H+
H+
H+
H+
H+
H+
e-
e-e-
e-
Otto Meyerhof (Prêmio Nobel de Medicina em 1922)
iodoacetamida
ATP
ADP
ATP
ADP
glicose-6-fosfato
glicose
frutose-6-fosfato
frutose-1,6-bisfosfato
gliceraldeído-3-fosfato
piruvato
hexocinase
fosfo-hexose isomerase
fosfofrutoocinase
aldolase
piruvato
acetil-CoA
CO2
CO2
Mesmo com iodoacetamida em concentrações que inibem completamente a aldolase, havia desprendimento de CO2 em células incubadas com glicose
Compostos iniciais da glicólise podem ser oxidados em outra via
Fritz Lipmann(Prêmio Nobel de Medicina em 1953)Efraim Racker
A liberação de CO2 estava associada à redução de NADP+ e à formação de pentoses
Compostos iniciais da glicólise são oxidados e descarboxilados com concomitante redução de NADP+ a NADPH
6C 5C
CO2
NADP+ NADPH
G6P
glicose
F6P
F1.6BP
G3P
piruvato
piruvato
acetil-CoA
CO2
CO2
DHAP
ribulose-5-PCO2
NADP+ NADPH
glucose-6P 6P-glucolnolactone 6P-gluconate
GLUCOSE-6P DEHYDROGENASE
LACTONASE 6P-GLUCONATE DEHYDROGENASE
NADPHNADP+ NADPHNADP+
CO2
ribulose-5P
fructose-6P
erythrose-4P
glyceraldehyde-3P
glyceraldehyde-3P
ribose-5P xylulose-5P
sedoheptule-7P
ribulose-5P
TRANSKETOLASE
TRANSALDOLASETRANSKETOLASE
RIBULOSE-5P EPIMERASE
RIBULOSE-5P ISOMERASE
glucose-6P 6P-glucolnolactone 6P-gluconate
GLUCOSE-6P DEHYDROGENASE
LACTONASE 6P-GLUCONATE DEHYDROGENASE
NADPHNADP+ NADPHNADP+CO2
fructose-6P
erythrose-4P
glyceraldehyde-3P
glyceraldehyde-3P
ribose-5P xylulose-5P
sedoheptule-7P
ribulose-5P
TRANSKETOLASE
TRANSALDOLASETRANSKETOLASE
RIBULOSE-5P EPIMERASE
RIBULOSE-5P ISOMERASE
3 glucose-6P + 6 NADP+ + 3 H2O3 ribulose-5P + 3 CO2 + 6 NADPH + 6 H+
2 fructose-6P + 1 glyceraldehyde-3P
OXIDATIVE PHASE
NON-OXIDATIVE PHASE
OVERALL EQUATION
glucose-6P 6P-glucolnolactone 6P-gluconate
GLUCOSE-6P DEHYDROGENASE
LACTONASE 6P-GLUCONATE DEHYDROGENASE
NADPHNADP+ NADPHNADP+CO2
fructose-6P
erythrose-4P
glyceraldehyde-3P
glyceraldehyde-3P
ribose-5P xylulose-5P
sedoheptule-7P
ribulose-5P
TRANSKETOLASE
TRANSALDOLASETRANSKETOLASE
RIBULOSE-5P EPIMERASE
RIBULOSE-5P ISOMERASEglucose-6P 6P-glucolnolactone 6P-gluconate
GLUCOSE-6P DEHYDROGENASE
LACTONASE 6P-GLUCONATE DEHYDROGENASE
glucose-6P 6P-glucolnolactone 6P-gluconate
GLUCOSE-6P DEHYDROGENASE
LACTONASE 6P-GLUCONATE DEHYDROGENASE
NADPHNADP+ NADPHNADP+ NADPHNADP+ NADPHNADP+CO2CO2
fructose-6P
erythrose-4P
glyceraldehyde-3P
glyceraldehyde-3P
ribose-5P xylulose-5P
sedoheptule-7P
ribulose-5P
TRANSKETOLASE
TRANSALDOLASETRANSKETOLASE
RIBULOSE-5P EPIMERASE
RIBULOSE-5P ISOMERASE
fructose-6P
erythrose-4P
glyceraldehyde-3P
glyceraldehyde-3P
ribose-5P xylulose-5P
sedoheptule-7P
ribulose-5P
TRANSKETOLASE
TRANSALDOLASETRANSKETOLASE
RIBULOSE-5P EPIMERASE
RIBULOSE-5P ISOMERASE
3 glucose-6P + 6 NADP+ + 3 H2O3 ribulose-5P + 3 CO2 + 6 NADPH + 6 H+
2 fructose-6P + 1 glyceraldehyde-3P
3 glucose-6P + 6 NADP+ + 3 H2O3 ribulose-5P + 3 CO2 + 6 NADPH + 6 H+
2 fructose-6P + 1 glyceraldehyde-3P
OXIDATIVE PHASE
NON-OXIDATIVE PHASE
OVERALL EQUATION
Em 1963, P. Roy Vagelos, A. W. Alberts and D. B. Martin retomaram a questão levantada por Brady e Gurin desde 1952 de que alguns ácidos tricarboxílicos como o citrato poderiam estimular a síntese de ácidos graxos. A acetil-CoA carboxilase purificada por Vagelos e cols em 1963, foi submetida a centrifugação em gradiente de 5 a 20% de sacarose que separa proteínas pela velocidade de sedimentação. Na experiência mostrada abaixo, enzimas controle) e tratadas previamente com citrato foram centrifugadas em gradiente e a atividade das amostras coletadas foi ensaiada. Na figura, a fração número zero corresponde a fração coletada no fundo do tubo. Qual o significado destes resultados? O que podemos dizer sobre os efeitos do citrato sobre as características físicas e cinéticas da acetil-CoA carboxilase?
