Enzymes – Structure, Function, Types and more

What are Enzymes?

Enzymes are biocatalysts that help to speed up the reactions in our body. These reactions can be biochemical and commercially important processes. Enzymes are not only important for our body but also important in industries.

Enzymes can be extracted from cells and also manufactured in industries. Enzymes play an important role in the commercially important process like insulin production, baking process and pharmaceuticals. They are used in assays for clinical, forensic and environmental purposes.

Enzymes used as catalysts are only required in low concentrations. They speed up the reaction without getting themself involved during the process.

Enzymes have trivial names (common names) that refer to the reaction they catalyse and have a suffix -ase. For example, oxidase, dehydrogenase and carboxylase.

However, there are also individual proteolytic enzymes that have the suffix of -in. Examples are trypsin, papain and chymotrypsin.

The International Union of Biochemistry set up the Enzyme Commission to name all the enzymes with a four-part Enzyme Commission (EC) number. The EC number is used in commercial products and is only allowed to use in the advised concentration and quantity.

Structure of enzyme

Enzymes that are based on amino acids are globular proteins with a size range of less than 100 to 2000 amino acid residues.

The amino acids are arranged as one or more polypeptide chains. They are folded or bent to form a three-dimensional structure. These structures constitute a small area called an active site. The active site is the region where the substrate binds and brings a conformational change.

How do enzymes work?

Enzymes do not alter the equilibrium of the reaction but they just fasten the reaction to attain equilibrium rapidly.

German chemist Emil Fischer suggested a hypothesis that enzyme specificity results from the complementary nature of the substrate and its active site. It was first proposed in the year 1894 and was known as Fischer’s ‘lock and key hypothesis’. The hypothesis stated that only a key of the correct size and shape fits into the keyhole of the lock. The key is referred to as the substrate, the keyhole as the active site and the lock as an enzyme.

Another model is named as the ‘induced-fit model’ of substrate and enzyme binding, in which the enzyme molecule changes its shape slightly to accommodate the binding of the substrate.

The principle that is commonly used is the ‘hand-in-glove model’. In this hypothesis, the hand and glove are broadly complementary in shape. The glove is moulded around the hand as it is inserted to provide a perfect match, whereas the hand remains rigid.

What do enzymes do?

Enzymes make the process easy. Enzymes are used in various cellular processes in our body.

Digestive System

Digestion is a process that involves mechanically and enzymatically breaking down the food for absorption into the bloodstream.

The food we eat contains macronutrients like fat, carbohydrates and proteins. These macronutrients are broken into molecules that can pass through the intestinal epithelium through the process of digestion. They then enter the bloodstream for the body to use it.

The enzyme action is promoted by hydrochloric acid (HCl), which is secreted by the liver and stomach.

Digestion involves mechanical and chemical digestion. In mechanical digestion, the food is broken into small pieces and then sent for chemical digestion.

In the chemical digestion process, there will be further degradation of the food particles by the enzymes. The molecular structure of the ingested particles is degraded in such a way that they can be easily absorbed into the bloodstream.

The enzymes present in the salivary and lingual glands digest the carbohydrates and fats. The enzymes present in the stomach digest proteins and the enzymes from the endocrine glands digest carbohydrates, proteins, lipids, DNA and RNA.

Chemical digestion starts from the mouth and the enzymes alpha-amylase or ptyalin break the food.

After the partial digestion of the food particles in the oral cavity, the partially digested food or bolus moves through the oesophagus and then to the stomach.

In the oesophagus, no digestion takes place. After the bolus reaches the stomach, again it undergoes mechanical and chemical digestion.

Peristaltic contraction breaks the food mechanically in the stomach. The goal of mechanical digestion is to reduce the food particles below 2mm. This process is called grinding.

The process of grinding, propulsion and retropulsion takes place in the stomach till the food particles are broken into small particles where they can be absorbed into the bloodstream. These are called migrating motor complexes (MMCs).

