Overview

Definition

An enzyme is a protein that presents active sites which perform reactions by decreasing the activation energy of that reaction.

Enzyme characteristics

• Complex protein and biocatalyst (catalyst of biological origin)
• Remains unchanged after the reaction
• Identified by the presence of the suffix “-ase” (e.g.,lactate dehydrogenaseLactate DehydrogenaseOsteosarcoma)
• Highly specific for particular substrates and products:
  • Substrate (S): a substance upon which the enzyme acts
  • Enzyme-substrate (ES) complex: temporary molecule formed by the non-covalent binding of the enzyme and substrate via:
    • Ionic interactions: connections between charged molecules
    • Hydrophobic interactionsHydrophobic interactionsDNA Types and Structure
    • Van der Waals forcesVan der Waals forcesDNA Types and Structure: weak intermolecular attractions between uncharged molecules
    • Hydrogen bondingHydrogen bondingA low-energy attractive force between hydrogen and another element. It plays a major role in determining the properties of water, proteins, and other compounds.DNA Types and Structure
  • Product (P): molecule created by the enzymatic reaction
• pHpHThe quantitative measurement of the acidity or basicity of a solution.Acid-Base Balance and temperature may alter enzyme function.

Active site

• Area of an enzyme that binds to specific substrate molecules in order to facilitate a reaction
• Consists of binding and catalytic sites
• Binding sites: the area where the the substrate binds
• Catalytic site:the area that reduces the activation energy (energy required for a reaction to proceed)

Enzyme Specificity

• Substrate specificity: Each enzyme can convert only one particular substrate. This is based on the “induced-fit” model, in which the binding site of the enzyme changes to match a particular substrate.
• Stereospecificity: Substrates must be a specific isomer (e.g.,lactate dehydrogenaseLactate DehydrogenaseOsteosarcoma can only convert L-lactate topyruvatePyruvateDerivatives of pyruvic acid, including its salts and esters.Glycolysis and not its mirror image, D-lactate).
• Group specificity: Enzymes react with a specific chemical group (e.g., an amino group) located on the substrate.
• Reaction specificity: Each enzyme can catalyze only a specific type of reaction (e.g.,hydrolysisHydrolysisThe process of cleaving a chemical compound by the addition of a molecule of water.Proteins and Peptides).

Classification

Enzyme naming

The first part of the name describes the substrate. The last part describes the enzyme function. The first part will describe the product if the following are true:

• The product is biochemically important (e.g.,pyruvate kinasePyruvate kinaseAtp:pyruvate 2-o-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (l, r, m1, and m2).Glycolysis).
• The enzyme is in the ligase category outlined in the table below (e.g.,glutamine synthetaseGlutamine synthetaseSynthesis of Nonessential Amino Acids).
• An enzyme with the same function already exists and acts upon the substrate (e.g.,pyruvatePyruvateDerivatives of pyruvic acid, including its salts and esters.Glycolysis dehydrogenase andlactate dehydrogenaseLactate DehydrogenaseOsteosarcoma).

Enzyme classification

Isoenzymes, Coenzymes, and Prosthetic Groups

Enzymes can be modified in common ways to allow different organs to have the same activities or for substances outside of the substrate/enzyme/product sequence to influence enzymes.

Isoenzymes

• Catalyze the same kinds of reactions, but differ slightly in their structure (differentamino acidAmino acidAmino acids (AAs) are composed of a central carbon atom attached to a carboxyl group, an amino group, a hydrogen atom, and a side chain (R group).Basics of Amino Acids sequence) and in the organs on which they act
• Example:glycogen phosphorylaseGlycogen phosphorylaseAn enzyme that catalyzes the degradation of glycogen in animals by releasing glucose-1-phosphate from the terminal alpha-1, 4-glycosidic bond. This enzyme exists in two forms: an active phosphorylated form ( phosphorylase A) and an inactive un-phosphorylated form (phosphorylase B). Both A and B forms of phosphorylase exist as homodimers. In mammals, the major isozymes of glycogen phosphorylase are found in muscle, liver and brain tissue.Glycogen Metabolism in the muscles vs. α-glucosidase in the heart

Coenzymes

• Small auxiliary molecules often needed to start the enzymatic reaction:
  • These molecules have the capacity to attach/detach to the enzyme.
  • Serve a variety of functions (e.g., electron transfer, transfer of organic materials)
  • Vitamins often serve as precursors to many organic cofactors.
• Reusable (not consumed in the reaction)

Prosthetic groups

• Specific non-polypeptide units firmly bound to the enzyme and required for the biological function of some enzymes
• These molecules are permanently attached to the enzyme.

