9.11 Enzyme Regulation and Bioenergetics

Catabolic pathway

Enzymes in pathway that breaks down molecules and release energy

Anabolic pathway

Enzymes in pathway that can make complex biomolecules from small precursors

Metabolic pathways consists of ______ _________ _______, which is why _______ _____ are needed

Numerous interconnecting pathways; regulatory enzymes

Regulatory enzymes

Responds to certain signals and reduces/increases catalytic activity

How are unfavorable reactions driven forward in pathways

More favorable reactions within the pathway will help drive the unfavorable reaction forward

How are pathways regulated

Substrates or products of one step can interact with a pathway enzyme to affect activity (down/upregulated)

Which enzyme is often the regulatory enzyme

E1; the regulatory enzyme typically doesn’t follow Michaelis-Menten kinetics; often multi-subunit proteins

Modulation of regulatory enzymes

1. Allosteric enzymes: Reversible noncovalent binding of allosteric modulators or allosteric effectors

2. Reversible covalent modification

3. Binding of separate regulatory proteins

4. Removal of peptide segment by proteolytic cleavage

Positive vs negative regulators

Increases vs decreases activity

Homotrophic regulator enzymes

Substrate and modulators are identical

Heterotrophic regulator enzymes

Modulator is a molecule other than the substrate

Aspartate transcarbamoylase (ATCase)

Catalyzes the formation of carbamoyl aspartate, an early step in pyrimidine biosynthesis

Regulated via ATP concentration, High ATP = Activated (R-state), Low ATP/High CTP = Inactivated (T-state)

Typical activity of allosteric enzyme

Typically more S-shaped; Sigmoidal curve of a homotrophic enzyme; Activators makes curve more hyperbolic, inhibitors makes curve more sigmoidal

Reversible covalent modification

For example; protein (phosphorylase) kinases catalyzes the attachment of phosphoryl groups to Ser, Thr, Tyr, His; Phosphoprotein phosphatases/protein phosphatases will remove these groups

Zymogen

Inactive precursor that is cleaved to form active protease enzyme

Proprotein/proenzyme

Precursors that are cleaved to form other proteins

Regulatory cascade

Mechanism allows for greater sensitivity for a molecular signal and greater amplification of the resulting response

Example of regulatory cascade

Blood clot formation from exposure of collagen to blood