Effective digestion process involves both mechanical and enzymatic processes. Defect in any one of the process leads to nutritional deficiency and gastrointestinal pathologies.

From the gastrointestinal system, the nutrients like minerals, vitamins and protein enter the bloodstream.

DNA Replication

DNA replication copying of cell’s DNA to another. Replication is required for the growth or replication of the organism.

The DNA replication process is considered semi-conservative. During the replication process, two original strands act as a template for the new complementary strand.

After the completion of the replication process, there will be two sets of identical DNA. Each contains one newly synthesised strand and one original strand.

For the replication of DNA certain enzymes like DNA polymerase, DNA primase, DNA helicase, DNA ligase and topoisomerase are required.

DNA replication is initiated when the enzyme helicase unwinds and unzips the double-stranded DNA and it forms a ladder-like structure.

Single-stranded binding (SSB) proteins attach to these loose strands to keep them from joining with the broken strands, which were broken by helicase.

When the nitrogenous base is exposed, a new complementary strand is created. The creation of a new strand is done by DNA polymerase with the help of primase.

The DNA polymerase binds to DNA molecules and connects the nucleotides in order to match the nitrogenous base with the original strand.

DNA polymerase can work in only one direction, which helps to synthesise one long strand of DNA. There are two types of strands leading and the lagging strand.

When a long DNA strand is unzipped by DNA polymerase and helicase it is called a leading strand. When small fragments of DNA molecules are replicated in opposite direction, where the helicase is unzipping, it is called a lagging strand.

Okazaki fragments are small chunks of replicated DNA that are present on the lagging strand. After the completion of the process by DNA polymerase, the enzyme ligase completes the final stages of the replication process.

The enzyme ligase repairs the sugar-phosphate backbone and the gaps in the Okasaki fragments are connected. After this process, the DNA gets back into the classic double helix structure. This indicates the completion of replication.

Liver Enzymes

The liver contains many enzymes that are involved in metabolism, immunity, digestion, vitamin storage and detoxification.

The liver comprises about 2% of the body’s weight. The liver gets a dual supply from the portal vein and hepatic artery.

The functional unit of the liver is called the lobule and depending on the function it is divided into 3 zones.

Zone I is the periportal region and it can regenerate easily because of its proximity to oxygenated blood and nutrients. Zone I plays a major role in the process of beta-oxidation, gluconeogenesis, cholesterol formation, bile formation and amino acid catabolism.

Zone II is the pericentral region and zone III plays a major role in detoxification, ketogenesis, glycolysis, lipogenesis, glycogen synthesis, glutamine formation and biotransformation of drugs.

Bile is produced by the liver that helps to excrete materials that are not excreted by the kidneys. It helps in the absorption and digestion of lipids by secretion of bile salts and acids.

The enzymes made by the liver are alkaline phosphatase (ALP), alanine transaminase, (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT).

Lactate dehydrogenase is released in the blood when the cells are damaged by any infection/disease or an injury.

When there is a fluctuation in the normal range of the enzymes it indicates liver disease.

Types of Enzymes

The enzymes are classified into six main categories. They are

• Oxidoreductases– Catalysis the oxidation/reduction process
• Transferases– Transfers the chemical group
• Hydrolases– Hydrolysis the chemical bonds 
• Lyases– Lyases function to cleave the chemical bonds by oxidation or hydrolysis
• Isomerases– It catalysis geometric and structural changes between isomers and
• Ligases– These join two compounds associated with the hydrolysis of a nucleotide triphosphate molecule.

Causes of Enzymes

Fabry disease

Fabry disease is an inherited disorder of glycosphingolipid (fat) metabolism. It results from the absence of markedly deficient activity of the lysosomal enzyme called alpha-galactosidase A (α-Gal A).

This disorder is placed under a category of diseases called lysosomal storage disorder. The deficiency is caused by mutations in the alpha-galactosidase A (GLA) gene which, instructs cells to make the alpha-galactosidase A (α-Gal A) enzyme.

