Lipogenic tissue

Malonyl-CoA is also involved in the regulation of fatty acid oxidation, via inhibition of carnitine palmitoyltransferase. In non-lipogenic tissues, the only role of the carboxylase is provision of malonyl-CoA for regulation of the rate of fatty acid oxidation. 

Menendez, J.A., Ropero, S., Mehmi, I., Atlas, E., Colomer, R., and Lupu, R., Overexpression and hyperactivity of breast cancer-associated fatty acid synthase (oncogenic antigen-519) is insensitive to normal arachidonic fatty acid-induced suppression in lipogenic tissues but it is selectively inhibited by tumoricidal alpha-linolenic and gamma-lrnolenic fatty acids a novel mechanism by which dietary fat can alter mammary tumorigenesis, Int. J. Oncol., 24, 1369, 2004. 

Mouse Scdl gene was first isolated from differentiated 3T3-L1 adipocytes and is ubiquitously expressed with the highest expression in lipogenic tissues including liver, adipose tissue, and sebaceous glands. Scdl desaturates saturated fatty acyl-CoA with 12-19 carbons with the highest preference for the conversion of stearoyl-CoA (C18 0) into oleoyl-CoA(C18 l)[ll],... 

The acetyl-CoA can be converted to malonyl-CoA via the aetion of acetyl-CoA carboxylase (ACC biotin-dependent enzyme) [101]. Two isoforms have been identified, ACCl and ACC2, with ACCl being principally expressed in lipogenic tissues such as adipose tissue and liver, while ACC2 is predominantly expressed in oxidative tissues like heart and skeletal muscle [102]. 

In humans, the liver is a major lipogenic tissue. The liver is able to transform excess carbohydrate or protein into fat (remember, when we eat too much of anything we get fat ). Eatty acid substrates for hepatic triglyceride production are derived from three sources (Fig. 5) (1) a continuous supply of albumin-bound fatty acid to the liver, primarily from adipose tissue triglyceride stores (after a meal this source drops, due to the antilipolytic action of insulin), (2) dietary fat already transported in chylomicrons delivered to the liver, and (3) carbohydrate in excess of the liver s capacity for storage as glycogen. 

The liver is an important lipogenic tissue and exports newly synthesized triglyceride in VLDL particles. 

Much of our need for fatty acids as constituents of phospholipids and other complex lipids is met by the diet. In addition, certain lipogenic tissues are capable of the de novo synthesis of fatty acids (Figure 6). These tissues include liver (hepatocytes), adipose tissue, and lactating mammary gland. Much of the fatty acids synthesized by all three tissues is incorporated into triacylglycerol. Hepatic synthesis is primarily for export to other tissues (in very low-density lipoproteins), while synthesis in adipocytes and mammary gland is for local storage. 

The carbon used for fatty-acid synthesis typically derives from the products of glycolysis. The end product of glycolysis, pyruvate, enters the mitochondria and becomes the substrate for two separate reactions. In one, pyruvate is decarboxylated via the pyruvate dehydrogenase complex, yielding acetyl-CoA. Lipogenic tissues also contain another mitochondrial enzyme, pyruvate carboxylase, which converts pyruvate to the four-carbon acid oxaloace-tate (OAA). Acetyl-CoA and oxaloacetate condense to form the six-carbon acid citrate. As citrate accumulates within the mitochondrion, it is exported to the cytoplasm, where it is converted back to oxaloacetate and acetyl-CoA. Cytoplasmic acetyl-CoA is the fundamental building block for de novo synthesis of fatty acids. 

---