The Pancreas: Trypsin, Protein Digestion, and Pancreatitis
The Function of Trypsin
The pancreas is an important organ that performs multiple jobs. One of these jobs is to produce digestive enzymes, which enable us to obtain nutrients from food. Trypsin is a potent pancreatic enzyme. It's produced in an inactive form in the pancreas and is activated in the small intestine, where it digests protein. Unfortunately, under certain conditions trypsin is activated within the pancreas, where it may damage tissue and cause pancreatitis.
Digestive enzymes convert the molecules in food into smaller units that our body can absorb. Trypsin converts large and complex protein molecules into smaller and simpler molecules. Other enzymes in the small intestine then complete the digestion of the protein. If a significant amount of active trypsin collects in the pancreas, it may digest the proteins that are a normal part of pancreatic cells, causing potentially serious effects.
The pancreas is a long, narrow, and flat organ on the left side of the upper abdomen. It's located behind the stomach and in front of the spine. The head of the pancreas extends into the curve formed by the duodenum, which is the first part of the small intestine.
The pancreas is an unusual and versatile organ. It contains both endocrine and exocrine glands. An endocrine gland makes a hormone and secretes it into the bloodstream. An exocrine gland secretes its product (which is not a hormone) into a duct. The duct then transports the product to a different area.
Pancreatic hormones are secreted by patches of tissue known as pancreatic islets or islets of Langerhans. Two of these hormones are insulin and glucagon, which play an important role in regulating blood sugar. Digestive enzymes are produced by structures called acini, which are composed of acinar cells. The acini release their enzymes into a fluid known as pancreatic juice. The enzymes include inactive trypsin for digesting proteins, lipase for digesting fats, and pancreatic amylase for digesting starch.
The Pancreatic Duct
Digestive enzymes travel out of the pancreas in a passageway called the pancreatic duct. Cells lining the duct secrete sodium bicarbonate and water into the pancreatic juice. The sodium bicarbonate helps to provide the correct pH for enzyme activity in the small intestine.
The pancreatic duct transports the enzymes to the interior of the duodenum (the first part of the small intestine), where they do their job. Despite the vital role of the pancreas in digestion, food never enters it.
Amino acids are the "building blocks" of proteins. A short chain of amino acids is called a peptide. A longer chain is called a polypeptide. A protein contains one or more polypeptides arranged in a distinct and often complex shape. Enzymes are a type of protein.
Trypsinogen, Trypsin, and Protein Digestion
The inactive form of trypsin is known as trypsinogen. The inactivity is vital, since proteins are very important components of cells. If active trypsin is produced inside pancreatic cells, it will digest the cell's proteins unless it's inactivated or removed.
Even in a healthy person, a very small amount of trypsinogen is converted to trypsin within the acinar cells of the pancreas. There are safeguards in place to reduce trypsin formation and to prevent trypsin from damaging the pancreas, however. For example, trypsinogen is stored in protective, membrane-bound compartments inside the acinar cells. In addition, the acinar cells make chemicals that act as trypsin inhibitors by binding to trypsin molecules and inactivating them. Another important factor is the flow of liquid in the pancreatic duct, which helps to flush activated trypsin out of the pancreas and into the intestine.
When trypsinogen reaches the small intestine, an enzyme called enteropeptidase converts the trypsinogen to trypsin. Enteropeptidase is made by the intestinal lining, or the mucosa.
Trypsin belongs to a class of enzymes known as proteases. These enzymes break down proteins. Trypsin digests proteins from food into shorter peptides. Other enzymes made by the intestinal lining then break the peptides down into individual amino acid molecules. The amino acids are absorbed into the bloodstream through the lining of the small intestine.
The Lock and Key Theory of Enzyme Action
Trypsinogen is an enzyme precursor, or a zymogen. It's stored in acinar cells inside membrane-bound sacs called zymogen granules. The word zymogen is derived from the term enzyme generator.
Like all enzymes, trypsinogen has a section called the active site. This is the place where the reactant or substrate of an enzyme-controlled reaction joins to its enzyme. Once this union takes place, a chemical reaction happens and products are produced.
A zymogen such as trypsinogen is inactive because a peptide blocks its active site, preventing it from doing the job of an enzyme. This peptide is removed when the zymogen is activated.
Other zymogens exist in the body in addition to trypsinogen. For example, the pancreas also secretes chymotrypsinogen, which becomes chymotrypsin in the small intestine. Like trypsin, chymotrypsin digests proteins into peptides. Cells in the stomach lining release pepsinogen into the stomach cavity. Pepsinogen is activated by hydrochloric acid, becoming an enzyme called pepsin. Pepsin is a protease. The proteins involved in the blood clotting process are also zymogens. They are activated when we are wounded.
Acute and Chronic Pancreatitis
Rarely, a significant amount of trypsin collects in the pancreas. If the pancreas is unable to inactivate or remove this trypsin, the pancreas begins to digest itself. As a result, it becomes inflamed, a condition known as pancreatitis.
Pancreatitis may be acute or chronic. Acute pancreatitis arises suddenly and lasts for a short time (provided it's treated). It ranges from a relatively minor problem to a severe or even life-threatening disease. Chronic pancreatitis lasts for a long time or occurs repeatedly. The continuous or repeated damage to the pancreas may lead to the creation of fibrous scar tissue and the loss of function in the pancreas.
