Enzymes

Original Editor - Lucinda hampton

Top Contributors - Lucinda hampton and Kim Jackson  

Introduction

Enzyme mechanism 1.jpg

Enzymes are proteins that have a specific function. They speed up the rate of chemical reactions in a cell or outside a cell. Enzymes act as catalysts; they do not get consumed in the chemical reactions that they accelerate. Substrates are the substances on which enzymes act. To date, approximately 75,000 enzymes are thought to exist in the human body—all divided into three classes: metabolic enzymes that run our bodies, digestive enzymes that digest our food, and food enzymes from raw foods that start our food digestion[1]

Enzyme activation energy.png

Why Enzymes are needed:

  • There are thousands of reactions that take place in cells and these require energy. Since energy is always limiting in a living cell, cells have adopted enzymes as a way to conserve energy. Insufficient energy is a barrier to initiating the reaction. Only when there is a sufficient amount of energy, can the reactant overcome the energy barrier and proceed to form a product (this is called the activation energy).[2]
  • Enzymes are essential for respiration, digesting food, muscle and nerve function, among thousands of other roles[3].
  • Every day, trillions upon trillions of chemical reactions occur in our body to make essential metabolic processes occur. Without enzymes, most metabolic reactions would take much longer and would not be fast enough to sustain life[4].[5]

Enzymes are named by adding the suffix -ase to the name of the substrate that they modify (i.e., urease and tyrosinase), or the type of reaction they catalyze (dehydrogenase, decarboxylase). Some have arbitrary names (pepsin and trypsin)[6].

Examples of Enzymes

Creatine kinase (CK): the most widely used enzyme to diagnose and follow muscle disease. It is present in the highest concentrations in serum in response to muscle injury, is the most sensitive indicator of muscle injury, and is the best measure of the course of muscle injury (located on the inner mitochondrial membrane, on myofibrils, and in the muscle cytoplasm). It is involved in cellular energy storage and transfer via two major effects: It catalyzes the production of high-energy adenosine triphosphate (ATP) via transfer of a phosphate from creatine phosphate, which is the major storage reservoir of energy during muscle rest, to adenosine diphosphate (ADP)[7].

Digesting Enzymes.jpg

Digestive enzymes are released, or secreted, by the organs of the digestive system. These enzymes include proteases that digest proteins, and nucleases that digest nucleic acids. Eg:

  • Amylase, produced in the mouth. It helps break down large starch molecules into smaller sugar molecules.
  • Pepsin, produced in the stomach. Pepsin helps break down proteins into amino acids.
  • Trypsin, produced in the pancreas. Trypsin also breaks down proteins.
  • Pancreatic lipase, produced in the pancreas. It is used to break apart fats.
  • Deoxyribonuclease and ribonuclease, produced in the pancreas. They are enzymes that break bonds in nucleic acids like DNA and RNA.

The B-vitamins comprise a group of eight water soluble vitamins that perform essential, closely inter-related roles in cellular functioning, acting as co-enzymes in a vast array of catabolic and anabolic enzymatic reactions.

CoEnzymes and CoFactors

  1. A coenzyme or cosubstrate is a helper molecule that aids an enzyme in catalyzing a chemical reaction.
  • A coenzyme requires the presence of an enzyme in order to function. It is not active on its own.
  • While enzymes are proteins, coenzymes are small, nonprotein molecules. Coenzymes hold an atom or group of atoms, allowing an enzyme to work.
  • Examples: The B-vitamins group act as co-enzymes in a vast array of catabolic and anabolic enzymatic reactions. Their collective effects are particularly prevalent to numerous aspects of brain function, including energy production, DNA/RNA synthesis/repair, genomic and non-genomic methylation, and the synthesis of numerous neurochemicals and signaling molecules[8].
Vitamin B12.jpeg

2. Cofactors are inorganic species or at least nonprotein compounds that aid enzyme function by increasing the rate of catalysis.

