Good day, students. Today, we will be discussing another important category of enzymes- Oligomeric Enzymes. Let us therefore start to examine how oligomeric enzymes have structure, how they are active and why they make more contributions to multistep and complex biochemical processes.
Oligomeric Enzymes - Definition, Types, Examples, and Applications
Oligomeric Enzymes consist of more than one polypeptide chain, as compared to monomeric enzymes, which only consist of a single polypeptide chain. Oligomeric enzymes are made of 2 or more polypeptide subunits that combine to form a functional enzyme.
The polypeptide subunits of an oligomeric enzyme may be the same (homomeric) or different (heteromeric), and their relationships can often yield unique properties such as cooperativity and allosteric regulation. Hemoglobin (not an enzyme, but a protein), lactate dehydrogenase, and aspartate transcarbamoylase are examples of biologically significant oligomeric enzymes.
Definition of Oligomeric Enzymes
An oligomeric enzyme is defined as an enzyme consist of two or more polypeptide chains, called subunits and they are linked together by non-covalent interactions and disulfide bonds to form a functional quaternary structure.
The enzyme which consist of two or more polypeptide chains, they linked to each other by non-covalent interactions are known as oligomeric enzymes.
What are Oligomeric Enzymes?
- Oligomeric enzymes are enzymes that consist of two or more polypeptide chains (subunits) that make up an active catalytic unit.
- Each subunit can contain its own active site, while all subunits contribute collectively to enzyme activity.
- Each subunit of an oligomeric enzyme is linked to each others by non-covalent interactions and disulfide bonds.
- Oligomeric enzymes can be homooligomeric, where all the subunits are identical, or heterooligomeric, in which multiple subunits are different.
- Oligomeric enzymes are included in dimeric, trimeric, and tetrameric proteins.
- The molecular weight of oligomeric enzymes is usually in excess of 35000 KDa.
- The majority of known enzymes are oligomeric; for example, all of the enzymes involved in glycolysis possess either two or four subunits.
- The activity of oligomeric enzymes relies on protein-protein interactions between the subunits, unlike monomeric enzymes whose activity is intrinsic.
- Oligomeric enzymes have increased stability due to their quaternary structure, while their oligomeric state may prevent denaturation or dissolution more than monomeric enzymes.
- Oligomeric enzymes may also be less sensitive to changing conditions or be more robust and efficient.
- Examples of oligomeric enzymes include hemoglobin, aspartate transcarbamoylase (ATCase), and lactate dehydrogenase (LDH), Lactose synthase, and Tryptophan synthase, etc.
Example of Oligomeric Enzymes
1. Lactate dehydrogenase (LDH)
- Lactate dehydrogenase (LDH) is an oligomeric enzyme that is available in multiple forms. These forms catalyze the same reaction, albeit with different kinetic properties and with different linear sequences of amino acids.
- These forms of the same enzyme are known as isoenzymes or isozymes; they can be separated and studied by electrophoresis and other methods.
- LDH is one of the most studied examples of isoenzymes because it exists in five possible forms from vertebrate tissue.
- The LDH enzyme exists as a tetramer, a proteins composed of four subunits. The four subunits share a common purpose, but have unlike compositions and properties.
- In the heart, LDH exists as the H-form, which has the highest activity with low concentrations of pyruvate, (H₄).
- Skeletal muscle contains mainly the M-form, which has better activity with high concentrations of pyruvate, (M₄).
- In terms of structure, LDH consists of a molecular weight of approximately 140,000 Da, and the four subunits are approximately 35,000 Da each.
- Different genes encode the H and M subunits. The individual monomers are non-catalytic, and when they come together in groups of four, active tetrameric enzyme, and thus catalysis can occur.
- The H and M subunits can also mix in different amounts. Therefore, there can be five different isoenzymes: H₄ (LDH1), H₃M (LDH2), H₂M₂ (LDH3), HM₃ (LDH4), and M₄ (LDH5).
2. Aspartate Transcarbamoylase (ATCase)
- ATCase is an oligomeric enzyme that catalyzes the first committed step in the synthesis of pyrimidine nucleotides, turning carbamoyl phosphate and aspartate into carbamoyl aspartate.
- ATCase has catalytic and regulatory subunits, so it is a textbook example of allosteric regulation.
- ATCase displays sigmoidal kinetics that suggests substrate binding is cooperative across subunits.
- CTP serves as a feedback inhibitor of ATCase, while ATP serves as an activator, again balancing the pools of purine and pyrimidine nucleotides.
- The enzyme switches back and forth between a T (tense, inactive) state and the R (relaxed, active) state, depending on the binding of effectors.
- ATCase is also a model system with which to study enzyme regulation, cooperativity, and allosterism.
3. Lactose Synthase
- Lactose synthase is the enzyme complex responsible for synthesizing lactose in the mammary gland during lactation.
- It catalyzes the transfer of galactose from UDP-galactose to glucose, producing lactose.
- The enzyme consists of two subunits: β-1,4-galactosyltransferase (the catalytic subunit) and α-lactalbumin (the regulatory subunit).
- α-Lactalbumin alters the specificity of the galactosyltransferase, allowing the enzyme to use glucose as an acceptor.
- Its activity is hormonally regulated, primarily by prolactin during lactation.
- The various subunits of lactose synthase exemplify how protein–protein interactions can change enzyme specificity and biological function.
4. Tryptophan Synthase
- Tryptophan synthase is a multienzyme system/complex that promotes the last two steps in the biosynthesis of the amino acid tryptophan.
- It has two subunits: the α-subunit promotes the conversion of indole-3-glycerol phosphate to indole, while the β-subunit condensing indole with serine to form tryptophan.
- The enzyme exhibits substrate channeling, meaning that indole is passed directly from the α-site and not allowed to diffuse into solution.
- This substrate channeling has an increase in catalytic efficiency and prevents the loss of the elusive and unstable indole intermediate.
- In addition, tryptophan synthase is able to regulate and maintain the correct balance of amino acids, as well as prevent unnecessary tryptophan biosynthesis.
- Tryptophan synthase is also an important case study/model in enzymology because it allows for the establishment of the multienzyme model system and the coordination of multiple subunits.
Applications of Oligomeric Enzymes
- Oligomeric enzymes have tremendous applicatiions in every industry including Medicine and Diagnostics, Biotechnology, Pharmaceutical Industry, Research and Education.
- Their allostery (i.e. in terms of having symmetric and multiple active sites) makes them key regulators of metabolism; e.g aspartate transcarbamoylase in nucleotide synthesis.
- Have been used as biomarkers for studying both enzyme interventions and genetic disorders.
- They used in design of drugs for the treatment of metabolic disorders and cancer therapies.
- Used in fermentation, food processing and biofuel production, an area of concentration that relies heavily on enzyme stability and regulation.
- Provide insight on protein–protein interactions, enzyme mechanisms.