Oh my! Now what?

Alcohol Metabolism
EtOH
Peroxisome H2O2

Cytosol O2 ER
NAD+

CAT
H2O
Aminotriazole

NADPH NADP+

MEOS P450
NADH

ADH
Pyrazole

Acetaldehyde
NAD+ Mitochondrion

AlDH
NADH
Disulfiram Chlorpropamide (antabuse) (diabetes)

Acetate

Extra-hepatic tissue
Eric Niederhoffer SIU-SOM

Pathway Perturbations
Glc G6Pase G6P Cytosol F6P F16BPase PFK F16BP PEPCK OAA PEP NAD+ NAD+ PK Malate MDH OAA NADH GK

Ala
Asp ALT AST

MDH LDH Lactate Pyr NADH NADH

Malate

PDH NADH PC Acetyl CoA NAD+ MDH OAA NADH Malate

Cit ICit

Mitochondrion
Fum Suc S CoA NAD+ NAD+ aKGDH aKG IDH NADH

NADH

Malate-Aspartate Shuttle
(liver, kidney, heart)
IMS Matrix

Asp aKG AST Glu OAA NADH MDH NAD+ Mal

GT

Asp

aKG
AST Glu OAA NADH MDH NAD+ MaT Mal CI

Glycerol-3-Phosphate Shuttle
(skeletal muscle, brain)
IMS Matrix

NAD+

G3P FAD G3PDH

NADH

DHAP

FADH2

CIII

Review Questions

How is ethanol detoxified (enzymes, cofactors, products, location)? Which metabolic pathways are affected by alcohol-derived NADH (enzymes, metabolites)? How does the cell process NADH?

Descoberta do citocrmio P 450

1955 artigo de Alxerod Detoxication of drugs and other foreign compounds by liver microsomes. BRODIE BB, AXELROD J, COOPER JR, GAUDETTE L, LA DU BN, MITOMA C, UDENFRIEND S. Science. 1955 Apr 22;121(3147):603-4.

1958 evidencia da formao do complexo com CO 1964 1985 estrutura 3D de um citocrmio de Pseudomonas putida

Cytochrome P450 (abbreviated CYP, P450, infrequently CYP450) is a very large and diverse superfamily of hemoproteins found in all domains of life.

The most common reaction catalysed by cytochrome P450 is a monooxygenase reaction, e.g. insertion of one atom of oxygen into an organic substrate (RH) while the other oxygen atom is reduced to water: RH + O2 + 2H+ + 2e ROH + H2O

O sistema citocrmio P-450 : relevncia no metabolismo e como bioremediador

Cytochrome P450 (abbreviated CYP, P450, infrequently CYP450) is a very large and diverse superfamily of hemoproteins found in all domains of life.
The most common reaction catalysed by cytochrome P450 is a monooxygenase reaction, e.g. insertion of one atom of oxygen into an organic substrate (RH) while the other oxygen atom is reduced to water: RH + O2 + 2H+ + 2e ROH + H2O

Citocromio P 450 reduced + Carbon monoxide

The name cytochrome P450 is derived from the fact that these are colored ('chrome') cellular ('cyto') proteins, with a "pigment at 450 nm", so named for the characteristic Soret peak
formed by absorbance of light at wavelengths near 450 nm when the heme iron is reduced and complexed to carbon monoxide

There are over 30 human P-450 isoenzyme systems that have been identified to date. The major ones responsible for drug metabolism are the CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2D6, CYP2E1, CYP3A4 and the CYP3A5-7.

Estrutura 3 D do Citocrmio P 450 oxidase

Componentes do sistema e funcionamento 1. oxidase 2. Na sntese de grupos hidroxilo 3. Na sntese de grupos carboxilos

Estrutura 3 D do Citocrmio P 450 oxidase

Uma protena de membrana

Almada Negreiros