  • Typically, cofactors are metal ions.
  • Some metallic elements have no nutritional value, but several trace elements function as cofactors in biochemical reactions, including iron, copper, zinc, magnesium, cobalt, and molybdenum. Some trace elements that appear to be important for nutrition do not appear to act as cofactors, including chromium, iodine, and calcium[9].
  • Many vitamins are cofactors which help enzymes to catalyze reactions, such as the production of important proteins. eg. Vitamin C is a cofactor for the production of the connective tissue collagen. This is why people who get scurvy (severe form of vitamin C deficiency) may experience connective tissue problems such as muscle weakness, muscle soreness, and even unexplained bleeding as the connective tissues of blood vessels cannot be replaced[10].

Enzymes in Disease and Diagnosis

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Over the years, enzymes have emerged as critical regulators of human diseases. In addition, as biomarkers, some enzymes often present consequential cue about the disease state due to their corresponding altered pattern in tissues and serum. A vast embodiment of data from experimental research in model organisms and humans has ensured the clinical utilization of specific enzymes as an evidence-based strategy in disease prevention and diagnosis[11].

A number of diseases occur or can manifest due to insufficient quantities or elevated levels of specific enzymes including:

  • G6PD Deficiency: Of all known enzyme deficiencies in humans, glucose-6-phosphate dehydrogenase, or G6PD, deficiency is the most common throughout the world. Without enough G6PD, red blood cells are more vulnerable to breaking down, and hemolytic anemia can result. Those with this deficiency may not show any symptoms, or they can experience anemia with back pain, abdominal pain or jaundice when exposed to stressors such as infection[12].
  • The results of a cardiac enzyme test can indicate if someone had a heart attack. Levels of troponin are normally so low that this enzyme is undetectable in the blood. If someone’s cardiac enzyme test comes back positive for troponin, they have likely had a heart attack or injury to the heart. These results can help a doctor to assess the level of damage caused by the heart attack. The more troponin found in the blood, the more damaged the heart generally is. Doctors and scientists measure troponin in nanograms per milliliter (ng/mL). The more nanograms per milliliter found in the blood, the higher the likelihood of a heart attack.[13]
  • Congenital Adrenal Hyperplasia: Inherited disorder.
  • Gaucher’s Disease
  • Wilson's Disease
  • Exocrine pancreatic insufficiency (EPI) occurs when the pancreas can’t make or release enough digestive enzymes to break down food and absorb nutrients. EPI is a major complication of cystic fibrosis. Cystic fibrosis is the second most common cause of EPI, after chronic pancreatitis. It occurs because the thick mucus in the pancreas blocks pancreatic enzymes from entering the small intestine[14].
  • Metabolic myopathies (rare genetic diseases that affect metabolism): People with metabolic myopathies lack certain enzymes involved in providing energy that helps muscles contract eg. McArdle disease is due to a lack of enzyme that assists in carbohydrate metabolism, Mitochondrial metabolic myopathy is another type that results from a lack of a particular enzyme normally present in the mitochondria[15].

Enzymes as Drugs

Antibiotics.jpg

Human enzymes are

  • Commonly targeted for pharmacological intervention in many diseases.
  • Attractive targets for drug therapy because of their essential roles in life processes and in pathophysiology (a survey reported in 2002 found that nearly half (47%) of all marketed small molecule drugs inhibit enzymes as their molecular target). NB A small molecular drug is any organic compound that affects a biologic process with a relatively low molecular weight, below 900 daltons[16].