Clinical Relevance

The following conditions are caused by an enzymatic deficiency:

• Glucose-6-phosphate dehydrogenaseGlucose-6-phosphate dehydrogenasePentose Phosphate Pathway deficiency: inherited in anX-linked recessiveX-Linked RecessiveDuchenne Muscular Dystrophy manner. Can cause episodic intravascularhemolytic anemiaHemolytic AnemiaHemolytic anemia (HA) is the term given to a large group of anemias that are caused by the premature destruction/hemolysis of circulating red blood cells (RBCs). Hemolysis can occur within (intravascular hemolysis) or outside the blood vessels (extravascular hemolysis).Hemolytic Anemia when triggered by infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease, certain medication, stress, or foods such as fava beans, with all the symptoms and signs ofhemolytic anemiaHemolytic AnemiaHemolytic anemia (HA) is the term given to a large group of anemias that are caused by the premature destruction/hemolysis of circulating red blood cells (RBCs). Hemolysis can occur within (intravascular hemolysis) or outside the blood vessels (extravascular hemolysis).Hemolytic Anemia such asjaundiceJaundiceJaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin.Jaundice, pallor,dyspneaDyspneaDyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary).Dyspnea,fatigueFatigueThe state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.Fibromyalgia, andtachycardiaTachycardiaAbnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia.Sepsis in Children. It can also produceneonatal jaundiceNeonatal jaundiceYellow discoloration of the skin; mucous membrane; and sclera in the newborn. It is a sign of neonatal hyperbilirubinemia. Most cases are transient self-limiting (physiological neonatal jaundice) occurring in the first week of life, but some can be a sign of pathological disorders, particularly liver diseases.Jaundice in newborns.
• GalactosemiaGalactosemiaGalactosemia is a disorder caused by defects in galactose metabolism. Galactosemia is an inherited, autosomal-recessive condition, which results in inadequate galactose processing and high blood levels of monosaccharide. The rare disorder often presents in infants with symptoms of lethargy, nausea, vomiting, diarrhea, and jaundice.Galactosemia: most common and severe form ofgalactosemiaGalactosemiaGalactosemia is a disorder caused by defects in galactose metabolism. Galactosemia is an inherited, autosomal-recessive condition, which results in inadequate galactose processing and high blood levels of monosaccharide. The rare disorder often presents in infants with symptoms of lethargy, nausea, vomiting, diarrhea, and jaundice.Galactosemia. Produced due to a deficiency of galactose-1phosphatePhosphateInorganic salts of phosphoric acid.Electrolytes uridyltransferase. Presents days after birth with clinical manifestations such aslethargyLethargyA general state of sluggishness, listless, or uninterested, with being tired, and having difficulty concentrating and doing simple tasks. It may be related to depression or drug addiction.Hyponatremia,failure to thriveFailure to ThriveFailure to thrive (FTT), or faltering growth, describes suboptimal weight gain and growth in children. The majority of cases are due to inadequate caloric intake; however, genetic, infectious, and oncological etiologies are also common.Failure to Thrive,jaundiceJaundiceJaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin.Jaundice, and other features ofliverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood.Liver: Anatomy injury
• Chronicgranulomatous diseaseGranulomatous diseaseA defect of leukocyte function in which phagocytic cells ingest but fail to digest bacteria, resulting in recurring bacterial infections with granuloma formation. When chronic granulomatous disease is caused by mutations in the cybb gene, the condition is inherited in an X-linked recessive pattern. When chronic granulomatous disease is caused by cyba, ncf1, ncf2, or ncf4 gene mutations, the condition is inherited in an autosomal recessive pattern.Common Variable Immunodeficiency (CVID): chronic disorder characterized by granuloma formation. Phagocytic cells are unable to producebactericidalBactericidalPenicillins superoxide due to a defect in thenicotinamide adenine dinucleotideNicotinamide adenine dinucleotideA coenzyme composed of ribosylnicotinamide 5′-diphosphate coupled to adenosine 5′-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH).Pentose Phosphate PathwayphosphatePhosphateInorganic salts of phosphoric acid.ElectrolytesoxidaseOxidaseNeisseria in the cells.
• Lysosomal storage diseases:a group of genetic metabolic disorders caused by lysosomal defects that result in an accumulation of undigested metabolites and cellular death
  • Gaucher’s disease: inherited disorder that leads to the accumulation of undegraded glycolipid substrates in cells due to a deficiency of acid β-glucosidase
  • Krabbe’s disease: Also known as globoid cell leukodystrophy, this condition is produced due to a deficient activity of thegalactocerebrosidaseGalactocerebrosidaseAn enzyme that hydrolyzes galactose from ceramide monohexosides. Deficiency of this enzyme may cause globoid cell leukodystrophy.Krabbe Disease, which produces an accumulation of galactosylceramide.
  • Tay-Sachs diseaseTay-Sachs diseaseTay-Sachs disease is an autosomal recessive lysosomal storage disorder caused by genetic mutations in the hexosaminidase A (HEXA) gene, leading to progressive neurodegeneration. Classic symptoms in infants include rapid degeneration of cognitive and neuromuscular abilities, progressive blindness, and a macular cherry-red spot on physical examination.Tay-Sachs Disease: Produced due to a deficiency ofhexosaminidase AHexosaminidase AA mammalian beta-hexosaminidase isoform that is a heteromeric protein comprised of both hexosaminidase alpha and hexosaminidase beta subunits. Deficiency of hexosaminidase A due to mutations in the gene encoding the hexosaminidase alpha subunit is a case of Tay-sachs disease. Deficiency of hexosaminidase A and hexosaminidase B due to mutations in the gene encoding the hexosaminidase beta subunit is a case of Sandhoff disease.Tay-Sachs Disease, thisautosomal recessiveAutosomal recessiveAutosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited.Autosomal Recessive and Autosomal Dominant Inheritance lipid storage disorder may causeblindnessBlindnessThe inability to see or the loss or absence of perception of visual stimuli. This condition may be the result of eye diseases; optic nerve diseases; optic chiasm diseases; or brain diseases affecting the visual pathways or occipital lobe.Retinopathy of Prematurity,hypotoniaHypotoniaDuchenne Muscular Dystrophy, progressive cognitive decline, andseizuresSeizuresA seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized.Seizures.

