Anda di halaman 1dari 26

AULA 14

Regulao metablica : mecanismos moleculares Regulao metablica : mecanismos moleculares

REGULAO DE VIAS METABLICAS

E 1 etapa reguladora

REGULAO DE VIAS METABLICAS NAD+ NADH

REGULAO DE VIAS METABLICAS

E 1 etapa reguladora

REGULAO DE VIAS METABLICAS

Pi-

-Pi -Pi

3. Alterao covalente > fosforilao > activao ou inibio actividade de protena cinase ou de fosfatase

REGULAO DE VIAS METABLICAS

5. Alterao da quantidade de enzima regulao da expresso do gene que codifica para a protena

6. Carga energtica

7. Activao ou inactivao mediada por interaco protena / protena

REGULAO DE VIAS METABLICAS

Exemplos: 1. 2. 3. 4. 5. 6. 7. Citrato sintetase Gliceraldedo-3-fosfato desidrogenase Glicognio sintetase Fosfofructo-cinase 3- HMG-reductase Acetil-coA carboxilase Apo C / lipoprotena lipase

Acetil-CoA carboxilase CO2 Acetil-CoA Malonil-CoA ADP ATP oxaloacetato Existe em diversas formas que exibem actividades diferentes 1. - fosforilada 1. Conformao diferente

citrato

Fontes de cidos gordos


glucose palmitoil-CoA
Sintetase de cidos gordos

gliceraldedo-3-Pi

malonil-CoA
Acetil-CoA carboxilase

piruvato

acetil-CoA

piruvato acetil-CoA

Sntese de malonil-CoA

Regulao da acetil-CoA carboxilase ATP ADP P

activa

inactiva

P H2O citrato
Proteina cinase AMP dependente

P
parcialmente activa

Protena fosfatase 2A

citrato

AMP-cinase

Cataliza a fosforilao da Acetil-CoA carboxilase <> INACTIVAO activada por AMP <> baixa carga energtica

paragem da sntese de c.gordos Ocorre -oxidao de c.gordos

Aumento da conc. de ATP

inibio da AMP-cinase

recomeo da sntese de c.gordos

ATP ADP

activa

inactiva

H2O
Hipoglicemia

glucagon

inibio da fosfatase

REGULAO DE VIAS METABLICAS

E 1 etapa reguladora

As vias de sntese e de degradao so diferentes

SINAIS RECEPTORES

ALTERAES METABLICAS

GLUCAGON / EPINEFRINA
R

Estrutura de uma protena G trimrica

Diseases Associated with G Protein Coupled Receptor Mutations

Opsin Color blindness Rhodopsin Retinitis pigmentosa Rhodopsin Congenital night blindness V2 vasopressin Nephrogenic diabetes insipidus ACTH Familial ACTH resistance LH Familial male precocious puberty TSH Familial nonautoimmune hypertyroidism Ca2+ Familial hyperparathyroidism Thromboxane A2 Congenital bleeding

Protena tirosina cinase

Substrato + ATP

substrato-Pi + ADP

Protena tirosina fosfatase

Tyrosine kinases - catalyze transfer of a g-phosphate from ATP to the hydroxyl group on tyrosine residues of protein substrates.

Tyrosine

HO-

-CH2-C-COONH3+ H

Serine

HO-CH2-C-COONH3+ HO H

Threonine

CH3-C-C-COOH NH3+

Tyrosine Protein Phosphorylation


Eukaryotic cells coordinate functions through environmental signals soluble factors, extracellular matrix, neighboring cells. Membrane receptors receive these cues and transduce signals into the cell for appropriate response. Tyrosine kinase signalling is the major mechanism for receptor signal transduction. Tyrosine protein phosphorylation is rare (1%) relative to serine/thrreonine phosphorylation. TK pathways mediate cell growth, differentiation, host defense, and metabolic regulation. Protein tyrosine phosphorylation is the net effect of protein tyrosine kinases (TKs) and protein tyrosine phosphatases (PTPs).

Protein Tyrosine Kinases (TKs)


Receptor tyrosine kinases (RTK) insulin receptor EGF receptor PDGF receptor TrkA Non-receptor tyrosine kinases (NRTK) c-Src Janus kinases (Jak) Csk (C-terminal src kinase) Focal adhesion kinase (FAK)

Protein Tyrosine Phosphatases (PTPs)


Receptor-like or Transmembrane PTPs CD45 PTPa LAR Non-receptor or Cytoplasmic PTPs PTP1B SHP1 SHP2

Receptor Tyrosine Kinases

From Hubbard (2000) Annu. Rev. Biochem. 69,373.

Receptor Dimerization and Kinase Activation

From Hunter (2001) Nature 411,355.