Examples

  • Chemotherapy is the strategic use of chemicals, ie drugs, to destroy infectious microorganisms or cancer cells without causing excessive damage to the other, healthy cells of the host. Many well-established chemotherapeutic drugs function by inhibiting a critical enzyme in the cells of the invading organism.
  • An antibiotic is a compound that kills bacteria; it may come from a natural source such as molds or be synthesized with a structure analogous to a naturally occurring antibacterial compound. Many of them work by effectively inhibiting a variety of enzymes essential to bacterial growth.
  • Penicillin functions by interfering with the synthesis of cell walls of reproducing bacteria. It does so by inhibiting an enzyme (transpeptidase) that catalyzes the last step in bacterial cell-wall biosynthesis. The defective walls cause bacterial cells to burst. Human cells are not affected because they have cell membranes, not cell walls.[17]
  • Prescription pancreatic enzyme products, used to treat pancreatic insufficiency eg such as protease, pancrelipase, and pancreatic amylase.
Enzymes OTC.jpg

The use of enzyme supplements in general seems to be increasing, both by patients seeking to treat conditions or symptoms and by consumers seeking to enhance general health.

  • Include: bromelain, papain, trypsin, and chymotrypsin, as well as numerous combination products
  • The historical and preclinical data on enzymes are intriguing regarding digestion, anti-inflammatory effects, and anticancer properties.
  • Emerging clinical data seem to support many of these purported benefits.
  • However, as with many dietary supplements, the existing research is generally challenged by methodologic weaknesses, small sample sizes, heterogeneity of product, and lack of uniform outcome measures[18].
  • Despite this advertisements like the following are widely touted eg "Enzyme treatments for curing arthritis have by far produced positive results. The use of proteolytic enzymes such as serrapeptase has showed that such enzymes are capable of dissolving dead or scar tissues without harming the healthy living tissues. It is therefore a much safer alternative for steroidal and non steroidal inflammatory drugs or NSAIDs.  Also, it is rated as a safer option over exotic treatments such as D-penicillamine and methotrexate.  Such drugs and treatments can only provide temporary relief and may even prove lethal"[19].

References

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  3. Define biology Enzymes Available from:https://definebiology.com/enzymes-definition/ (last accessed 19.11.2020)
  4. Lewis T, Stone WL. Biochemistry, Proteins Enzymes. InStatPearls [Internet] 2020 Feb 8. StatPearls Publishing.Available from:https://www.ncbi.nlm.nih.gov/books/NBK554481/ (last accessed 19.11.2020)
  5. https://www.papertrell.com/apps/preview/The-Handy-Biology-Answer-Book/handy%20answer%20book/How-many-enzymes-are-in-the-human-body/001137031/content/SC/52caff2582fad14abfa5c2e0_default.htmlBasics of Biology Enzymes Available from: (last accessed 20.11.2020)
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  8. Kennedy DO. B vitamins and the brain: mechanisms, dose and efficacy—a review. Nutrients. 2016 Feb;8(2):68.Available from:https://www.mdpi.com/2072-6643/8/2/68/htm (accessed 19.11.2020)
  9. The thought co. Coenzymes Available from:https://www.thoughtco.com/definition-of-coenzyme-and-examples-604932
  10. Biol dictionary Cofactor Available from: https://biologydictionary.net/cofactor/(last accessed 19.11.2020)
  11. Ullah MF, Bhat SH, Tariq M, Abuduhier FM. Clinical Significance of Enzymes in Disease and Diagnosis. InBiocatalysis 2019 (pp. 213-231). Springer, Cham.Available from:https://link.springer.com/chapter/10.1007%2F978-3-030-25023-2_11 (accessed 19.11.2020)
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  13. Medical news today What do elevated cardiac enzyme levels mean? Available from:https://www.medicalnewstoday.com/articles/321684 (last accessed 20.11.20)
  14. healthline The Connection Between Exocrine Pancreatic Insufficiency and Cystic Fibrosis Available from:https://www.healthline.com/health/exocrine-pancreatic-insufficiency/connection-between-epi-and-cystic-fibrosis (last accessed 20.11.2020)
  15. John Hopkins Myopathies Available from:https://www.hopkinsmedicine.org/health/conditions-and-diseases/metabolic-myopathy (accessed 19.11.20200
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  19. Proteolytic enzymes Available from:http://www.takebackyourhealth.com/Proteolytic-Enzymes-A-Potential-Cure-for-Arthritis.html