ME04 - Metabolism of Acylglycerols and Sphingolipids Flashcards
Major storage lipid in the adipose tissue
TRIACYLGLYCEROL
Major components of plasma and other membranes
PHOSPHOLIPIDS AND GLYCOSPHINGOLIPIDS
Lipid with a component of lung surfactant
Dipalmitoyl lecithin
Lipid which is a precursor of hormone second messenger
Inositol phospholipid
Lipid that is involved in inflammation and chemotaxis
Platelet activating factor
Lipid that is important in intercellular communication and contact, as receptors for bacterial toxins and as ABO blood group substance
Glycosphingolipid
CATABOLISM OF TAGs
Triacylglycerol»_space; (___Lipase)»_space;
Free fatty acids (Goes to the plasma bound to albumin > Tissue uptake > B-oxidation or reesterification ) + Glycerol (»_space; Glycerol kinase > Glycerol 3-phosphate > Reesterification )
Processes involved in the BIOSYNTHESIS
of TRIACYLGLYCEROL and PHOSPHOLIPIDS
ACTIVATION OF GLYCEROL
In the absence of glycerol kinase, glycerol 3-phosphate is derived from dihydroxyacetone phosphate (DHAP)
Dihydroxyacetone phosphate»_space; (Enzyme: Glycerol 3-phosphate Dehydrogenase)»_space; Glycerol 3- phosphate
Other products: NADH + H+ ; NAD+
ACTIVATION OF FATTY ACIDS
_ Involves hydrolysis of two high-energy bonds _ ENZYME: Acyl CoA Synthetase
SYNTHESIS OF TAG
DHAP > G3Phosphate > Monoacylglycerol 3Phosphate > Phosphatidic Acid > 1,2-Diacylglycerol > Triacylglycerol
What is the ALTERNATIVE PATHWAY OF TRIACYLGLYCEROL SYNTHESIS IN THE INTESTINAL MUCOSA
2-Monoacylglycerol»_space; 1,2-Diacylglycerol»_space; Triacylglycerol
Example of Phospholipids
Phosphatidylethanolamine
Phosphatidylserine
Phosphatidylcholine________
How does Phosphatidylethanolamine form Phosphatidylcholine
Phosphatidylethanolamine can undergo progressive methylation with SAM as methyl donor to form phosphatidylcholine
Synthesis of Cardiolipin
Phosphotidic acid»_space; CDP-Diacylglycerol > +Phosphatidylglycerol = Cardiolipin
WHAT IS THE ROLE OF PHOSPHATIDYLINOSITOL 4,5- BISPHOSPHATE IN HORMONE ACTION
Activator of protein kinase C
Effective releaser of Ca++ from intracellular storage
Major component of lung surfactant
DIPALMITOYL PHOSPHATIDYLCHOLINE
FUNCTION/EFFECT OF LUNG SURFACTANT
Lung surfactant reduces the surface tension of water (fluid) lining the surface of the alveolar sac, preventing collapse.
Without lung surfactant, sac collapses.
Ten times the normal pressure is needed for re-inflation.
Example of ETHER PHOSPHOLIPIDS
Plasmalogen and PAF
Phospholipid in the mitochondria
Plasmalogen
Function of PAF (Plasma-Activating Factor)
Aggregates platelets
Hypotensive
Ulcerogenic
Involved in inflammation, chemotaxis and protein phosphorylation
Where does the SYNTHESIS OF PLASMALOGEN AND PAF occur?
Occur in the peroxisomes
The common intermediate in the synthesis of triacylglycerol and glycerophospholipids
PHOSPHATIDATE
HOW ARE TRIACYLGLYCEROL AND PHOSPHOLIPID SYNTHESIS REGULATED?
Driven by availability of free fatty acids
Fatty acids that escapes oxidation are preferentially converted to phospholipids, and when this requirement is satisfied they are used for triacylglycerol synthesis
IN THE CATABOLISM OF PHOSPHOLIPIDS,
Different portions of the molecule turnover at different rates. True or False?
