Triacylglycarois and structure of it,yes

Structure
Composition
Enzymes
Function
Disorders

1. Triacylglycerols

2. Structure of triacylglycerol (TAG) Mono-, di-, and triacylglycerols consist of one, two, or three molecules of fatty acid esterified to a molecule of glycerol. Fatty acids are esterified through their carboxyl groups, resulting in a loss of negative charge and formation of “neutral fat.” The three fatty acids esterified to a glycerol molecule are usually not of the same type. The fatty acid on carbon 1 is typically saturated, that on carbon 2 is typically unsaturated, and that on carbon 3 can be either. Recall that the presence of the unsaturated fatty acid(s) decrease(s) the melting temperature (Tm) of the lipid Because TAGs are only slightly soluble in water and cannot form stable micelles by themselves, they coalesce within adipocytes to form oily droplets that are nearly anhydrous. These cytosolic lipid droplets are the major energy reserve of the body

3. Synthesis of glycerol phosphate Glycerol phosphate is the initial acceptor of fatty acids during TAG synthesis. There are two pathways for glycerol phosphate production In both liver (the primary site of TAG synthesis) and adipose tissue, glycerol phosphate can be produced from glucose, using first the reactions of the glycolytic pathway to produce dihydroxyacetone phosphate Next, DHAP is reduced by glycerol phosphate dehydrogenase to glycerol phosphate. A second pathway found in the liver, but not in adipose tissue, uses glycerol kinase to convert free glycerol to glycerol phosphate

4. Synthesis of a molecule of TAG from glycerol phosphate and fatty acyl CoA: These include the sequential addition of two fatty acids from fatty acyl CoA, the removal of phosphate, and the addition of the third fatty acid.

5. OVERVIEW OF GLYCOLIPIDS Glycolipids are molecules that contain both carbohydrate and lipid components. Like the phospholipid sphingomyelin, glycolipids are derivatives of ceramides in which a long-chain fatty acid is attached to the amino alcohol sphingosine. They are, therefore, more precisely called glycosphingolipids Like the phospholipids, glycosphingolipids are essential components of all membranes in the body, but they are found in greatest amounts in nerve tissue. They are located in the outer leaflet of the plasma membrane, where they interact with the extracellular environment. As such, they play a role in the regulation of cellular interactions, growth, and development. Glycosphingo lipids are antigenic, and they have been identified as a source of blood group antigens, various embryonic antigens specific for particular stages of fetal development, and some tumor antigens. They also serve as cell surface receptors for cholera and tetanus toxins, as well as for certain viruses and microbes. Genetic disorders associated with an inability to properly degrade the glycosphingolipids result in lysosomal accumulation of these compounds.

6. STRUCTURE OF GLYCOSPHINGOLIPIDS The glycosphingolipids differ from sphingomyelin in that they do not contain phosphate, and the polar head function is provided by a monosaccharide or oligosaccharide attached directly to the ceramide by an O-glycosidic bond The number and type of carbohydrate moieties present help determine the type of glycosphingolipid. Neutral glycosphingolipids The simplest neutral (uncharged) glycosphingolipids are the cerebrosides. These are ceramide monosaccharides that contain either a molecule of galactose ( galactocerebroside —the most common cerebroside found in membranes,) or glucose (glucocerebroside, which serves primarily as an intermediate in the synthesis and degradation of the more complex glycosphingolipids). As their name implies, cerebrosides are found predominantly in the brain and peripheral nervous tissue, with high concentrations in the myelin sheath. Ceramide oligo - saccharides (or globosides ) are produced by attaching additional monosaccharides (including GalNAc) to a glucocerebroside. Examples of these compounds include: Cerebroside (glucocerebroside): Cer-Glc Globoside ( lactosylceramide ): Cer - Glc -Gal Globoside (Forssman antigen): Cer - Glc -Gal-Gal- GalNac - GalNac (Cer = ceramide, Glc = glucose, Gal = galactose, GalNac = N- acetylgalactosamine )

7. Acidic glycosphingolipids Acidic glycosphingolipids are negatively charged at physiologic pH. The negative charge is provided by N-acetylneuraminic acid (NANA, a sialic acid, in gangliosides, or by sulfate groups in sulfatides. 1. Gangliosides: These are the most complex glycosphingolipids, and are found primarily in the ganglion cells of the central nervous system, particularly at the nerve endings. They are derivatives of ceramide oligosaccharides, and contain one or more molecules of NANA. The notation for these compounds is G (for ganglioside) plus a subscript M, D, T, or Q to indicate whether there is one (mono), two (di), three (tri), or four ( quatro ) molecules of NANA in the ganglioside, respectively. Additional numbers and letters in the subscript designate the monomeric sequence of the carbohydrate attached to the ceramide. Gangliosides are of medical interest because several lipid storage disorders involve the accumulation of NANA-containing glycosphingolipids in cells 2. Sulfatides: Sulfoglycosphingolipids (sulfatides) are cerebrosides that contain sulfated galactosyl residues, and are therefore negatively charged at physiologic pH. Sulfatides are found predominantly in nerve tissue and kidney.,

8. SYNTHESIS AND DEGRADATION OF GLYCOSPHINGOLIPIDS Synthesis of glycosphingolipids occurs primarily in the Golgi by sequential addition of glycosyl monomers transferred from UDP–sugar donors to the acceptor molecule. A. Enzymes involved in synthesis The enzymes involved in the synthesis of glycosphingolipids are glycosyl transferases, each specific for a particular sugar nucleotide and acceptor. B. Addition of sulfate groups A sulfate group from the sulfate carrier, 3'-phosphoadenosine-5’- phosphosulfate , is added by a sulfo transferase to the 3'-hydroxyl group of the galactose in a galactocerebroside . Galac to cerebroside 3-sulfate is the major sulfatide in the brain

9. Degradation of glycosphingolipids Glycosphingolipids are internalized by endocytosis as described for the glycosaminoglycans. All of the enzymes required for the degradative process are present in lysosomes, which fuse with the endocytotic vesicles. The lysosomal enzymes hydrolytically and irreversibly cleave specific bonds in the glycosphingolipid. D egradation is a sequential process following the rule “last on, first off,” in which the last group added during synthesis is the first group removed in degradation Sphingolipidoses In a normal individual, synthesis and degradation of glycosphingolipids are balanced, so that the amount of these compounds present in membranes is constant. If a specific lysosomal hydrolase required for degradation is partially or totally missing, a sphingolipid accumulates . Lysosomal lipid storage diseases caused by these deficiencies are called sphingolipidoses. The result of a specific hydrolase deficiency may be seen dramatically in nerve tissue, where neurologic deterioration can lead to early death.

10. Common properties: A specific lysosomal hydrolytic enzyme is deficient in each disorder. Therefore, usually only a single sphingo lipid accumulates in the involved organs in each disease. The disorders are progressive and, although many are fatal in childhood, extensive phenotypic variability is seen leading to the designation of different clinical types Genetic variability is also seen because a given disorder can be caused by any one of a variety of mutations within a single gene. The sphingolipidoses are autosomal recessive diseases , except for Fabry disease, which is X-linked . The incidence of the sphingolipidoses is low in most populations, except for Gaucher and Tay-Sachs diseases, which, like Niemann-Pick disease, show a high frequency in the Ashkenazi Jewish population Diagnosis and treatment: A specific sphingolipidosis can be diagnosed by measuring enzyme activity in cultured fibroblasts or peripheral leukocytes, or by analysis of DNA Histologic examination of the affected tissue is also useful. Prenatal diagnosis, using cultured amniocytes or chorionic villi, is available.