BIOC 503 - Biosynthesis of Complex Lipids & Prostaglandins & Other Eicosanoids

eicosanoids

prostaglandins and other bioactive lipids synthesized from 20C polyunsaturated fatty acids

prostaglandins synthesis

1. phospholipid containing arachidonate + phospholipase A2 = arachidonate + lysophospholipid

2. arachidonate + COX1 (cyclooxygenase activity aka forms rings and add peroxide) + 2O2 = PGG2

3. PGG2 + COX2 (peroxidase activity) = PGH2

4. PGH2 precursors to prostaglandins and thromboxane

non-steroidal anti-inflammatory drugs

aka NSAIDs

Drugs including ibuprofen and acetylsalicylic acid (aspirin) treating pain, fever, and inflammation by inhibiting the COX1 enzyme aka blocking cyclooxygenase activity

• serine residue of COX enzyme acylated 

arachnoid acid

substrate for making prostaglandins using COX enzyme

leukotriene

type of eicosanoids formed by lipoxygenase enzyme without any ring structure formed in the final product

liver, adipose tissues

the synthesis of TAGs happens in the ___ (mainly from de novo synthesis) or in the ___ (mainly from lipoproteins)

glycerol-phosphate

The ____ moiety used to synthesize TAGs either comes from glycolysis (dihydroxyacetone phosphate + NADH) or from lipolysis (glycerol + ATP) 

glycerophospholipids

the synthesis of ___ branches off of the TAGs synthesis pathway at 2 different points: PA or DAG

synthesis of PI, OG and cardiolipin

Formation of anionic head compounds (___)

Attachment of a head group to PA by activation of PA to DAG-CDP (PA-CMP)

• cytidyl transferase adds cytidine phosphate to the phosphate already in 3rd position of PA

• PI or PG synthase adds inositol and glycerol respectively to frorm final product

Kennedy pathway

Formation of PC and PE

Attachment of head group to DAG by activation of head group (forming head-CDP)

• uses ATP to add phosphate to choline (choline kinase)

• add cytidine to phosphate choline (cytidyl transferase)

• add CDP-choline to DAG to form PC (phosphocholine transferase)

cytidine phosphate

CDP

head group exchange

PS synthesized by ___ with PC or PE

sphingolipids synthesis

1. palmitoyl-CoA + Serine + SPT = CoA + CO2 + B-ketosphinganine

2. B-ketosphinganine + NADPH + reductase = sphinganine + NADP+

3. shinganine + fatty-acyl-CoA + Ceramide synthase = N-acylsphinganine

4. N-acylsphinganine + mixed functions oxidase = ceramide

5. ceramide + UDP-Glucose = cerebroside + UDP

5. ceramide + phosphatidylcholine = sphingomyelin + diacylglycerol 

Serine Palmitoyltransferase

aka SPT rate limiting enzyme in synthesis of sphingolipids

• turns palmityl-CoA into B-ketosphinganine 

ceramide syntahse

aka CerS

specific enzyme in sphingolipids synthesis turning Sphinganine into N-acylsphinganine and ultimately ceramide

• aka amidation