biochem - 6 - enzyme regulation

what is enzyme specificity?

the ability of an enzyme to catalyze only one particular reaction

what is the primary reason for enzyme specificity?

structural complementarity of enzyme and substrate

describe the characteristics of the bond between and enzyme and substrate

weak, primarily through H-bonds, ionic bonds, and van der waals interactions

describe the lock and key hypothesis

an early concept that considers the enzyme to resemble a lock, and a substrate a key

describe the induced fit hypotheisis

considers that the enzyme’s active site is modified upon binding substrate

• confirmation of the substrate also changes

• creates the ES intermediate complex

what factors influence enzyme activity

• conversion of product to substrate as product accumulates; this reverse reaction slows down the enzyme rate v = d[P]/dt

• availability of substrates and cofactors

• genetic controls of the amount of enzyme (gene induction or repression)

• covalent modification by the reversible attachment of chemical groups such as phosphate groups

• allosteric regulation: an activator or inhibitor binds to the enzyme at a site other than the active site

• specialized controls: zymogens, isozymes, and modulator proteins

what are zymogens?

inactive precursors of enzymes or other proteins that acquire full activity by specific cleavage of one or more peptide bonds of the protein

what are examples pf zymogens

• insulin: important metabolic regulator is generated by excision of a specific peptide from proinsulin

• proteolytic enzymes of the digestive tract: enzymes that break down diety proteins are synthesized as zymogens in the pancreas and stomach

• blood clotting factors: formation of blood clots results from the activation of zymogens of clotting factors; these function as proteases when activated

what are isozymes?

forms of an enzyme that differ in their quaternary structure, with different numbers of distinct polypeptide subunits

what are examples of isozymes?

• lactate dehydrogenase (LDH): exists as five different isozymes, depending on the numbers of two subunits A and B

  • A₄, A₃B, A₂B₂, AB₃, and B₄

  • different tissues express different isozyme forms, which vary in their enzymatic properties

what are modulator proteins?

proteins that bind to enzymes and thereby influence their activity

what is an example of a modulator protein?

cAMP-dependent protein kinase

• consists of catalytic subunits that are enzymatically active and regulatory subunits that are modulator proteins that bind to the C subunits and inhibit their activity

what is allosteric regulation?

activation or inhibition of enzyme activity through non-covalent binding of small molecules (metabolites) to a site different than the active site

what is an example of allosteric regulation?

A —enz 1→ B —enz 2→ C —enz 3→ D —enz 4→ E —enz 5→ F

• F, the final product, is an essential metabolite such as an amino acid or nucleotide

what is feedback inhibition?

the final product F binds to enzyme 1

A —enz 1→ B —enz 2→ C —enz 3→ D —enz 4→ E —enz 5→ F

• can be toxic to the cell to build up too much of F

• the cell shuts down the pathway

  • F binds specifically to enzyme 1

  • F has two functions: function in the cell, and function as an inhibitor for this pathway

• feedback inhibition is a type of noncompetitive inhibition, where an inhibitor binds to a site different than an active site

  • F is not able to participate in competitive inhibition because it has changed significantly from the initial molecule A, that it no longer fits into the specialized enzyme 1 active site

why is the plot of v vs [S] a sigmoid for allosteric ezymes? what is the shape of the same graph for a typical enzyme?

• multiple subunits of allosteric subunits

  • that participate in of cooperative binding

• typically hyperbolic

what are the three properties of allosteric enzymes?

• plots of v vs. [S] give sigmoid curves

• the feedback inhibitor F shows little structural similarity to the precursor A

• some molecules (allosteric effectors) are inhibitors, while others have a stimulatory (positive) influence

• multiple subunits

• allosteric effectors change the conformation of the subunit polypeptides or th esubunit interactions

what is the term for multiple subunits?

oligomeric

if an unknown enzyme is put in a tube, and a plot of v vs [S] gives an s-shaped curve, what can be said about the identity of the enzyme?

• multiple subunits

• allosteric