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IV Human Lipid Digestive Enzyme System Why Those suffering From Malnutrition and Those Less Than Two Years Old Can Benefit From Pre-digestion of Their Food Lipids are essential for health and normal development. They store energy in the body. Animals use triglycerides for energy storage because of its high caloric content as compared to the less compact carbohydrates utilized in plants. Lipids are major components of cell membranes. They are essential for normal brain development and maintenance as well as the neurological system in general. Linoleic and alpha-linoleic fatty acids are essential because they can not be synthesized by the normal human body. Cholesterol is the base molecule for bile salt production. Cholesterol is also a precursor of steroid hormones. Lipids are necessary to solubilize fat soluble vitamins for absorption. To understand lipid digestion, one of the things that needs to be understood is the process of emulsification (making an emulsion). An emulsion is the suspension of small globules of one liquid in a second liquid with which the first will not mix. An example is the mixture of vinegar and oil. In the intestines it is lipid and water. They will stay mixed only as long as they are stirred together unless an emulsifying agent or emulgent is present. Bile salts are emulgents. Bile acids are derivatives of cholesterol and are produced in the liver. These acids are constituents of bile which is produced in the liver and delivered to the duodenum (the first part of the small intestines). Here these bile acids are converted to bile salts by the alkaline or basic environment of the duodenum. Part of the bile salt is hydrophilic (attracts water) and part is hydrophobic (repels water). When bile salts come in contact with lipids, the hydrophobic parts bind into the lipid with the hydrophilic part remaining at the surface. This allows the break down of large aggregates or droplets of the lipid 1 into smaller and smaller droplets (micelles) in the water environment of the duodenum. For any given triglyceride volume, the smaller the micelles, the greater surface area of triglyceride available for digestive enzyme activity. About 90% of the bile acids are reabsorbed in the ileum, the last part of the small intestines. This is known as enterohepatic circulation. On the average, about 25 grams of bile salts are delivered to the small intestines daily. Therefore, about 2.5 grams of bile salts in the adult are produced by the liver on a daily basis and 22.5 grams are reabsorbed daily. Diarrhea significantly interferes with enterohepatic circulation, resulting in loss of bile salts and, therefore, over time, fat digestion. This results in increased diarrhea secondary to malabsorption of the lipids. A vicious cycle is created. Lipids are fats, oils, phospholipids, and sterols. Fats are triglycerides containing saturated fatty acids. Fats are generally solid at room temperature and are from animals. Oils are triglycerides containing mono or polyunsaturated fatty acids usually from plants and fish. They are liquid at room temperature. A triglyceride is made up of glycerol with three attached fatty acids: H2C – Fatty Acid l HC – Fatty Acid l H2C – Fatty Acid Phospholipids are triglycerides that have a fatty acid replaced by a phosphate linked fatty acid group. The major dietary sterol is cholesterol Lipases are enzymes that digest lipids. In the human, there are lipases which are produced in the tongue, the stomach and the pancreas. Stomach and lingual lipases hydrolyze or digest a limited number of fatty acids. The lipases produced by the pancreas are the 2 major lipases utilized in lipid digestion in the adult. Pancreatic lipases will be discussed first. Pancreatic lipases are secreted by the pancreas in their active forms. There is a second protein that is secreted by the pancreas in conjunction with lipase. This is a protein co-factor required for optimal enzyme activity of pancreatic lipase, facilitating binding of the pancreatic lipases at the lipid water interface. It is called colipase. Colipase is secreted in an inactive form and is activated in the duodenum by trypsin. Lipases are water soluble enzymes that catalyze the hydrolysis (breakdown) of water insoluble lipid substrates (made possible by the bile salt interactions forming micelles as described above). Lipase acts to convert triglycerides to a monoglyceride and two fatty acids. The sequence is as follows: Bile Salts (mechanical digestion) digestion) l Lipase (chemical l Fatty acids Large fat droplets -------------------------small fat droplets-------------------monoglycerides glycerol [1]. A pancreas produced lipase called phospholipase hydrolyzes phospholipids into a glycerolphospholipid + two free fatty acids. Another lipase called glycerolphospholipase separates the remaining molecule of glycerolphospholipid into glycerol and a fatty acid. These products then are able to be absorbed by the small intestines. 3 Cholesterol also is included in the micelles where a lipase called cholesterol esterase removes a fatty acid from the cholesterol molecule, thus making both available for absorption. Lipases are also produced by the salivary glands of the tongue and by the stomach, lingual and gastric lipase respectively. There are several differences from the pancreatic lipases in addition to their sites of production. These lipases are functional at lower pH than the pancreatic amylases that function in the basic environment of the duodenum. Gastric lipase works optimally at a pH of 3 to 6 [2], and lingual lipase at 4.5 to 5.4 [3]. Neither require colipase or bile salts to function As much as 20% of fat digestion can occur as a result the actions of gastric and lingual lipases, with the majority of this activity being the result of gastric lipase [2]. These acid lipases, however, are much less efficient than the pancreatic lipases. They only separate one fatty acid from the triglyceride. The free fatty acid is absorbable, but the residual diglyceride is not The production