2. Lipids
are a heterogeneous group of water-insoluble (hydrophobic) organic molecules that can be extracted from tissues by nonpolar solvents.
Body lipids are generally found compartmentalized, as in the case of membrane-associated lipids or droplets of triacylglycerol in white adipocytes, or transported in plasma in association with protein, as in lipoprotein particles or on albumin.
Lipids are
Major source of energy for the body
Provide the hydrophobic barrier that permits partitioning of the aqueous contents of cells and subcellular structures.
Some fat-soluble vitamins have regulatory or coenzyme functions. 18 2

3. Most of the lipids found in the body fall into the categories of
Fatty acids
Triacylglycerols; glycerophospholipids
Sphingolipids;
Eicosanoids;
Cholesterol,
Bile salts,
Steroid hormones;
Fat-soluble vitamins.
Fatty acids, which are stored as triacylglycerols, serve as fuels, providing the body with its major source of energy (Fig. VI.1).
Polyunsaturated fatty acids containing 20 carbons form the eicosanoids, which regulate many cellular processes (Fig. VI.2).

5. Cholesterol adds stability to the phospholipid bilayer of membranes
Cholesterol adds stability to the phospholipid bilayer of membranes. It serves as:
The precursor of the bile salts, detergent-like compounds that function in the process of lipid digestion and absorption (Fig. VI.3).
Cholesterol also serves as the precursor of the steroid hormones, which have many actions, including the regulation of metabolism, growth, and reproduction.
The fat-soluble vitamins are lipids that are involved in such varied functions as:
Vision,
Growth,
Differentiation (vitamin A),
Blood clotting (vitamin K),
Prevention of oxidative damage to cells (vitamin E), and calcium metabolism (vitamin D).

6. Triacylglycerols, the major dietary lipids, are digested in the lumen of the intestine.
The initial digestive products,
free fatty acids and
2-monoacylglycerol,
They are reconverted to triacylglycerols in intestinal epithelial cells, packaged in lipoproteins known as chylomicrons , and secreted into the lymph.
Ultimately, chylomicrons enter the blood, serving as one of the major blood lipoproteins.

7. Structure of a triacylglycerol
Structure of a triacylglycerol. The glycerol moiety is highlighted, and its carbons are numbered.

9. The Chylomicrons
Chylomicrons are the largest lipoproteins and the least dense because of their rich triacylglycerol content.
They are synthesized from dietary lipids within the epithelial cells of the small intestine and then secreted into the lymphatic vessels draining the gut.
They enter the bloodstream via the left subclavian vein (Each subclavian vein is a continuation of the axillary vein and runs from the outer border of the first rib to the medial border of anterior scalene muscle).
The major apoproteins of chylomicrons are apoB-48, apoCII, and apoE.
Within the intestinal epithelial cells, the fatty acids and 2 monoacylglycerols are condensed by enzymatic reactions in the smooth endoplasmic reticulum to form triacylglycerols.

10. Example of the structure of a blood lipoprotein.
Lipoproteins contain phospholipids and proteins on the surface, with their hydrophilic regions interacting with water. Hydrophobic molecules are in the interior of the lipoprotein. The hydroxyl group of cholesterol is near the surface. In cholesterol esters, the hydroxyl group is esterified to a fatty acid. Cholesterol esters are found in the interior of lipoproteins and are synthesized by reaction of cholesterol with an activated fatty acid.

11. The major apoprotein associated with chylomicrons as they leave the intestinal cells is B-48 (Fig. 1).
The B-48 apoprotein is structurally and genetically related to the B-100 apoprotein synthesized in the liver that serves as a major protein of another lipid carrier, very-low-density lipoprotein (VLDL).

12. Fig. 1. Fate of chylomicrons
Fig. 1. Fate of chylomicrons. Chylomicrons are synthesized in intestinal epithelial cells, secreted into the lymph, pass into the blood, and become mature chylomicrons. On capillary walls in adipose tissue and muscle, lipoprotein lipase (LPL) activated by ApoCII digests the triacylglycerols (TG) of chylomicrons to fatty acids and glycerol. Fatty acids (FA) are oxidized in muscle or stored in adipose cells as triacylglycerols. The remnants of the chylomicrons are taken up by the liver by receptor-mediated endocytosis. Lysosomal enzymes within the hepatocyte digest the remnants, releasing the products into the cytosol.

13. Fatty Acids Are Alkyl Chains Terminating in a Carboxyl Group
Fatty acids consist of an alkyl chain with a terminal carboxyl group, the basic formula of completely saturated species being CH3-(CH2)n COOH.
The important fatty acids for humans have relatively simple structures, although in some organisms they may be quite complex, containing cyclopropane rings or extensive branching.
Unsaturated fatty acids occur commonly in humans, with up to six double
bonds per chain, these being almost always of the cis configuration. Most fatty acids in humans are C16, C1s, or C26, but several with longer chains
occur principally in lipids of the nervous system.
These include nervonic acid and a C22 acid with six double bonds.

