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fats
Lipid digestion, absorption and metabolism
nutrition


definition

Lipid digestion, absorption and metabolism
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overview:
• Lipid digestion begins in the mouth and stomach where ligual lipase and gastric lipase act to break down the triglycerides found in foods. These 2 enzymes are rather weak, however, and only a small amount of fat digestion occurs by the time fat reaches the small intestine. Primarily fat digestion occurs in the proximal small intestine through the action of bile salts released from the gall bladder in response to chyme reaching the duodenum. Without bile salts, as when the gall bladder has been removed, fat digestion is severely hampered. Bile salts (see diagram of emulsification of fats page 41) break down larger fat globules into tiny water soluble particles called micelles. Once formed, they can be broken down at the brush border of the intestines through the action of pancreatic lipase, which acts to cleave off fatty acids from the triglycerides found inside the micelles (see diagram page 41).

Once acted upon by pancreatic lipase, the micelles release free fatty acids, mono and diglycerides. The free fatty acids are carried across the intestinal epithelial cells and reformed back into chylomicrons whereupon they enter into the lacteals. From the lacteals they travel through the lymph system up to the thoracic duct, located in the upper area of the neck, where they enter into the general circulation. Small and medium chain length fatty acids, which have been cleaved from the micelles, can enter directly into the bloodstream because they are more water soluble. All blood from the intestines goes first to the liver before it enters into the general circulation.

The fatty acids can be utilized as fuel by virtually all tissues in the body except the brain, RBC’s, the skin, and the renal medulla. The muscles utilize fatty acids as a major a source of energy even when glucose is available. Glycerol gets oxidized by only a couple of tissues in the body. When fatty acids are used for energy it is under the control of hormone sensitive lipase, which is responsible for cleaving fatty acids and glycerol from fat cells. Free fatty acids are then carried into the circulation by albumin for transport to the liver. Glycerol diffuses back into the plasma because it can only be oxidized in the liver and kidney cells.

In the liver fatty acids are Beta oxidized, a process that cleaves fatty acids 2 carbons at a time. As oxidation proceeds, shorter fatty acids are formed with the final product being acetyl CoA. The rate limiting step in beta oxidation involves L-carnitine, an amino acid compound. This process yields energy enriched molecules which can be used for energy. Unoxidized fatty acids get stored throughout the body as subcutaneous fat which can later be accessed and used as an energy source when needed.

Glycerol in the liver is either incorporated back into triglycerides or converted into glucose to be used as an energy source.

» Ketone Bodies

Usually the liver produces more acetyl CoA than it can oxidize. The excess is condensed into two molecule units to form acetoacetic acid. This acetoacetic acid can diffuse from the liver into the circulation where it can be carried to the peripheral tissues to be converted into acetyl CoA and used for Beta oxidation. During periods of starvation, including very low carbohydrate diets, or in diabetes, the body relies mostly on fats for energy. Large quantities of fats from around the body get mobilized and transported to the liver where they are broken down into acetoacetic acid subunits. These subunits get converted into beta-hydroxybutyric acid and acetone. These 3 compounds are collectively known as ketone bodies. Skeletal muscle and the heart use these ketone bodies for producing energy. It is interesting that after several days of a low glucose availability, the brain starts using ketone bodies for its energy requirements and even prefers them over glucose.

The initial breakdown of the fatty acids into acetoacetic acid in the liver requires a supply of oxaloactic acid, which is generated primarily from carbohydrate metabolism. Once oxaloacetic acid is produced, it can combine with acetoacetic acid to make citric acid. Citric acid is the beginning substrate for the Kreb cycle. In severe carbohydrate restriction or starvation, not enough oxaloacetic acid is present to combine with acetoacetic acid. The result is that ketone bodies start to build up in the tissues. This causes ketones to appear in the urine (ketonuria) and to be excreted in the breathe (acetone smell in the breath).

Excessive ketones in the liver must be removed from the body. They must be carried into the blood and excreted in the urine in combination with a neutralizing base. The available base in the blood, sodium ions, becomes used up. This results in the depletion of body stores of alkalinizing fluids which causes an overall acidification of the blood called ketoacidosis. Ketoacidosis can cause a number of deleterious effects including excessive excretion of calcium and, if severe enough, death.

» Hormonal Regulation of Lipid Metabolism
• A number of hormones in the body have a significant regulatory action on lipid metabolism. Below is a list of a few active hormones:
Insulin increases lipogenesis and inhibits lipolysis (fat breakdown and metabolism) by fat tissues. It also decreases the activity of hormone sensitive lipase (HSL). HSL is responsible for the enzymatic breakdown of triglycerides into free fatty acids stored in fat tissues.
Thyroid hormones increase cellular metabolism (particularly T3) and increases fat mobilization from fat cells.
Glucocorticoids (ACTH and cortisol) increases the rate of fat mobilization by increasing the activity of HSL and increasing the permeability of the fat cell membranes to fatty acids.
Epinephrine, norepinephrine, adrenal (medulla hormones) increase the activity of HSL and, therefore, indirectly increase the rate of fat mobilization.
Growth hormone has pronounced lipolytic effects.


 

footnotes

Marz, Russell. Medical Nutrition From Marz. Second Edition. Portland, OR. 1997.