pré-incubada com citratopré-incubada
sem citrato
pyruvate
citrate
acetyl-CoA
oxaloacetate
palmitate
ACC
FAS
malonyl-CoA
acetyl-CoA
citrate
CO2
G6P
glucose
F6P
F1.6BP
G3P
pyruvate
DHAP
ribulose-5-P
NADP+
NADPH
CO2
glycogen
+
-PFK1
malate
LIVERADIPOSE TISSUEMAMMARY GLAND
SKELETAL MUSCLEHEART
fatty acid
acyl-CoA
FAS
TAG
malonyl-CoA
malonyl-CoA
acetyl-CoA
citrate acyl-CoA
acetyl-CoA
malonyl-CoA
CITRATE LYASE
acetyl-CoA
pyruvate
glucose
-OXYDATION
GLYCOLYSIS
citrate
CITRATE LYASE
OAA
ACC1
ACC2ACC2
TCAcitrate
TCAcitrate
CPT
malato
malato
OAA
F1,6BP
G3P
pyruvate
DHAP
glucose glycerol
glycerol-3P
citrateacetyl-CoA
malonyl-CoA
fatty acyl-CoA
phosphatidic acid
DAG TAG
VLDL
pyruvate
acetyl-CoACO2
CO2
citrate
fatty acid
F1,6BP
G3P
pyruvate
DHAP
glucose
glycerol-3P
citrate
fatty acyl-CoA
phosphatidic acid
DAG
TAG
pyruvate
acetyl-CoACO2
CO2
citrate
fatty acid
TAG
TAG
TAG
TAG
TAGTAG
TAG
CoA
CoA CoA
CoA
PiPi
HEPATOCYTE ADIPOCYTE
GLYCEROL KINASE
GLYCEROL-3P DEHYDROGENASE
GLYCEROL-3P DEHYDROGENASE
FATTY ACYL-CoA SYNTHETASE
FATTY ACYL-CoA SYNTHETASE
ACYL TRANSFERASE
ACYL TRANSFERASEACYL
TRANSFERASE
ACYL TRANSFERASE
CoA
glucose glycerol
glucose
IDL
LD
F1,6BP
G3P
pyruvate
DHAP
glucose glycerol
glycerol-3P
citrateacetyl-CoA
malonyl-CoA
fatty acyl-CoA
phosphatidic acid
DAG TAG
VLDL
pyruvate
acetyl-CoACO2
CO2
citrate
pyruvate
acetyl-CoACO2
CO2
citrate
fatty acid
F1,6BP
G3P
pyruvate
DHAP
glucose
glycerol-3P
citrate
fatty acyl-CoA
phosphatidic acid
DAG
TAG
pyruvate
acetyl-CoACO2
CO2
citrate
fatty acid
TAG
TAG
TAG
TAG
TAGTAG
TAG
CoA
CoA CoA
CoA
PiPi
HEPATOCYTE ADIPOCYTE
GLYCEROL KINASE
GLYCEROL-3P DEHYDROGENASE
GLYCEROL-3P DEHYDROGENASE
FATTY ACYL-CoA SYNTHETASE
FATTY ACYL-CoA SYNTHETASE
ACYL TRANSFERASE
ACYL TRANSFERASEACYL
TRANSFERASE
ACYL TRANSFERASE
CoA
glucose glycerol
glucose
IDL
LD
Basta não comer gordura para não engordar e reduzir o colesterol?