14. Most Fatty Acids in Humans Occur as Triacylglycerols
Fatty acids occur primarily as esters of glycerol, as shown in Figure 2, when they
are stored for future use.
Compounds with one (monoacylglycerols) or two (diacylglycerols) acids esterified occur only in relatively minor amounts and largely as metabolic intermediates in biosynthesis and degradation of glycerol-containing lipids.
Most fatty acids in humans exist as triacylglycerols, in which all three hydroxyl
groups on glycerol are esterified with a fatty acid
These compounds have been called "neutral fats or triglycerides." There are other types of "neutral fats" in the body, and the terms "monoglyceride," "diglyceride," and "triglyceride" are chemically incorrect and should not be used

15. Fig. 2
Acylglycerols.

16. SOURCES OF FATTY ACIDS
Both diet and biosynthesis supply the fatty acids needed by the human body for energy and for construction of hydrophobic parts of biomolecules. Excess dietary
protein and carbohydrate are readily converted to fatty acids and stored as
triacylglycerols.
Various animal and vegetable lipids are ingested, hydrolyzed at least partially by digestive enzymes, and absorbed through the intestinal mucosa to be distributed through the body, first in the lyrmphatic system and then in the bloodstream.
In humans most of the fatty acids are either saturated or contain only one double bond. Although they are readily catabolized by appropriate enzymes and cofactors, they are fairly inert chemically.
The highly unsaturated fatty acids in tissues are much more susceptible to oxidation.

17. Formation of Malonyl CoA is the Commitment
Step of Fatty Acid Synthesis
The reaction that commits acetyl CoA to fatty acid synthesis is its carboxylartion to malonyl coA by the en4rme acetyl-coA carboxylase (Figure 3).
This reaction is similar in many ways to carboxylation of pyruvate, which is catalyzed by pyruvate carboxylase and starts the process of gluconeogenesis.
The reaction requires ATP and HCO3- as the source of CO2. As with pyruvate carboxylase, the first step is formation of activated CO2 on the biotin moiety of acetyl-CoA carboxylase using energy from ATP This is then transferred to acetyl CoA.
Acetyl-CoA carboxylase, a key control point in the overall synthesis of fatty acids, can be isolated in a protomeric state that is inactive. The protomers aggregate to form enzymatically active polymers upon addition of citrate in vitro. Palmitoyl CoA in vitro inhibits the enzyme.

18. Figure 3
Acetyl-CoA carboxylase reaction.

19. Oxidation of Fatty Acids and Ketone Bodies
During overnight fasting, fatty acids become the major fuel for cardiac muscle, skeletal muscle, and liver. The liver converts fatty acids to ketone bodies (acetoacetate and β-hydroxybutyrate), which also serve as major fuels for tissues (e.g., the gut).
The brain, which does not have a significant capacity for fatty acid oxidation, can use ketone bodies as a fuel during prolonged fasting.
Fatty acids are generally classified as very-long-chain length fatty acids (greater than C20 ), long-chain fatty acids (C12–C20), medium-chain fatty acids (C6–C12), and short-chain fatty acids (C4).

20. ATP is generated from oxidation of fatty acids in the pathway of β-oxidation.
Between meals and during overnight fasting, long-chain fatty acids are released from adipose tissue triacylglycerols.
They circulate through blood bound to albumin (Fig. 4).
In cells, they are converted to fatty acyl CoA derivatives by acyl CoA synthetases. The activated acyl group is transported into the mitochondrial matrix bound to carnitine, where fatty acyl CoA is regenerated.
In the pathway of β-oxidation, the fatty acyl group is sequentially oxidized to yield FAD(2H), NADH, and acetyl CoA.
Subsequent oxidation of NADH and FAD(2H) in the electron transport chain, and oxidation of acetyl CoA to CO2 in the TCA cycle, generates ATP from oxidative phosphorylation.

21. Many fatty acids have structures that require variations of this basic pattern.
Long-chain fatty acids that are unsaturated fatty acids generally require additional isomerization and oxidation–reduction reactions to rearrange their double bonds during β-oxidation.
Metabolism of water-soluble medium-chain-length fatty acids does not require carnitine and occurs only in liver.
Odd-chain-length fatty acids undergo -oxidation to the terminal three-carbon propionyl CoA, which enters the TCA cycle as succinyl CoA.

22. Fatty acids that do not readily undergo mitochondrial -oxidation are
oxidized first by alternate routes that convert them to more suitable substrates or to urinary excretion products.
In the liver, much of the acetyl CoA generated from fatty acid oxidation is converted to the ketone bodies, acetoacetate and -hydroxybutyrate, which enter the blood (see Fig. 4).
In other tissues, these ketone bodies are converted to acetyl CoA, which is oxidized in the TCA cycle. The liver synthesizes ketone bodies but cannot use them as a fuel.

23. Fig. 4.
Overview of mitochondrial long-chain fatty acid metabolism.
Fatty acid binding proteins (FaBP) transport fatty acids across the plasma membrane and bind them in the cytosol.
(2) Fatty acyl CoA synthetase activates fatty acids to fatty acyl CoAs.
(3) Carnitine transports the activated fatty acyl group into mitochondria.
(4) -oxidation generates NADH,
FAD(2H), and acetyl CoA
(5) In the liver, acetyl CoA is converted to ketone bodies