of pancreatic lipase is age related. Pancreatic response to hormonal secretory stimulation is absent or minimal at birth up to about age six months. After six months the response increases and is normal by age two [4,5]. Bile salt is also deficient in newborns. Breast milk does contain lipase and bile salts which accounts for 2/3 of the lipid hydrolysis in the newborn [15]. Those who are weaned early do not have the advantage of breast milk digestion of lipids, losing a significant amount of the lipid derived products necessary for cell wall structure, tissue development, and specifically brain growth and development. The lingual and gastric lipases are present at birth. Although this digestion of lipase is not as efficient as the pancreatic lipases, it does provide some lipid digestive products for absorption and utilization. In infants, these lipases provide up to 50% of lipolytic activity [2]. As a result, the absorptive rate of dietary fat by young infants can be as low as 65 % of that of the adult [3]. With malnutrition, all of the pancreatic enzyme activity is reduced, including lipase [7]. The size of the pancreas significantly 4 decreases in conjunction with the decrease in enzyme production [8]. In addition, the lining of the small intestines flattens and the mucosa is hypoplastic (reduced cellular production). This results in malabsorption due to increased amounts of sugar and fat remaining in the intestinal lumen. This, then, secondarily results in bile salt loss which compounds the effects of malabsorption and the resulting diarrhea [9]. Correction of malnutrition results in the pancreas and the small intestines returning to a normal state. This takes a few weeks [8]. In cases of pancreatic insufficiency other than as a result of malnutrition, the lingual and gastric lipases help compensate for pancreatic lipase deficit. The reason for decrease production of pancreatic enzymes in malnutrition is due to the inability to manufacture protein. Protein is actually broken down for energy production. This, no doubt, affects the enzyme (protein) production by the tongue and stomach as well as by the pancreas. Lipase is an active enzyme in barley malt. It is reasonably heat stable, surviving mashing [11,12]. Kilning, which has a peak temperature of 70 degrees centigrade, results a reduced lipase activity by about 10%. The optimal pH range of activity is between 4.0 and 5.0 [14], making it suitable for pre-digestion of the starchbased foods commonly used in the developing world. Because of this, the use of barley malt flour to predigest the common porridges and gruels of the developing world will provide essential products of lipid digestion for absorption by the intestines of weanlings, young infants and malnourished people of all ages that otherwise would not be made available to them. It is of note that it became obvious to those conducting the double blind study utilizing PowerFlour in Panama which children were receiving barley malt enhanced food. They were the ones whose diarrhea quickly resolved. This occurrence was most likely due to the fact that the pre-digested carbohydrate, protein and lipids were able to be absorbed , and, thus, removed from the gastrointestinal tract. The carbohydrate, protein and lipid in the 5 non-treated group remains in the gastrointestinal tract, resulting in the diarrhea commonly seen with malabsorption. BIBLIOGRAPHY 1 – Class Notes on Digestion – Accessed at http://www.stout.edu/faculty/millerlou/CLASS%@)%@)DIGESTION.htm on 11/11/2008 2 – Gastric Lipase – Accessed at http://en.wikipedia.org/wiki/gastric_lipase on 11/11/2008 3 – Lingual Lipase – Accessed at http://en.wikipedia.org/wiki/lingual_lipase on 11/11/2008 4 – Development of Functional Response in Human Exocrine Pancreas, Emanuel Lebenthal MD and P. C. Lee PhD, Pediatrics Vol. 66, No. 4, October 1980, pp556-560 5 – Serum Levels of Immunoreactive Trypsin during Development: Comparison with levels of Lipase and Amylase, Colombo C., Malavacca R, Ronchi M, Bottani P., Stripparo L, Corbetta C, and Sereni LP, Pediatric Gastroenterology Nutrition Vol. 9, No. 2, August 1989, pp 194-9 6 6 – Rudolf’s Pediatrics – David Celin – p 1312 accessed at http://books.google.com/books?id=0J6G3E1Y0EwC&pg= PA1312&1pg=PA1312&dq=b on 11/19/2008 7 – First Principles of Gastroenterology, Chapter 2/4Effects of Malnutrition on the Gastrointestinal Tract and Pancreas, pp60-1 Accessed at http://www.gastroresource.com/gitextbook/En/Chapter2/24.htm on 11/11/08 8 – Pancreatic size in Protein Energy Malnutrition: a Predictor of Nutritional Recovery, El-Hodhod M. A., Nassar M. F., Hetta O. A., and Gomaa S. M., European Journal of Clinical Nutrition, Vol. 59, No. 4, pp 467 – 73 9 – Digestive and Absorptive Phase Anomalies with the Exocrine Pancreatic Insufficiency of Cystic Fibrosis, Claude C. Roy, Andree M. Weber, Guy Lepage, Lesley Smith, and Emile Levy, Journal of Pediatric Gastroenterology and Nutrition, Vol. 7, Suppl. 1, November 1988, pp1-7 10 – Saliva and Gastrointestinal Functions of Taste, Mastication, Swallowing and Digestion, Oral Diseases, Vol. 8, No., published on line on 3May2002, pp117-29 11 – Activity of Lipase During Mashing, Paul Schwartz, Patriciz Stanley, and Sean Solberg, Journal of the American Society of Brewing Chemists, Vol. 60, No. 3, 2002, pp 107-09 12 – Activity of Lipase during Malting and Mashing – ASBC 2001 Meeting Abstract, p 13, Accessed at http://www.asbcnet.org/meetings/2001/Abstracts/P-13.htm on 11/17/2008 7 13 – Grain: Composition and Functionality – Chad Stevens, Quality Ale and Fermentation Fraternity, San Diego, CA, Accessed at www.quaff.org/SpeakerNotes/Grain_composition_Functio nality-Chad-Stevens.pdf on 11/17/2008 14 – Introduction to Enzymes: Effects of pH – Accessed at http://www.worthingtonbiochem.com/introbiochem/effectpH.html on 12/10/2008 15 – Current Pediatric Diagnosis and Treatment – William W. Hay, Anthony Hayward, Myron J. Levin, and Judith M. Sondheimer, pp 280 – 81, Accessed at http://books.google.com/books?id=hoa4CnJdQ1C&pg=PA280&1pg=PA280&dq=bile+sa on 11/19/2008 8