Anatomy And Physiology

Anatomy Physiology



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Fat or its derivatives are generally considered water insoluble and human blood is a medium, which generally favors water-soluble particles. When a person eats a fat rich diet, the nutrients absorbed in the gut, which largely contain fats, have to be transported via the blood circulation to organs and tissues waiting to receive such nutrients. However, the water insoluble nature of fats makes it impossible for such a nutrient to enter the circulation by itself. Thus, an intermediary an agent is required to settle the differences in solubility and transport of such lipid particles and in humans; this agent is given the name chylomicrons.

What is the structure of chylomicrons?

Chylomicrons are considered large lipoproteins because of lipid, phospholipid and protein constituents. However, the protein constituents are extremely low although their role in the chylomicrons metabolism remains vital. In general, the chylomicrons consist of over 80% triglycerides, about 9% phospholipids and around 6% cholesterols or cholesterol-esters. According to scientists, the diameter of these particles can range from 75 to 1200 nm and it would be largest at its production in the intestinal cells. During its life cycle, the constituency of chylomicrons will change and some of the protein in the form of apolipoprotein will enter the chylomicron particles as it reaches its destination via the circulation.

Where does chylomicrons originate?

Chylomicrons originate in the absorptive cells of the intestine, which are called the intestinal epithelial cells or enterocytes. These cells are largely located in the duodenum of the small intestine and are highly efficient in absorbing and transporting the absorbed nutrients through the circulation or else through the lymphatic system. In the case of chylomicrons, once formed, the large size prevents them from entering the circulation directly and they would therefore be transported through the lymphatic system until reaching the circulation.

What does chylomicrons do?

As mentioned above, chylomicrons will form a particle consisting of triglycerides and cholesterol core with a surface consisted of apolipoprotein and phospholipids. This unique structure will allow fatty nutrients to enter the human circulation following its absorption in the intestinal cells. Furthermore, the chylomicrons will be able to gather certain elements including proteins and cholesterols as they travel through the lymphatic system and the circulation. Once the chylomicron reaches a tissue, which requires or allows its metabolism, it will free-up the triglycerides and cholesterols and would leave the tissues back into the circulation. Thus, chylomicrons play an essential role in the lipid metabolism.

What is the life cycle of chylomicrons?

The life cycle of chylomicrons can be illustrated as having three distinct stages. These stages include, the nascent chylomicrons, the mature chylomicrons and the remnant chylomicrons.

Nascent chylomicrons:

This is the initial form of the chylomicrons, which are formed in the intestinal epithelial cells or inside the enterocytes. It is formed by combining triglycerides, phospholipids, cholesterol esters and an apolipoprotein known as apolipoprotein (apo) B48. Once formed, the particles are secreted into the lymphatic system (and hence the name ‘chyle’) before being carried into the circulation at the site where the major lymphatic vessel (thoracic duct) enters the subclavian vessel.

The nascent chylomicrons would further receive cholesterol particles from other apolipoproteins present in the lymph or else in the plasma. At the same time, it would receive an apolipoprotein known as ‘apo C’ from high-density lipoproteins (HDL) which will convert nascent chylomicrons into its mature forms.

Mature chylomicrons:

Following receiving apo Cs from HDL (more specifically apolipoprotein C-II) the chylomicrons will have the ability to undergo metabolism at the sites where lipoprotein lipase enzyme activity is abundant. Such sites include skeletal muscles, cardiac muscles, adipose tissues, and mammary glands. One common characteristic of all these tissues is that their high requirement for triglycerides for various needs such as energy, storage or else production of milk.

Remnant chylomicrons:

When mature chylomicrons encounter the enzyme lipoprotein lipase, they will break down the triglycerides into fatty acids and monoglycerides. This will make the large triglyceride core of the chylomicrons to shrink and thus become a triglyceride depleted, cholesterol rich, and protein rich, ‘remnant chylomicrons’.

The remnant chylomicrons will exchange the excess apolipoproteins, specifically the apo Cs, with HDL and thereby return apo Cs for re-use. The remaining chylomicron particle would be metabolized in the liver via the LDL receptors and it will be aided by the presence of apo E that it received from various tissues where chylomicrons were metabolized. The clearing up process of remnant chylomicrons takes place within few hours of ingesting fatty diets and therefore is an extremely efficient system in healthy individuals. However, in some individuals, the duration for clearing up may not be so rapid and thereby would contribute to prolonged elevation of triglycerides following a meal.

Reference:

Lectures in clinical atherosclerosis and dyslipidemia : http://www.cmglinks.com/asa/lectures/Part_2/lecture/2.htm

Herz J. Low-density lipoprotein receptor-related protein. In: Lipoproteins in Health and Disease. Edited by DJ Betteridge, DR Illingworth and J Shepherd. London: Arnold, 1999;333-359.

M Mahmood Hussain: "Review Article: A proposed model for the assembly of chylomicrons"; Arterosclerosis; Vol. 148; 2000; pages 1-15;


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