References

1. Abdelmonem, B. H., Elbaz, R. A., & Elnagdy, S. (2024).Decoding the role of CYP450 enzymes in metabolism and disease: A comprehensive review.Biomedicines, 12(7), 1467.https://doi.org/10.3390/biomedicines12071467
2. Berg, J. M., Tymoczko, J. L., Gatto, G. J., & Stryer, L. (2023).Biochemistry (10th ed.). W. H. Freeman and Company.
3. Kuddus, M., Zaheer, M. R., & Roohi. (2024).Cold‐active microbial enzymes and their biotechnological applications. Microbial Biotechnology, 17(4), e14467.https://doi.org/10.1111/1751-7915.14467
4. Murray, R. K., Bender, D. A., Botham, K. M., Kennelly, P. J., Rodwell, V. W., & Weil, P. A. (2022).Harper’s illustrated biochemistry (32nd ed.). McGraw-Hill Education.
5. Nelson, D. L., & Cox, M. M. (2021). Lehninger principles of biochemistry (8th ed.). W. H. Freeman and Company.
6. Reetz, M. T., Garcia-Borràs, M., & Fasan, R. (2024).Engineered enzymes for the synthesis of pharmaceuticals and other high-value products.Nature Synthesis, 3(1), 19–32.https://doi.org/10.1038/s44160-023-00417-0
7. UpToDate. (2025, May 20).Rare RBC enzyme disorders.https://www.uptodate.com/contents/rare-rbc-enzyme-disorders