Fatty Acids Metabolism

Triglyceride (= triacylglycerol) hydrolysis in adipocytes is subject to complex hormonal regulation (A). Besides by glu-cagon, growth hormones, and others, hormone-sensitive lipase is activated, in particular, by catecholamines released during times of heightened energy need. Hormone-sensitive lipase is activated via a p-receptor and subsequent formation of the second messenger cAMP in the adenylate cyclase system. Hormone-sensitive lipase releases free fatty acids (FFA) from tri- and di-glycerides; there is a separate lipase specific to monoglyceride hydrolysis. Glycerol reaches the liver through the blood stream where it is used predominantly for gluconeogenesis. Short-chain FFA are dissolved in plasma, longer-chain FFA are bound to albumin. With the exception of the brain and erythrocytes, all tissues are able to use these FFA for energy. Gynoid adipocytes, which are frequently found in the upper thighs and buttocks of women additionally contain a2-receptors that inhibit cAMP synthesis. Consequently, lipase activation through catechol-amines occurs at a greatly reduced rate in those adipocytes.

Fatty acid breakdown is intensified in the liver while FFA plasma levels are elevated (B). After being brought into the cells, fatty acids are activated to form acyl-CoA—a process that requires ATP— and are transported to the mitochondria with the help of carnitine. During subsequent p-oxidation, sections are cleaved off from the carboxyl end, two carbon atoms at a time, to form acetyl-CoA. There are separate pathways for unsaturated and branched fatty acids, as well as those with odd numbers of carbon atoms. A similar breakdown of long-

chain fatty acids takes place inside the hepatocyte peroxisomes. During times of high acetyl-CoA availability, for instance from increased lipo-lysis during fasting or starvation, or in patients with diabetes mellitus, two acetyl-CoA molecules may condense into acetoacetyl-CoA. Acetoacetyl-CoA is used to form ketone bodies (e.g., acetacetate), an energy source for the tissues that even the brain is able to use, albeit after a short adaptation phase. The biosynthesis of fatty acids, lipogen-esis, occurs in many tissues, however, postprandially primarily in liver and fatty tissues. During glycolysis pyru-vate is formed, taken to the mitochondria, and decarboxylated to acetyl-CoA. Acetyl-CoA is subsequently returned to the cytosol via the citrate-malate shuttle. Inside the cytosol acetyl-CoA carboxylase, a rate-determining enzyme, carboxylates it to malonyl-CoA. C2 units are then assembled into palmitate (16:0) by a fatty acid synthase complex. Palmitate can be elongated in the endoplasmic reticulum.

The regulation of fatty acid metabolism is determined primarily by the ratio of available FFA compared to the size of the mitochondrial acetyl-CoA pool—besides being subject to a multitude of hormonal influences. At elevated FFA levels (e. g., during fasting or starvation) carnitine palmitoyl-trans-ferase is activated, enabling the transport of activated fatty acids (acyl-CoA) into the mitochondria with subsequent elevated ß-oxidation, more acetyl-CoA, and increased ketogenesis. At the same time, FFA inhibit lipogenesis while postprandial insulin secretion, on the other hand, stimulates acetyl-CoA carboxy-lase. The increase of malonyl-CoA in turn inhibits the transport of acyl-CoA into the mitochondria and therewith fatty acid breakdown.

Fatty Acid Metabolism 103

- A. Lipolysis in Adipocytes -

Gynoid adipocytes

All adipocytes

- A. Lipolysis in Adipocytes -

Gynoid adipocytes

All adipocytes

Malonyl Coa Mitochondrion

Hormonesensitive lipase

Monoacyl-glycerol lipase

H2O FFA H2O FFA H2O FFA

Hormonesensitive lipase

Monoacyl-glycerol lipase

H2O FFA H2O FFA H2O FFA

B. Fatty Acid Metabolism in Hepatocytes

Blood

Lipogenesis Malonyl-CoA -► Palmitate

Acylglycerol

Acetyl-CoA

Acetyl-CoA carboxylase alate

Pyruvate - Carbohydrates

Cytoplasm

Lipogenesis Malonyl-CoA -► Palmitate

Acylglycerol

Acetyl-CoA

Acetyl-CoA carboxylase alate

Pyruvate - Carbohydrates

Cytoplasm

Palmitate Metabolism
Good Carb Diet

Good Carb Diet

WHAT IT IS A three-phase plan that has been likened to the low-carbohydrate Atkins program because during the first two weeks, South Beach eliminates most carbs, including bread, pasta, potatoes, fruit and most dairy products. In PHASE 2, healthy carbs, including most fruits, whole grains and dairy products are gradually reintroduced, but processed carbs such as bagels, cookies, cornflakes, regular pasta and rice cakes remain on the list of foods to avoid or eat rarely.

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