Professional Documents
Culture Documents
Some enzymes have lifetimes ranging from several days to months - Constitutive Enzymes Constitutive Enzymes - are present in constant concentration in the cell p - concentration does not change with changes in metabolic state or environment of cell - are usually enzymes of central metabolic pathways (glycolysis, citric acid cycle, etc.).
4
Metabolism in Fasting and starvation Diabetes mellitus Cellular Protein turnover, the proteasome and autophagy Intracellular trafficking of proteins I Intracellular trafficking of proteins II Intracellular trafficking and disease 34. Revision
1
the completion of this lecture students should be able to: Discuss the functions and importance of cellular protein turnover Discuss the signals for protein degradation Explain the molecular mechanisms of cellular protein turnover
Some enzymes have very short lifetimes of minutes to hours. They are destroyed by proteases. Their short lifetimes are the consequence of either particular amino acid sequences which are very susceptible to attack by proteolytic enzymes or ubiquitination which makes them targets for specific proteases. Many of these short lived enzymes are inducible/repressible enzymes.
References:
Alberts et al Molecular Biology of the cell 5th ed (2008) 39 396, 782-786 B ology ( 008) 391-396, 78 786 Nelson and Cox, Lehninger Principles of Biochemistry, 5th ed (2008) 1107-1109
Inducible/repressible enzymes Enzymes for which the rate of synthesis can be E f h h h f h b increased (induction) or decreased (repression) by specific substances (metabolites, hormones, growth factors, etc.).
Half-life (h)
0.5 1.3 2.0 2.6 2 6 5.0
c-myc, c-fos, p53 oncogenes RNA polymerase 1 -Hydroxyl--methylglutarl coenzyme A reductase Deoxythymidine kinase Phosphoenolpyruvate carboxykinase
Slowly degraded
Aldolase Cytochrome b5 Glyceraldehyde-3-phosphate dehydrogenase Lactate dehydrogenase (isoenzyme 5) Cytochrome c 118 122 130 144 150
10
11
13
Lehninger Principles of Biochemistry
16
PEST (Pro, Glu, Ser, Thr), internal regions 10-60aas, rich in PEST create presumably structural domains which are recognised by specific proteases
half-life: < 2 h
17
Figure 6-94b Molecular Biology of the Cell ( Garland Science 2008)
Denatured Damaged by oxidation etc. Mutated, therefore not in correct tertiary/quaternary structure
15 18
22
Figure 6-90 Molecular Biology of the Cell ( Garland Science 2008)
The proteasome.
The proteasome resides in the cytosol and nucleus. An ATP dependent protease It is completely distinct from lysosomal systems for protein Alberts et al 5th ed degradation.
Fig 6.89 20
Figure 6-91b Molecular Biology of the Cell ( Garland Science 2008)
23
Proteasome structure
24
25
Figure 13-36 Molecular Biology of the Cell ( Garland Science 2008)
26
Figure 13-41 Molecular Biology of the Cell ( Garland Science 2008)
27
Figure 13-42 Molecular Biology of the Cell ( Garland Science 2008)