Unit 4: Hydrolysis Reactions and Zinc Catalysis

A set of vocabulary-style flashcards based on lecture notes covering the role of zinc as a catalyst in hydrolysis reactions and enzymes such as Carbonic Anhydrase, Carboxypeptidase-A, and Liver Alcohol Dehydrogenase.

Lewis acid catalysis

A process where a metal ion like $Zn^{2+}$ polarizes a reactant to enhance its $\delta^+$ character or aids in the ionization of water to form a nucleophilic species like $[Zn–OH]^+$.

$$[Zn–OH]^+$$

A Lewis basic, nucleophilic species formed when $Zn^{2+}$ promotes the ionization of bound water, facilitating catalyzed hydrolysis reactions.

Ligand-field effects in $Zn^{2+}$

These do not apply because $Zn^{2+}$ is a $d^{10}$ ion with a fully filled d shell, allowing coordination geometry to change with no energetic penalty from changes in ligand field stabilization energy.

Kinetic inertness of $Zn^{2+}$

The property of $Zn^{2+}$ to form stable, firm bonds with N and S donors (such as histidine and cysteine side-chains), allowing for the anchoring of the metal ion to the protein active site.

Carbonic Anhydrase (CA)

An enzyme that catalyzes the hydrolysis of $CO_2$ to bicarbonate ($HCO_3^-$) with a rate enhancement of about $10^8$, making it one of the most efficient enzymes known.

Bicarbonate ($HCO_3^-$)

The highly water-soluble form of $CO_2$ produced by the action of Carbonic Anhydrase, allowing efficient use in photosynthesis or removal to the lungs.

$Zn^{2+}$ coordination in CA

The metal ion is coordinated by three histidine ($his$) residues with a water molecule at the 4th site.

$pK_a$ of CA-bound water

The value is approximately $7$, which is significantly lower than the $pK_a$ of $14$ for pure water, illustrating how $Zn^{2+}$ favors ionization to generate a nucleophile.

Carboxypeptidase-A (CBP–A)

A zinc-containing enzyme that catalyzes the hydrolysis of proteins and peptides into amino acids, specifically targeting the C-terminus.

CBP–A Substrate Preference

This enzyme is most effective for hydrolyzing peptides with aromatic side-chains at the C-terminus, such as phenylalanine, tryptophan, or tyrosine.

pH dependence of CBP–A

The enzyme exhibits a bell-shaped activity curve maximal under neutral conditions, with $pK_a$ values of $6.1$ and $9.0$.

Liver alcohol dehydrogenase (LADH)

A zinc-containing enzyme that oxidizes alcohol to acetaldehyde (ethanal) using $NAD^+$ as the oxidizing agent.

$NAD^+ / NADH$ pair

The natural oxidizing/reducing agent in cells where transformation involves a hydride transfer ($H^-$).

Role of Zinc in LADH

$Zn^{2+}$ binds and activates the alcohol substrate, anchors it in the correct orientation for hydride transfer, and favors its ionization to make the resulting alkoxide more electron-rich.

$Mg^{2+}$ vs. $Zn^{2+}$

While similar in size and charge, $Mg^{2+}$ is a $d^0$ ion and is less Lewis acidic and more labile (forming less firm bonds to N/S donors) than the $d^{10}$ $Zn^{2+}$ ion.