Lysosomes are the primary digestive tract of cells. Enzymes within lysosomes break down or digest particular compounds and intracellular structures.

The primary function of alpha-galactosidase A (GLA) is to break down the complex sugar-lipid molecules called glycolipids specifically, globotriaosylceramide (GL-3 or Gb3).

The deficiency of the enzyme causes a continuous build-up of globotriaosylceramide and its related glycolipids in the cells. The build-up in the cells results in cell abnormalities and organ dysfunction, which may affect the heart and kidneys.

Fabry disease is classified into two major phenotypes. This type is described as ‘classic’ and type 2 as ‘later-onset’. Both the diseases may lead to renal failure or heart disease.

The symptoms of Fabry disease in males onset during the adolescent period. Symptoms include acroparesthesia (burning of hands and feet), decreased or absence of sweat production (hypohidrosis) and gastrointestinal problems.

Krabbe disease

Krabbe disease is a genetic disorder that is rare and it leads to death. It is an autosomal recessive disease, that occurs when there is a deficiency of the enzyme galactocerebrosidase (type of lysosomal storage disorder).

Psychosine, a toxic compound gets accumulated in the central and peripheral nervous system, which causes neurological symptoms.

Since the disease is fatal, a meticulous diagnostic and early treatment can be crucial. The mutation is noted on chromosome 14 which denotes lysosomal hydrolase known as galactosylceramide beta hydrolase (GALC).

The enzyme metabolises galactolipids in the central nervous system and peripheral nervous system. When there is a deficiency of the enzyme it causes an accumulation of the compound that is responsible for neurodegeneration.

The other name for Krabbe disease is globoid cell leukodystrophy. Krabbe disease is divided into categories based on age and symptoms.

• Early infantile type (0-13 months)
• Late infantile type (13-36 months)
• Juvenile type (3-16 years)
• Adult type (>16 years)

In Krabbe disease, 30 kilobases of gene deletion are reported according to a paper published in the National Library of Medicine titled “Krabbe Disease”.

The symptoms depend on age. When the disease occurs at the infantile stage, it is can be progressive and fatal by the age of 2.

The symptom progression is categorised into stages. In stage I, the growth is normal till 6 months. The symptoms are visible, after 6 months. The child develops hypersensitivity to touch, bright light or noise. Other symptoms like irritability, restlessness, vomiting and feeding difficulties can be seen.

In stage 2, there will be a visual strain, opisthotonic posturing and optic atrophy. Seizure is also reported to be a common symptom.

In stage 3, the symptoms develop and can result in blindness and deafness.

The symptoms of the late infantile disease can be seen during the 13-36 months. Symptoms include visual difficulty, irritability and abnormal gait. The mortality is usually by 6 years.

In the juvenile stage, mortality is reported at 10 years. Symptoms include abnormal gait, hyperactivity disorder, tremors and attention deficit.

During the late-onset disease symptoms like mood alteration, burning sensation in the hands and legs, seizures, deafness and psychomotor retardation are reported.

Maple syrup urine disease

Maple syrup urine disease (MSUD) is a rare metabolic disease that is caused due to an inborn error. The disease is reported to have abnormal activity of branched-chain alpha-ketoacid dehydrogenase complex, which results in irreversible neurocognitive deficits that can be fatal.

The complex should break down amino acids like valine, isoleucine and leucine. The defect in the branched-chain alpha-ketoacid dehydrogenase complex disrupts the metabolism of branched-chain amino acids.

This disruption leads to the accumulation of branched-chain amino acids in the plasma and the urine. The disease manifest in the infant stage and the newborn finds it difficult to thrive.

The symptoms of the disease include feeding difficulties, delay in development and maple syrup odour in the urine.

Early diagnosis and treatment are required to reduce the severity and complication of the disease. If left untreated it can lead to irreversible neurological damage and metabolic catastrophe.

Treatment for the disease includes close monitoring of branched-chain amino acids and dietary restrictions.