Symptoms of pancreatitis may include:
- abdominal pain, which may radiate to the back of the body
- abdominal pain that is worse after eating
- increased heart rate
In chronic pancreatitis, the stool may become oily. This condition is known as steatorrhea. It develops because lipase, the fat-digesting enzyme made in the pancreas, is no longer reaching the small intestine or is being sent to the intestine in inadequate amounts. As a result, the digestion of fat is greatly decreased. It doesn't stop, however, because lipase is also made in the mouth (lingual lipase) and stomach (gastric lipase). Someone with chronic pancreatitis may find that they lose weight without deliberately trying to do this.
Anyone with unexplained symptoms or ones that might indicate the presence of pancreatitis should visit a doctor for a diagnosis and treatment. Not all of the symptoms listed above may be present in someone with pancreatitis. In addition, the symptoms may indicate the presence of a different disorder.
The Passage of Bile
The liver produces a liquid called bile, which it sends to the gall bladder. Gallstones may form in the gall bladder or in the ducts that transport the bile. These gallstones may cause pancreatitis.
The passage of bile takes place as follows.
- The bile leaves the liver in the right and left hepatic ducts.
- These ducts join to form a single hepatic duct.
- The bile travels from the hepatic duct to the gall bladder through the cystic duct.
- Bile is stored in the gall bladder until it's needed to help fat digestion in the small intestine.
- The bile is sent to the small intestine through the cystic duct and the common bile duct.
- Some bile is sent directly from the liver to the small intestine through the common bile duct and never enters the gall bladder.
The two main types of gallstones are cholesterol stones and pigment stones. Cholesterol gallstones contain solid cholesterol and other substances. Pigment gallstones contain bilirubin, a yellow pigment.
Gallstones and Pancreatitis
The function of bile is to emulsify fat in the small intestine. During emulsification, fat is broken up into small droplets that are easier for lipase to digest. Bile contains water, bile acids or salts, cholesterol, inorganic salts, and a yellow pigment called bilirubin. Bilirubin is made in the liver from the breakdown of hemoglobin in old red blood cells. The bilirubin is excreted in the bile. Sometimes the dissolved substances in bile are too concentrated and solidify as solid lumps known as gallstones.
The most common cause of acute pancreatitis is the presence of gallstones. The common bile duct meets the pancreatic duct before reaching the duodenum. Gallstones transported in the bile duct can become lodged in front of the exit of the pancreatic duct, stopping the flow of pancreatic juice. When this happens, activated trypsin collects in the pancreas and pancreatitis may result.
Other Causes of the Disorder
Pancreatitis is caused not only by blockages in the pancreatic duct but also by the increased conversion of trypsinogen to trypsin within the pancreas and the decreased destruction of the trypsin that forms. Factors that may trigger trypsin formation include an increase in calcium concentration within the acinar cells and changes in pH. Mitochondrial damage may also play a role in triggering pancreatitis. The mitochondria are the organelles that produce energy for a cell.
Alcoholism is a common cause of pancreatitis. In some places, the number of people with pancreatitis linked to alcohol consumption is increasing. The repeated ingestion of alcohol increases the amount of trypsin in the pancreas, although how it does this is not yet understood.
Less common causes of pancreatitis include an abnormally high blood level of fats (hypertriglyceridemia) or calcium (hypercalcemia). Injury to the pancreas, some infections, and certain autoimmune conditions can also trigger pancreatitis. Some medications have been implicated in the disease as well. Sometimes the cause of the disorder is never discovered and it's said to be idiopathic.
Some Comment Treatments
A person with pancreatitis needs to be under a doctor's care. The doctor will diagnose the disease and prescribe appropriate treatment. The initial treatment often involves medication to relieve pain and procedures to help the pancreas heal itself, which may include temporary fasting and the administration of intravenous fluids.
Once the inflammation in the pancreas has subsided or is reduced, doctors generally try to correct or compensate for the condition that caused the pancreatitis. Gallstones may be removed, for example, or digestive enzymes prescribed. Dietary changes may be recommended and the patient may be given help to eliminate alcohol dependence. Occasionally, surgery may be necessary to remove fluid from the pancreas or to remove damaged tissue.
Investigating Pancreas Problems
Alcoholism is the second most common cause of pancreatitis. Despite this fact and the fact that many scientists are investigating pancreatitis, we don't know how alcohol causes the disease. In fact, there are many unanswered questions about pancreatitis that develops from any cause.
We still have a lot to learn about the pancreas and its activity. Studying the operation of the organ is an important endeavour because of the many ways in which it affects our lives. It would be wonderful to be able to correct pancreas problems both easily and quickly.
Trypsin facts from the European Bioinformatics Institute (EMBL-EBI)
Enzymes and the active site from the Khan Academy
Information about zymogens from the University of Washington
Pancreatitis information from the National Institutes of Health (NIH)
Symptoms and causes of pancreatitis from the Mayo Clinic
Facts about acute pancreatitis from the National Health Service (NHS)
Questions & Answers
© 2015 Linda Crampton