The pathway of dietary triacylglycerols from the mouth to their ultimate biochemical fate in the body is not as straightforward as that of carbohydrates.

• Complications arise because triacylglycerols are not water-soluble, but nevertheless must enter an aqueous environment.

• To be moved around within the body by the blood and lymph systems, they must be dispersed and surrounded by a water-soluble coating, a process that must happen more than once as triacylglycerols travel along their metabolic pathways.

• During these travels, they are packaged in various types of lipoproteins, which consist of droplets of hydrophobic lipids surrounded by phospholipids, proteins, and other molecules with their hydrophilic ends to the outside. Lipoproteins are special forms of micelles.

When partially digested food leaves the stomach, it enters the upper end of the small intestine (the duodenum), where its arrival triggers the release of pancreatic lipases— enzymes for the hydrolysis of lipids.

• The gallbladder simultaneously releases bile, a mixture that is manufactured in the liver and stored in the gallbladder until needed. Among other components, bile contains cholesterol and cholesterol-derived bile acids, both of which are sterols, and phospholipids.

By the time dietary triacylglycerols enter the small intestine, they are dispersed as small, greasy, insoluble droplets, and for this reason enzymes in the small intestine cannot attack them.

• It is the job of the bile acids and phospholipids to emulsify the triacylglycerols by forming micelles similar to soap micelles.

• The major bile acid is cholic acid, and the structure of its anion closely resembles soaps because it contains both hydrophilic and hydrophobic regions allowing it to act as an emulsifying agent.

The lipids used in the body’s metabolic pathways have three sources:

(1) from the digestive tract as food is broken down

(2) from adipose tissue, where excess lipids have been stored

(3) from the liver, where lipids are synthesized.

To become water-soluble, fatty acids released from adipose tissue associate with albumin, a protein found in blood plasma that binds up to 10 fatty acid molecules per protein molecule. All other lipids are carried by lipoproteins.

Lipids are less dense than proteins, the density of lipoproteins depends on the ratio of lipid to protein. Therefore, lipoproteins are arbitrarily divided into five major types distinguishable by their composition and densities.

• Chylomicrons, which transport dietary lipids, carry triacylglycerols through the lymphatic system into the blood and thence to the liver for processing. These are the lowest-density lipoproteins (less than 0.95 g>cm3 ) because they carry the highest ratio of lipid to protein.

• The four denser lipoprotein fractions have the following roles:

  • Very low-density lipoproteins (VLDLs) (0.96–1.006 g>cm3) carry triacylglycerols from the liver (where they are synthesized) to peripheral tissues for storage or energy generation.

  • Intermediate-density lipoproteins (IDLs) (1.007–1.019 g>cm3) carry remnants of the VLDLs from peripheral tissues to the liver for use in synthesis.

  • Low-density lipoproteins (LDLs) (1.020–1.062 g>cm3) transport cholesterol from the liver to peripheral tissues, where it is used in cell membranes or for steroid synthesis (and is also available for formation of arterial plaque).

  • High-density lipoproteins (HDLs) (1.063–1.210 g>cm3) transport cholesterol from dead or dying cells to the liver, where it is converted to bile acids. The bile acids are then available for use in digestion or are excreted via the digestive tract when in excess.

Fate of Dietary Triacylglycerols:

• Triacylglycerols undergo hydrolysis to fatty acids and glycerol.

• Fatty acids undergo:

• Resynthesis of triacylglycerols for storage

• Conversion to acetyl-CoA

• Glycerol is converted to glyceraldehyde 3-phosphate and DHAP, which participate in:

• Glycolysis—energy generation

• Gluconeogenesis—glucose formation

• Triacylglycerol synthesis—energy storage

• Acetyl-CoA participates in:

• Triacylglycerol synthesis

• Ketone body synthesis

• Synthesis of sterols and other lipids

• Citric acid cycle and oxidative phosphorylation.

Triacylglycerol Synthesis:

• After a meal, blood glucose levels rise, and glucagon levels drop. Glucose enters cells, and the rate of glycolysis increases.

