Flashcards in cholesterol and complex lipids Deck (19)
· Describe the sources of and fates of cholesterol.
sources: dietary (300-600g per day, half is absorbed and half is excreted in stool) and de novo synthesis (1g per day). Fates: cell membranes, precursor for steroid horomones, bile acids and vit D
location of cholesterol synthesis
Occurs in cytosol of liver mainly, but also adrenal cortex, the ovaries and the testes also synthesize cholesterol to make steroid hormones
what is the source of energy for cholesterol synthesis
· Describe in general the steps in the de novo synthesis of cholesterol
Acetyl CoA > HMG CoA > mevalonate (HMG CoA reductase) > geranyl pyrophosphate > farnesyl pyrophosphate > squalene > cholesterol
list 3 pathways that contribute to intracellular cholesterol content in hepatocytes
Synthesis, uptake of lipoprotein cholesterol from LDL, and enterohepatic circulation of bile acids.
· Identify the key regulated step in cholesterol synthesis and describe how this step is regulated
HMG CoA reductase is rate limiting step and key regulated step. Regulated by transcriptional regulation, translational regulation, degradation of the enzymes and phosphorylation
describe transcriptional regulation of HMG CoA reductase
When cholesterol is present in excess, the HMG-CoA reductase gene is transcribed 20X less via actions of transcription factor sterol regulatory element binding protein. Insulin increases expression of the enzyme and glucagon decreases
describe translational regulation of HMG CoA reductase
When cholesterol is present in excess, the translation rate of the mRNA encoding HMG-CoA reductase is 5X less than in the absence of cholesterol. mRNA half life decreases with excess cholesterol
describe degradative regulation of HMG CoA reductase
In excess cholesterol the half life of the enzyme HMG-CoA reductase decreases from 11 to 2 hours (targeted to proteasome)
describe phosphorylation regulation of HMG CoA reductase
AMP kinase phophorylates HMG-CoA reductase which inactivates the enzyme. Protein phosphatase removes the phosphate and this activates the enzyme.
MOA of statins
Structurally similar to mevalonate and as a result act as competitive inhibitors of HMG CoA reductase. The compound lovastatin is a natural product of fungi.
· Describe the key features of the structures of glycerophospholipids, sphyngomyelin and glycerosphingolipids and the general aspects of their synthesis.
glycerophospholipids: glycerol backbone, 2 fatty acids and a phosphate attached to an alcohol. Sphingomyelin: ceramide (sphingosine) backbone, a single fatty acid and a phosphate attached to choline. Glycerosphingolipids: sphingosine backbone, single fatty acid and a sugar moiety.
· Describe how the different glycerophospholipids are synthesized.
Backbone comes from phosphatidic acid. Then polar head group is added (formed de novo or come from diet), they are activated by CDP and attached to backbone. Another pathway involves base exchange where head groups are exchanged onto previously synthesized phospholipids
phosphatidyl serine, phosphatidylcholine, phosphatidylinositol
· List the important functions of phosphatidylcholine
Main component of lung surfactant and present in bile. Serves as reservoir of choline.
· List the important functions of phosphatidylinositol
important in signal transduction, membrane protein anchoring and as reservoir for arachadonic acid
· List the important functions of sphyngomyelin.
major structural lipid in nervous tissue,
examples of glycolipids
aka glycosphingolipids- cerebrosie, globoside and ganglioside