TRUE
Order of Phospholipases action sites
PLP A1, PLP A2, PLP C, PLP D
Catalyze transfer of a fatty acid residue from position 2 of lecithin to cholesterol to from cholesteryl ester
Responsible for cholesteryl esters in plasma lipoproteins
LECITHIN:CHOLESTEROL ACYLTRANSFERASE (LCAT)
Lecithin + CHOL»_space; (LCAT)»_space; Lysolecithin + Cholesteryl ester
Parent compound of all sphingolipids
Ceramide
Function of Ceramide
An important signaling molecule regulating pathways including programmed cell death (apoptosis), the cell cycle, and cell differentiation and senescence
Where is Ceramide synthesized?
In the endoplasmic reticulum from serine and palmitoyl CoA
Backbone of Ceramide are
Serine, Palmitoyl CoA and Fatty Acid
Present in plasma membranes; especially prominent in myelin, a membranous sheath that surrounds and insulates the axons of some neurons
SPHINGOMYELIN
How do you form Sphingomyelin from Ceramide?
Ceramide»_space; (Phosphatidylcholine>Diacylglycerol)»_space; Sphingomyelin
Include cerebrosides and gangliosides
Constituents of outer leaflet of the plasma membrane
Glycosphingolipid
C24 fatty acids that make up Glycosphingolipids
lignoceric acid cerebronic acid nervonic acid
Function of Glycosphingolipids
Important in intracellular communication and contact, as antigens such as ABO blood groups and as receptors for bacterial toxins
SYNTHESIS OF CEREBROSIDES AND THEIR SULFO DERIVATIVES
Ceramide»_space; (UDP-Gal > UDP)»_space; Galactosylceramide
(Cerebroside)»_space; (PAPS)»_space; Sulfogalactosylceramide
(Sulfatide)
CATABOLISM OF SPHINGOLIPIDS
Degraded within the lysosomes of phagocytic cells, particularly the histiocytes or macrophages of the RE system in the liver, spleen and bone marrows
Involves stepwise removal of each sugar and other components catalyzed by enzymes (specifically hydrolases) that cleaves specific bonds
Demyelinating disease
Involves the loss of both phospholipids and sphingolipids from white matter
Leads to slowing and eventual cessation of nerve impulse transmission
MULTIPLE SCLEROSIS
Manifest as weakness, lack of coordination, speech and vision problems
Due to absence of enzymes that degrade glycosphingolipids in the lysosomes
Rate of synthesis of stored lipids is normal
Complex lipids containing ceramide accumulate in cells, particularly neurons, causing neurodegeneration and shortening of life span
SPHINGOLIPID STORAGE DISEASES
Deficiency in Hexosaminidase A
Accumulating GM2 ganglioside
Rapidly progressing mental retardation, blindness, early mortality
Tay-Sachs Disease
Deficiency in Hexosaminidase B
Accumulating Globoside, GM2 ganglioside
Same symptoms as Tay-Sachs, progresses more rapidly
Sandhoff-Jatzkewitz disease
Deficiency in GM2 activator (GM2A)
GM2 ganglioside
Tay-Sachs AB variant
Deficiency in Glucocerebrosidase
Accumulating Glucocerebroside
Hepatosplenomegaly, mental retardation in nfantile form, long bone degeneration
Gaucher disease
Deficiency in a-Galactosidase A
Accumulating Globotriaosylceramide also called ceramide
trihexoside (CTH)
Kidney failure, skin rashes
Fabry disease
Deficiency in Sphingomyelinase
Niemann-Pick Disease
Deficiency in Galactocerebrosidase
Accumulating Galactocerebroside
Mental retardation, myelin deficiency
Krabbe disease; globoid leukodystrophy
Deficiency in Arylsulfatase A
Sulfatide
Mental retardation, metachromasia of nerves
Sulfatide lipodosis; metachromatic leukodystrophy
Deficiency in a-L-Fucosidase
Accumulating Pentahexosylfucoglycolipid
Cerebral degeneration, thickened skin, muscle spasticity
Fucosidosis
Deficiency in Acid ceramidase
Accumulating Ceramide
Hepatosplenomegaly, painful swollen joints
Farber lipogranulomatosis
