CHAPTER 29 Lipid Synthesis: Storage Lipids, …rcarlson/bcmb3100/Chap29.pdfCHAPTER 29 Lipid Synthesis: Storage Lipids, Phospholipids, and Cholesterol Problems: 3-6, 8, 12, 14-18, 21-22,

CHAPTER 29Lipid Synthesis: Storage Lipids, Phospholipids, and Cholesterol

Problems: 3-6, 8, 12, 14-18, 21-22, 27, 29.

29.1 Phosphatidate is Precursor of Storage and Membrane Lipids

Synthesis of TGs and neutral phospholipids

Synthesis of acidic phospholipids

• Interconversions of phosphatidyl-ethanolamine (PE), phosphatidylserine(PS)

29.2 Cholesterol Synthesis

2 Acetyl CoA 

Acetoacetyl CoA 

Thiolase

HMG‐CoA synthase

SCoA

O

OH

O OH

CH3

CH2OHOH

O OH

CH3 OPO3PO3CH2

CH3

‐3

CH3CH3

CH3 CH3 CH3

CH3 CH3 CH3

CH3

CH3

CH3

H

CH3

CH3

OH

Isopentenylpyrophosphate

Mevalonic acid

Squalene3‐hydroxy‐3‐methylglutaryl 

CoA

Cholesterol

HMG‐CoA reductase

3 steps

20 steps

3 steps

Isoprene unit

29.3 Regulation of Cholesterol Synthesis

• Via synthesis of HMG CoA reductase mRNA (transcription).

• Via rate of translationof HMG CoA reductase mRNA (nonsterol mevalonatemetabolites).

• Via degradation of HMG CoA reductase.

29.4 Transport of Cholesterol and Triacylglycerol

ChylomicronsChylomicron remnantsVLDL, IDL,LDL, HDL

VLDL lipoproteinLDL lipoprotein

Lipoprotein transport

LDL metabolism

LDL receptor mediated

endocytosis

LDL receptor defect.

Statins inhibit HMG-CoA reductase

29.5 Cholesterol is the Precursor of Steroid Hormones

Bile salts, steroid hormones, vitamin D

Bile salt: detergent for solubilizing dietary lipids.

• Progesterone: maintenance of pregnancy• Androgen: male hormone (also anabolic steroids).• Estrogens: female hormone• Glucocorticoid: gluconeogensis and glycogen synthesis.• Mineralglucocorticoids: salt regulation, blood pressure.

Vitamin D

Elmer McCollum tested cod liver oil with the vitamin A removed the dogs suffering from rickets still recovered. He named his new discovery vitamin D for the 4th letter of the alphabet (vitamin D was the 4th vitamin discovered). Research continued on this substance and it was eventually discovered that a certain form of vitamin D is created in the human body through exposure to sunlight (UV light). Thanks to the hard work of the scientists working on the discovery of vitamin D rickets is virtually eliminated from developed countries.

Hector DeLuca’s laboratory, Univ. of Wisconsin, demonstrated that vitamin D itself is biologically inactive and must be modified by sequential action by the liver and kidney to prepare the hormone derived from vitamin D, namely 1,25‐dihydroxyvitamin D3.