Glycolipid metabolism

Introduction to glycolipids and their metabolism in the human

In the previous sections we discusses phospolipids, as well as other types of lipids. The glycolipids are yet another division of lipids that is utilised by the human as well as other forms of life. Glycolipids are named in reference to their chemical structure: practically all glycolipids are derivatives of ceramides. Ceremides are a fatty acid bonded or connected to the amino alcohol sphingosine. In fact, although the class of lipids we discussed called phospholipids, are chemically different from glycolipids, the phospholipid we call sphingomyelin, also is derived from ceramides. Glycolipids, however, are different as well, because they contain no phosphates in comparison to phospholipids. What also puts glycolipids in a class of their own is the fact that the fat is connected to a sugar molecule. Hence, the name glycolipid (glyco=sugar, lipid=fat). Therefore, glycolipids are simply fats that are bonded to sugars. So, since glycolipids are built from sphingosine, fat, and a sugar, we can be more exact in our naming and call them "glycosphingolipids".

A "free" fatty acid.

Functions of glycolipids

In common with the phospholipids, the glycolipids are an essential part of cell membranes. Glycolipids also help determine the blood group of an individual. In regards to blood grouping, glycolipids act as receptors at the surface of the red blood cell. This is important as we can use this principle to classify our blood type, which is critical during transfusions, etc. If we give the incorrect type of blood to an individual, the recipients immune system detects these differences and treats the donated blood cells as foreign, and can cause death. Glycolipids also play a "hormonal" funtion during embryonic development. In microorgansims, certain glycolipids even help ensure their survival by "tricking" our immune system into thinking they are not foreign. This helps them to evade immune survelllence. On the other hand, some viruses, bacteria (eg., cholera) use glycolipids on their cell surface as well. This helps the immune system destroy and clear the pathogen from the body.

Examining the illustration above, we can see that there are single bonds between each carbon in the tail. Although in each section of the tail, a 'zig-zag' pattern exists, overall, the tail has a straight appearance. If we were remove one of the single bonds between carbon atoms, and replace it with a double bond the molecule would no longer have an overall straight appearance as illustrated below.

A free fatty acid with multiple single bonds between carbon atoms and 1 single double bond between carbon atoms.

Types of glycolipids

Cerebrosides-Cerebroside (from cerebro=brain) are glycolipids that are found primarily in the brain and peripheral (other areas of the body) nervous tissue. Cerebrosides in the nervous tissue are found in the myelin sheath. The myelin sheath in the protective coating surrounding each nerve, and this coating acts as an insulator and aids in the proper conduction of a nervous impoulse. We can see how important this fatty coating is when we look at the disease process known as Multiple Sclerosis. There are different types of glycolipids, each characterised by the sugar that they are bonded to and the type of fatty acid that is used to bond to the sugar. Sugars such as galactose and glucose are bonded to the lipid. When a galactose or glucose molecule is bonded to the lipid, the glycolipid is called a galactocerebroside or glucocerebroside, respectively.

Ceramide oligosaccharides-Just as we discussed ceremides, another group of glycolipids is termed the ceremide oligosaccharides (ceremide="ceremide", oligo="short", saccharide="sugar"). Basically, these are ceremides with short chains of sugars, in comparison to cerebrosides with only "one" sugar attached. Examples are listed below.

Example ceramide oligosaccharides.
Globoside Forssman Antigen Ceramide trihexoside

Gangliosides-Above we discussed ceramides. These glycolipids (aka glycosphingolipids) are neutral (uncharged). The gangliosides on the other hand, are acidic in pH, and they are the more complex of the glycolipids. Basically, gangliosides are ceramide oligosaccharides (discussed above) with an extra substance attached. This substabce is called N-acetylneuraminic acid (abbreviated NANA), and it's this NANA that gives the glycolipid its negative charge and hence, acidic quality. Gangliosides are medically significant because some of these accumulate in an individual in certain genetically inherited diseases. For example, ganglioside GM 2, a ganglioside with several NANA groups attached, accumulates in the individual with Tay-Sachs disease. Tay-Sachs is but one of the several diseases in which a genetic lack or inefficiency of an enzyme needed to metabolize a glycolipid can cause catastrophic consequences. Hopefully, through genetic engineering, or suitable pharmacological (drug) therapy, we can find more helpful means to support anyone with these enzyme deficiencies.

Sulfoglycosphingolipids-These cerebrosides are also called sulfatides, They are simply cerebrosides with a sulfate residue on the sugar portion of glycolipid. This long name simply implies a cerebroside that contains a sulfated galactose. As you can see, galactosyl, contains the word "galact" meaning the sugar galactose. The difference here, is that the galactose has sulfate added to it, and this extra chemical group causes it to have a negative charge. Now that you know the chemical aspects, what does this have to do with our health? These are but one of the many types of lipids. However, this particular lipid is found primarily in the medulated nerve fibres and can accumulate in the white matter of the brain in metachromatic leukodystrophy.

Synthesis and degradation of glycolipids

Synthesis of glycolipids occurs with the help of enzymes that sequentially add sugars to the lipid. When the lipids are required to be broken down, enzymes in the lysosome of the cell help to remove the sugar subunits. This is important medically, because a deficiency of any of the enzymes involved in these processes cause an accumulation of a particular glycolipid that cannot be further broken down. When this accumulation occurs, the excess lipid remains trapped in the plasma or the cells and deposits in various organ/tissue systems and unfortunately, damages them.

Classes of lipids

Dietary lipid metabolism of Triacylglycerols

Dietary lipid metabolism of Phospholipids

Cholesterol and steroids

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