Lipid and Steroid Biosynthesis

Complex lipids overview in organisms

sphingolipids and triacylglycerols made in eukaryotes

Phosphotitylethonamine maine one in prokaryotes

No PC, PI, sphingo, Chloesterol in E.Coli

Glycerol lipid biosynthesis

CTP makes CDP complexes

Phosphatidic acid (PA) made into DAG or CDP-DAG

CDP-choline and CDP-ethanolamine makes PC/PE

CDP-DAG makes?

PI

PG

Cardiolipin

Plasmalogen Biosynthesis

comes from DHAP

Acylation activates an exchange rxn to make ether linkage

ketone reduction follows

CDP-ethanolamine delivers headgroup

desaturase produces double bond in chain

Sphingolipid Biosynthesis

make up mylein sheath

come from serine + palmitoyl-CoA

3-ketosphinganine synthase is PLP-dependent

Ketone is reduced by NADPH

acylation then double bond

Makes ceramide

Ceramides make?

Sphingomyelin

Cerebroside + more sugar → gangliosides

Ganglioside degradation

lysosome

aminohexadase

inhibition leads to death and engorged lysosome

Cholesterol biosynthesis

begins in cytosol

thiolase rxn

HMG CoA rxn

HMG-CoA reductase rate limiting step

Targeted for cholesterol lowering staten drugs

know number of carbons

Regulation of HMG-CoA reductase

Phosphorylation inactivates

Short half life

gene expression controlled by chloesterol levels

30-C Squalene synthesis

Made from mevalonate

6-C Mevalonate decarbed to 5-C isopentyl PP

6 of these make squalene

3 makes farnesyl PP

2 farnesyl PP makes squalene

BLOCH synthesis

Cholesterol from Squalene

Squalene monooxygenase converts squalene to squalene-2, 3-epoxide

cyclase converts epoxide to lanosterol

IN ER

dont have to know 20 steps

Vit D from 7-Dehydrochloesterol

Regulation of Cholesterol Synthesis

HMG-CoA reductase

Lovastatin (LACTONE) inhibits HMG-CoA

Compactin

Lipid Transport & Lipoproteins

Lipoproteins have cluster of lipids around them

HDL-brings cholesterol back to liver

VLDL → LDL -exported from liver to deliver fats

Chylomicrons form in intestines

Lipoproteins

Chylomicrons- carry TAGs

LDL- carry cholesterol

Cholesterol : HDL ratio > 4.5 = heart disease

Lipoprotein degradation

Degraded by lipases → releases fats

LDL binds to LDL receptors on liver

Processed to VLDL or HDL

LDL receptor

Binds LDL by N terminus

Single TMS

Sugar domains

Bile Acid biosynthesis

synthesized from cholesterol conjugation with taurocholic or glycocholic acid

makes Glycocholate or Taurocholate

Oxidation of cholesterol

Steroid Hormone Synthesis

Desmolase forms pregnenolone

Moves from Mitochondria to ER to form progesterone

Progesterone forms test and Estrogen

Anabolic steroids cause Hirsutism