Chylomicrons are assembled in the intestinal mucosa…. HOW?

Chylomicrons are assembled in the intestinal mucosa as a means to transport dietary cholesterol and triacylglycerols to the rest of the body. Chylomicrons are, therefore, the molecules formed to mobilize dietary (exogenous) lipids. The predominant lipids of chylomicrons are triacylglycerols (see Table above). The apolipoproteins that predominate before the chylomicrons enter the circulation include apoB-48 and apoA-I, -A-II and IV. ApoB-48 combines only with chylomicrons.

Chylomicrons leave the intestine via the lymphatic system and enter the circulation at the left subclavian vein. In the bloodstream, chylomicrons acquire apoC-II and apoE from plasma HDLs. In the capillaries of adipose tissue and muscle, the fatty acids of chylomicrons are removed from the triacylglycerols by the action of lipoprotein lipase (LPL), which is found on the surface of the endothelial cells of the capillaries. The apoC-II in the chylomicrons activates LPL in the presence of phospholipid. The free fatty acids are then absorbed by the tissues and the glycerol backbone of the triacylglycerols is returned, via the blood, to the liver and kidneys. Glycerol is converted to the glycolytic intermediate dihydroxyacetone phosphate (DHAP). During the removal of fatty acids, a substantial portion of phospholipid, apoA and apoC is transferred to HDLs. The loss of apoC-II prevents LPL from further degrading the chylomicron remnants.

Chylomicron remnants, containing primarily cholesteryl esters, apoE and apoB-48, are then delivered to, and taken up by, the liver through interaction with the LDL receptor which requires apoE or via the chylomicron remnant receptor, which is a member of the LDL receptor-related protein (LRP) family. The recognition of chylomicron remnants by the hepatic remnant receptor also requires apoE. Chylomicrons function to deliver dietary triacylglycerols to adipose tissue and muscle and dietary cholesterol to the liver.

How the lipids absorbed in intestine ?

In order for the body to make use of dietary lipids, they must first be absorbed from the small intestine. Since these molecules are oils, they are essentially insoluble in the aqueous environment of the intestine. The solubilization (or emulsification) of dietary lipids is therefore accomplished by means of bile salts, which are synthesized from cholesterol in the liver and then stored in the gallbladder; they are secreted following the ingestion of fat.

The emulsification of dietary fats renders them accessible to pancreatic lipases (primarily lipase and phospholipase A₂; PLA₂). These enzymes, secreted into the intestine from the pancreas, generate free fatty acids and a mixtures of mono- and diacylglycerols from dietary triacylglycerols. Pancreatic lipase degrades triacylglycerols at the 1 and 3 positions sequentially to generate 1,2-diacylglycerols and 2-acylglycerols. Phospholipids are degraded at the 2 position by pancreatic PLA₂ releasing a free fatty acid and the lysophospholipid. The products of pancreatic lipases then diffuse into the intestinal epithelial cells, where the re-synthesis of triacyglycerols occurs.

Dietary triacylglycerols and cholesterol, as well as triacylglycerols and cholesterol synthesized by the liver, are solubilized in lipid-protein complexes. These complexes contain triacylglycerol lipid droplets and cholesteryl esters surrounded by the polar phospholipids and proteins identified as apolipoproteins. These lipid-protein complexes vary in their content of lipid and protein.

Theories Contributing to Modern Biology

Modern biology is based on several great ideas, or theories:

• The Cell Theory
• The Theory of Evolution by Natural Selection
• Gene Theory
• Homeostasis

Robert Hooke (1635-1703), one of the first scientists to use a microscope to examine pond water, cork and other things, referred to the cavities he saw in cork as "cells", Latin for chambers. Mattias Schleiden (in 1838) concluded all plant tissues consisted of cells. In 1839, Theodore Schwann came to a similar conclusion for animal tissues. Rudolf Virchow, in 1858, combined the two ideas and added that all cells come from pre-existing cells, formulating the Cell Theory. Thus there is a chain-of-existence extending from your cells back to the earliest cells, over 3.5 billion years ago. The cell theory states that all organisms are composed of one or more cells, and that those cells have arisen from pre-existing cells.

Figure : James Watson (L) and Francis Crick (R), and the model they built of the structure of deoxyribonucleic acid, DNA. While a model may seem a small thing, their development of the DNA model fostered increased understanding of how genes work. Image from the Internet.

In 1953, American scientist James Watson and British scientist Francis Crick developed the model for deoxyribonucleic acid (DNA), a chemical that had (then) recently been deduced to be the physical carrier of inheritance. Crick hypothesized the mechanism for DNA replication and further linked DNA to proteins, an idea since referred to as the central dogma. Information from DNA "language" is converted into RNA (ribonucleic acid) "language" and then to the "language" of proteins. The central dogma explains the influence of heredity (DNA) on the organism (proteins).

Homeostasis is the maintenance of a dynamic range of conditions within which the organism can function. Temperature, pH, and energy are major components of this concept. Thermodynamics is a field of study that covers the laws governing energy transfers, and thus the basis for life on earth. Two major laws are known: the conservation of matter and energy, and entropy. These will be discussed in more detail in a later chapter. The universe is composed of two things: matter (atoms, etc.) and energy.

These first three theories are very accepted by scientists and the general public. The theory of evolution is well accepted by scientists and most of the general public. However, it remains a lightening rod for school boards, politicians, and television preachers. Much of this confusion results from what the theory says and what it does not say.