All Sphingolipids Are Formed From Ceramide

Ceramide is synthesized in the endoplasmic reticulum from the amino acid serine according to Figure 24-7. Ceramide is an important signaling molecule (second messenger) regulating pathways including apoptosis (processes leading to cell death), cell senescence, and differentiation, and opposes some of the actions of di-acylglycerol.

Sphingomyelins (Figure 14-11) are phospholipids and are formed when ceramide reacts with phos-phatidylcholine to form sphingomyelin plus diacylglyc-erol (Figure 24-8A). This occurs mainly in the Golgi apparatus and to a lesser extent in the plasma membrane.

Glycosphingolipids Are a Combination of Ceramide With One or More Sugar Residues

The simplest glycosphingolipids (cerebrosides) are galactosylceramide (GalCer) and glucosylceramide (GlcCer). GalCer is a major lipid of myelin, whereas GlcCer is the major glycosphingolipid of extraneural tissues and a precursor of most of the more complex glycosphingolipids. Galactosylceramide (Figure 24-8B) is formed in a reaction between ceramide and UDPGal (formed by epimerization from UDPGlc—Figure 20-6). Sulfogalactosylceramide and other sulfolipids such as the sulfo(galacto)-glycerolipids and the steroid sulfates are formed after further reactions involving 3'-phosphoadenosine-5'-phosphosulfate (PAPS; "active sulfate"). Gangliosides are synthesized from ceramide by the stepwise addition of activated sugars (eg, UDPGlc and UDPGal) and a sialic acid, usually N-acetylneuraminic acid (Figure 24-9). A large number of gangliosides of increasing molecular weight may be formed. Most of the enzymes transferring sugars from

+NH3

Pyridoxal phosphate, Mn2+ /

Pyridoxal phosphate, Mn2+ /

CH3 — (CH2)i2 — CH2—CH2—C — CH — CH2 — OH

NH3+

CH3 — (CH2)i2 — CH2—CH2—C — CH — CH2 — OH

NH3+

3-Ketosphinganine

3-KETOSPHINGANINE REDUCTASE

NADP+

CH3(CH2)12— CH2— CH2— CH — CH — CH2— OH I I OH NH3+

Dihydrosphingosine (sphinganine)

DIHYDROSPHINGOSINE N-ACYLTRANSFERASE

CH3 —(CH2)12 —CH2 — CH2 — CH — CH — CH2 — OH I I

OH NH CO R

Dihydroceramide

DIHYDROCERAMIDE DESATURASE

CH3— (CH2)12— CH = CH — CH — CH — CH2— OH I I

OH NH CO R

Ceramide

Figure 24-7. Biosynthesis of ceramide.

nucleotide sugars (glycosyl transferases) are found in the Golgi apparatus.

Glycosphingolipids are constituents of the outer leaflet of plasma membranes and are important in cell adhesion and cell recognition. Some are antigens, eg, ABO blood group substances. Certain gangliosides function as receptors for bacterial toxins (eg, for cholera toxin, which subsequently activates adenylyl cyclase).

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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