Functions of enzymes in the body

The primary function of the enzyme is considered to catalyse the process or a reaction. RNAs are capable of catalysing the reaction, but mostly enzymes are said to catalyse the process.

In the absence of an enzyme, a process or a reaction may take years to complete but in the presence of the enzyme the reaction is fastened to million folds and it completes in a fraction of a second.

Enzymes have two primary functions. They increase the rate of the reaction without themself being consumed in the reaction or altering the reaction permanently.

Secondly, they increase the reaction rate without altering the chemical equilibrium.

What can affect digestive enzymes

Exocrine pancreatic  insufficiency

Pancreatic exocrine insufficiency is a condition of the inability to digest the food due to the deficiency in the exocrine pancreatic enzymes. This results in maldigestion.

The damage to the cells that produce the enzymes causes exocrine pancreatic insufficiency. The deficiency can lead to complications like maldigestion and poor quality of life.

There will be a reduction of the pancreatic enzyme activity mainly pancreatic lipase. The activity of the enzymes will be below the threshold level required for digestive function.

The deficiency can be due to the insufficient secretion of pancreatic enzymes by the pancreatic acinar cells, inadequate pancreatic stimulation and insufficient mixing of pancreatic enzymes in food.

The clinical manifestation of patients with exocrine pancreatic insufficiency includes weight loss, flatulence, abdominal pain and steatorrhea.

The condition affects the quality of life and increases the risk of complications, motility risk and changes in bone density.

The cause of pancreatic insufficiency in adults is called chronic pancreatitis and in children, it is called cystic fibrosis.

Other causes of the disease include HIV/AIDS, diabetes mellitus, celiac disease, bariatric surgery, inflammatory bowel disease and genetic causes.

Excess alcohol consumption is also a cause of chronic pancreatitis. Chronic pancreatitis affects the pancreas and recurrent inflammation leads to the replacement of pancreatic tissues by fibrosis. As a result, both the endocrine and exocrine enzymes’ function will be affected.

The theories for the pathogenesis of chronic pancreatitis include toxic metabolic theory, obstructive theory, oxidative stress theory and necrosis-fibrosis hypothesis.

Cystic fibrosis is due to the mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The gene codes for cAMP-regulated anion channel

Exocrine pancreatic insufficiency is classified into three types mild, moderate and severe. In the mild insufficiency condition, reduced secretion of one or two enzymes with preserved bicarbonate and normal faecal fat is observed. In the moderate insufficiency condition, the above with impaired bicarbonate secretion occurs. In the severe condition, all of the above plus steatorrhea occurs.

Natural and chemical inhibitors

Digestive enzymes are important as they break down the food and help in digestion. The enzymes and protein speed up the reaction and aid digestion. The digestive enzymes manage complications like lactose intolerance to cystic fibrosis.

An estimate of 75% of people worldwide is affected by hypolactasia or decreased lactase activity in adulthood, according to a data published in the National Library of Medicine titled “Digestive Enzyme Supplementation in Gastrointestinal Diseases”.

Diet

The enzyme activity is affected by various factors like pH and the concentration of the food we eat. The enzymes work to their full efficiency under favourable conditions. Some foods we eat might alter the pH and dilute the digestive acids in our stomach.

As a result, the enzymes lose the ability to bind to the substrate. Foods such as mangoes, honey, papaya, avocados, bananas, kiwi and ginger improve the activity of digestive enzymes and help to maintain the digestive system at specific pH.

When to see a doctor

Enzyme dysfunction can cause complications like

• Belly pain
• Abdominal pain
• Diarrhoea
• Oily stools and
• Bloating

These symptoms can indicate some serious complications. Consult your doctor when your experience such symptoms.

Conclusion

Eat healthy food to maintain your digestive enzymes. Enzymes maintain bodily functions and promote cellular functions.

The enzymes also prevent many gastrointestinal tract problems and promote gut health. Natural foods like fruits and vegetables promote physical and mental health. Choose healthy food to stay in good health.

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