Saturday, March 29, 2008

Fat Metabolism

Adenosine Triphosphate (ATP) is a compound used to exchange or supply energy for endergonic processes. Endergonic processes are those in which energy is absorbed in the form of work- energy is required and leads to the formation of molecular bonds, which results in decreased entropy (useless energy). ATP is hydrolysed by either removing 1 terminal phosphate (ATP ---> ADP + Pi) or removing 2 terminal phosphates (ATP ---> AMP + Pi).

Skeletal muscles are very efficient at converting chemical energy into mechanical energy with little waste (30-50%). ATP is regenerated from Creatine Phosphate during exercise. Creatine Phophate can quickly release a phosphate group, which can react with ADP to create the ATP necessary for muscle contraction. At rest, normal cell metabolism resynthesises ATP, which in turn resynthesises Creatine Phosphate.

Dietary fat is digested, then stored as triglycerides, which is the major fuel source stored in the body. A triglyceride is a glycerol molecule with 3 fatty acids attached. Triglycerides are non-polar (meaning there is equal sharing of electrons between two atoms). Chlyomicrons are large lipoprotein particles that give the triglycerides a polar coat and transport them to adipose tissue. The enzyme lipoprotein lipase is stimulated by insulin and stores the triglyceride in the adipose tissue.

The release of triglycerides from fatty tissue, when needed, is catalyzed by the enzyme mobilisng lipase, which is stimulated by glucagon and adrenaline. The triglycerides are transported via attachment to the major protein in circulation, albumin, to the tissue for oxidation.

Triglycerides make up about 70% of the body's energy reserves due to the efficiency with which they are stored and their ability to be highly reduced. Since they are anhydrous (stored without water due to their non-polar nature), triglycerides tend to be compact and light. Vast quantities of triglycerides can be stored in less space. Since they are a largely hydrocarbon chain (16-20 covalently linked methyl groups), they are highly reduced and capable of yielding a large supply of energy (40 J/g as compared to 18 J/g glycogen).

B-Oxidation of Fatty Acids occurs within the mitochondria of the liver and muscles. During sustained exercise, this cyclic chain provides a major source of energy in slow-twitch muscles. Each cycle of this chain of reactions results in 2 carbohydrates hydrolysed into molecules of Acetyl CoA from a fatty acid chain. Each cycle of the chain also contains NAD ---> NADH and FAD ---> FADH. The NADH and FADH are then oxidised to the electron transport chain and coupled with ATP production, while the Acetyl CoA molecules are converted into CO2 in the Citric Acid Cycle, then participate in the electron transport chain, coupled with ATP production.

Ketone Bodies are 4-carbon units that are oxidised in an alternate method of using Acetyl CoA formed in B-oxidation. In this process, Acteyl CoA is converted to acetoacetate in the liver, then further reduced to b-hydroxybutyrate. Acetoacetate is preferred as a source of energy over glucose by heart muscle and the renal cortex. The brain prefers glucose, but can use acetoacetate if necessary, as during starvation. Fatty acids can't enter neural tissue, so acetoacetate is regarded as a water-soluble, easily-transportable version of Acetyl CoA. The efficiency of this mechanism as compared to B-oxidation is comparable.

Fatty Acid Synthesis occurs in the cytoplasm of cells. Cyclic reactions occur, resulting in the conversion of Acteyl CoA to 2-carbon units added to the fatty acid chain. This supplies fatty acids that are needed by the body but not supplied through the diet. The purpose of fatty acid synthesis is to convert excess dietary glucose to fatty acids for storage. Glucose is converted to Pyruvate through glycolysis, then to Acteyl CoA. If ATP is required, then Acetyl CoA is oxidised via the Citric Acid Cycle. If glucose intake exceeds the body's needs, then the Acetyl CoA is used in fatty acid synthesis in the liver or is stored as triglycerides in the adipose tissue.

The drawback to fat metabolism is that it requres oxygen. If energy is needed faster than oxygen can be delivered to the working muscles, then they switch to one of the less-efficient anaerobic pathways.

ATP - Adenosine Triphosphate. 1 phosphate ---> 7.3 kcal/mole

NADH - Nicotinamide Adenine Dinucleotide. Can transfer 2 electrons and 1 hydrogen ion to oxygen. --->52 kcal/mole.....3 ATP formed.

FADH2 - Flavin Adenine Dinucleotide. 43.4 kcal/mole......2 ATP formed.

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