Biochemistry: Lipids: Sphingolipid Metabolism (PDF)

1A BIOCHEMISTRY LIPIDS: SPHINGOLIPID METABOLISM DR. B. JANDOC OUTLINE...

1A BIOCHEMISTRY LIPIDS: SPHINGOLIPID METABOLISM DR. B. JANDOC OUTLINE  functions: I. Overview o Intercellular communication A. Ceramide o Antigenic determinants of ABO blood group B. Sphingosine o Some are used as receptors by viruses and bacterial toxins II. Sphingolipids A. Sphingophospholipids: Sphingomyelin A. SPHINGOPHOSPHOLIPIDS B. Glycosphingolipids 1. Neutral glycopshingolipids 2. Acidic glycosphingolipids III. Clinical Application  Backbone: sphingosine A. Multiple sceloris  long chain fatty acid is B. Sphingolipidoses attached to the amino group via an C. Case: Gaucher’s Disease amide linkage LEGENDS: - from books - from Dr. Jandoc’s lecture SPHINGOMYELIN  Produced from esterification of the alcohol group at carbon 1 of LIPIDS: SPHINGOLIPID METABOLISM sphingosine to phosphorylcholine  Only sphingolipid that contain phosphate and has no sugar moiety I. OVERVIEW  Formed from ceramide (fatty acid + sphingosine), cytidine diphosphate (CDP) , and choline  The only significant sphingophospholipid in humans  Major phospholipid components of membranes in neural tissues  Important constituent of the myelin in nerve fibers  Hydrolysis will yield: o Fatty acid o Phosphoric acid o Choline o Sphingosine A. CERAMIDE Functions  synthesized in the endoplasmic reticulum from the amino 1. Major structural lipid in nerve tissue membranes acid serine 2. Insulates and protects neuronal fibers of the CNS through a layered membranous structure → myelin sheath  serine + palmitoyl CoA condense → forms a reduced product → addition of a very-long-chain fatty acid (22-carbon containing)  Myelin sheath – contains longer chain fatty acids: o Lignoceric acid forms an amide with the amino (NH2) group → formation of o Nervonic acid double bond  Oxidation of palmitoyl moiety by FAD  Grey matter of the brain – contains stearic acid 3. Ceramide with a fatty acid 30 carbons long  Serve as precursor of glycolipids  Major component of skin B. SPHINGOSINE  Regulates skin’s water permeability  Common precursor of sphingolipids Synthesis  Amino alcohol with 2 asymmetric carbon atoms (carbons 2 and 1. Fatty acid is attached to the amino group of sphingosine by 3) an amide linkage → ceramide (can also serve as precursor  D-erythro form – naturally occurring sphingosine of glycolipids)  Backbone of sphingolipids  Frequently found fatty acids:  Synthesized from serine and palmitoyl CoA by a 2-step process that requires NADPH o Palmitic acid ( most common) o Stearic acid II. SPHINGOLIPIDS o Lignoceric acid  Present in nearly all human tissues o Nervonic acid  Greatest concentration in the CNS (white matter) 2. Alcohol group at carbon 1 of sphingosine is esterified to  All are derived from sphingosine phosphorylcholine → sphingomyelin Trans Finals 4 | ABACCO, ALDERITE, ASISTIN, BALANZA, BAYAS, BIANG 1 of 5  1A BIOCHEMISTRY LIPIDS: SPHINGOLIPID METABOLISM DR. B. JANDOC 3. Palmitoyl CoA losses CoA and reacts with ß-aminoalcohol 2. Type B derived from serine (requires coenzyme pyridoxal  >5% enzymatic acitivity phosphate) → product reduced to sphingosine → acylated  Little to no damage to neural tissue at the amino group → ceramide reacts with CDP-choline  life expectancy: early adulthood → sphingomyelin  affects lungs, spleen, liver, and bone marrow Degradation B. GLYCOSPHINGOLIPIDS  Sphingomyelinase o Lysosomal enzyme  essential in all o Hydrolyzes membranes of the body – greatest in sphingomyelin nerve tissues removing  Almost all glycolipids are phosphorylcholine derivatives of ceramide (molecule of – leaving ceramide fatty acid is attached to the amino o Type of alcohol sphingosine) phospholipase C  Contains both lipid and carbohydrate  Ceramidase o Cleaves ceramide  Carbohydrate portion → sphingosine + free fatty acid o exposed in the aqueous environment of the cell  Ceramide – membrane role as o Serve as cell surface receptors for cholera toxin, tetanus intracellular toxin, and certain viruses and microbes messenger o Antigenic determinant – source of:  Sphingosine – role as intracellular messenger; inhibits  blood group antigens protein kinase C  various embryonic antigens  Ceramide and sphingosine may also promote  tumor antigens apoptosis and for regulation of signal transduction  Location: primarily in the outer layer of the plasma membrane pathways → interact with extracellular environment → regulation of cellular interactions, growth, and development Niemann-Pick Disease  Autosomal recessive disease Structure  Inability to degrade sphingomyelin due to sphingomyelinase  Differences from sphingomyelin: deficiency o Do not contain phosphate o Polar head function is provided by a monosaccharide or 1. Type A oligosaccharide attached directly to the ceramide by an O- glycosidic bond 