  • Under these conditions, insulin activates the synthesis of triacylglycerols for storage. The reactants in triacylglycerol synthesis are glycerol 3-phosphate and fatty acid acyl groups carried by coenzyme A.

• Triacylglycerol synthesis proceeds by transfer of first one and then another fatty acid acyl group from coenzyme A to glycerol 3-phosphate.

  • The reaction is catalyzed by acyl transferase, and the product is phosphatidic acid.

• Next, the phosphate group is removed from phosphatidic acid by phosphatidic acid phosphatase to produce 1,2-diacylglycerol.

  • In the presence of acyl transferase, the third fatty acid group is then added to give a triacylglycerol.

Oxidation of fatty acids:

Once a fatty acid enters the cytosol of a cell that needs energy, three successive processes occur. 1. Activation :The fatty acid is activated by conversion to fatty acyl-CoA. This activation, which occurs in the cytosol, serves the same purpose as the first few steps in oxidation of glucose by glycolysis.

• Initially, some energy from adenosine triphosphate (ATP) must be invested in converting the fatty acid to fatty acyl-CoA, a form that breaks down more easily.

• Since only one phosphate ester bond is broken in the reaction, the activation energy used is for one ATP only.

2. Transport :The fatty acyl-CoA, which cannot cross the mitochondrial membrane by diffusion, is transported by carnitine from the cytosol into the mitochondrial matrix, where energy generation occurs.

• Carnitine, an amino-oxy acid, undergoes an ester-formation exchange reaction with the fatty acyl-CoA, resulting in a fatty acylcarnitine ester that moves across the membrane into the mitochondria by facilitated diffusion.

• There, another ester-formation exchange reaction regenerates the fatty acyl-CoA and carnitine.

3. Oxidation :The fatty acyl-CoA is oxidized by enzymes in the mitochondrial matrix to produce acetyl-CoA, nicotinamide adenine dinucleotide (NADH), and flavin adenine dinucleotide (FADH2 ). -

• The oxidation occurs by repeating the series of four reactions, which make up the B-oxidation pathway. Each repetition of these reactions cleaves a 2-carbon acetyl group from the end of a fatty acid acyl group and produces one acetyl-CoA.

• This pathway is a spiral because the shortened long-chain fatty acyl group must continue to return to the pathway until each pair of carbon atoms is removed.

The Beta-Oxidation Pathway :The name beta oxidation refers to the oxidation of the carbon atom beta to the thioester linkage in two steps of the pathway.

• STEP 1: The first B oxidation Acyl-CoA dehydrogenase and its coenzyme FAD remove hydrogen atoms from the carbon atoms a and b to the carbonyl group in the fatty acyl-CoA, forming a carbon–carbon double bond. These hydrogen atoms and their electrons are passed directly from FADH2 to coenzyme Q so that the electrons can enter the electron transport chain.

• STEP 2: Hydration Enoyl-CoA hydratase adds a water molecule across the newly created double bond to give an alcohol with the ¬OH group on the b carbon.

• STEP 3: The second B oxidation The coenzyme NAD+ is the oxidizing agent for conversion of the b¬OH group to a carbonyl group by beta-hydroxyacyl-CoA dehydrogenase.

• STEP 4: Cleavage to remove an acetyl group An acetyl group is split off by thiolase (acyl-CoA acetyltransferase) and attached to a new coenzyme A molecule, leaving behind an acyl-CoA that is two carbon atoms shorter.

Ketone bodies: Compounds produced in the liver that can be used as fuel by muscle and brain tissue; for example, 3-hydroxybutyrate, acetoacetate, and acetone.

Ketogenesis :The synthesis of ketone bodies from acetyl-CoA.

Fatty acid biosynthesis from acetyl-CoA, a process known as lipogenesis, provides a link between carbohydrate, lipid, and protein metabolism.

Because acetyl-CoA is an end product of carbohydrate and amino acid catabolism, using it to make fatty acids allows the body to divert the energy of excess carbohydrates and amino acids into storage as triacylglycerols.