CONCEPT MAP: THE GENERATION OF BIOCHEMICAL ENERGY
24.2 Lipoproteins for Lipid Transport
The lipids used in the body’s metabolic pathways have three sources. They enter the pathways (1) from the digestive tract as food is broken down; (2) from adipose tissue, where excess lipids have been stored; and (3) from the liver, where lipids are synthe- sized. Whatever their source, these lipids must eventually be transported in blood, an aqueous medium, as summarized in Figure 24.5.
S E C T I O N 2 4 . 2 Lipoproteins for Lipid Transport 755
KEY CONCEPT PROBLEM 24.1
Cholesterol (see structure in margin) and cholate (a bile acid anion, whose structure is shown on p. 754) are sterols with very similar structures. However, the roles they play in the body are different: Cholate is an emulsifier, whereas cholesterol plays an important role in membrane structure. Identify the small differences in their struc- tures that make them well suited to their jobs in the body. Given their similar struc- tures, can the roles of these molecules be reversed?
Acylglycerols
Chylomicrons
Lacteal (to bloodstream via lymphatic system) Free fatty acids
Partly hydrolyzed phospholipids
Smaller free fatty acids and acylglycerols,
glycerol Cholesterol
Triacylglycerols
Phospholipids
Capillary (to bloodstream via hepatic portal vein)
◀ Figure 24.4
Pathways of lipids through the villi.
CH3
CH3 H3C
H3C H3C
HO
Cholesterol
Lipids in diet
Fatty acids from storage in adipose
tissue
TAGs synthesized
in liver Digestion—
emulsification by bile acids
Bloodstream Transport by
chylomicrons
Transport by serum albumin
Transport by VLDLs
Cholesterol from dead cells
Transport by HDLs Cholesterol
synthesized in liver
Transport by LDLs
◀Figure 24.5 Transport of lipids.
Fatty acids released from storage are carried by albumin, which is a large protein. All of the other lipids are car- ried packaged in various lipoproteins.
The pathways of lipids through the villi and into the transport systems of the bloodstream and the lymphatic system are summarized in Figure 24.4.
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. (The role of lipoproteins in heart disease, where they are of great concern, is discussed in Chemistry in Action:
Lipids and Atherosclerosis on p. 757.)
Because lipids are less dense than proteins, the density of lipoproteins depends on their ratio of lipids to proteins. Therefore, lipoproteins can be arbitrarily divided into five major types distinguishable by their composition and densities. Chylomicrons, which are the only lipoproteins devoted to transport of lipids from the diet, carry tri- acylglycerols 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 lipids to proteins. The four denser lipoprotein fractions have the following roles:
• Very-low-density lipoproteins (VLDLs) 10.9691.006 g>cm32 carry triacylglycer- ols from the liver (where they are synthesized) to peripheral tissues for storage or energy generation.
• Intermediate-density lipoproteins (IDLs) 11.00791.019 g>cm32 carry remnants of the VLDLs from peripheral tissues back to the liver for use in synthesis.
• Low-density lipoproteins (LDLs) 11.02091.062 g>cm32 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) 11.06391.210 g>cm32 transport cholesterol from dead or dying cells back 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.
Worked Example 24.1 Digesting and Transporting Fats
Describe how the fat in an ice cream cone gets from the ice cream to a liver cell.
ANALYSIS Dietary fat from animal sources (such as the whole milk often found in ice cream) is primarily triacylglycerols with a small amount of cholesterol pres- ent. Cholesterol is not degraded in the digestive system. Fat-digesting enzymes are secreted by the pancreas and delivered via the common duct to the small intestine, along with bile acids. As discussed above, only free fatty acids and mono- and di- acylglycerols can cross the intestinal cell wall before being passed on to the blood stream. Smaller molecules such as some free fatty acids and glycerol diffuse across the cell membrane to enter the bloodstream; larger molecules must be delivered there in special packaging, called lipoproteins.
SOLUTION
As the ice cream cone is eaten, it passes through the mouth to the stomach, where mixing occurs. This mixing action promotes the formation of triacylglycerols into small droplets. No enzymatic digestion of lipids occurs in the stomach. When the stomach contents move to the small intestine, bile acids and pancreatic lipases are secreted into the mixture. The bile acids help to emulsify the fat droplets into micelles. Once micelles have formed, lipases hydrolyze the triacylglycerols to mono- and diacylglycerols; the hydrolysis also produces fatty acids. These three hydrolysis products cross into the cells lining the small intestine, are resynthesized into triacylglycerides, and are secreted into the bloodstream in the form of chylo- microns. Chylomicrons travel to the liver and enter cells for processing. The small amount of cholesterol in the ice cream will be directly absorbed, packaged into chylomicrons as well, and sent to the liver.
S E C T I O N 2 4 . 2 Lipoproteins for Lipid Transport 757
Lipids and Atherosclerosis
According to the U.S. Food and Drug Administration (FDA), and in agreement with many other authorities, there is “strong, con- vincing, and consistent evidence” for the connection between heart disease and diets high in saturated fats and cholesterol.
(Research has provided strong evidence that high dietary fat is one risk factor for certain types of cancer.)
Several points are clear:
• A diet rich in saturated animal fats leads to an increase in blood-serum cholesterol.
• A diet lower in saturated fat and higher in unsaturated fat can lower the serum cholesterol level.
• High levels of serum cholesterol are correlated with athero- sclerosis, a condition in which yellowish deposits (arterial plaque) composed of cholesterol and other lipid-containing materials form within the larger arteries. The result of ath- erosclerosis is an increased risk of coronary artery disease and heart attack brought on by blockage of blood flow to heart muscles or an increased risk of stroke due to blockage of blood flow to the brain.
Factors considered in an overall evaluation of an individual’s risk of heart disease are the following:
Risk factors for heart disease
High blood levels of cholesterol and low levels of high-density lipoproteins (HDLs)
Cigarette smoking High blood pressure Diabetes
Obesity
Low level of physical activity Family history of early heart disease
As discussed in Section 24.2, lipoproteins are complex assemblages of lipids and proteins that transport lipids through- out the body. If LDL (the so-called “bad” cholesterol) delivers more cholesterol than is needed to peripheral tissues, and if not enough HDL (the so-called “good” cholesterol) is present to remove it, the excess cholesterol is deposited in cells and arteries. Thus, the higher the HDL level, the less the likelihood of deposits and the lower the risk of heart disease. There is some evidence that a low HDL level (less than 35 mg>dL) may be the single best predictor of heart attack potential. Also, LDL has
the harmful potential to trigger inflammation and the buildup of plaque in artery walls. (Remember it this way—lowLDL is good; highHDL is good.)
Many groups recommend that individuals strive for the fol- lowing cholesterol levels in blood:
Total cholesterol 200 mg>dL or lower
LDL 130 mg>dL or lower
HDL 40 mg>dL or higher
To further assess the risk level represented by an individu- al’s cholesterol and HDL values, the total cholesterol/HDL ratio is calculated. The ideal ratio is considered to be 3.5. A ratio of 4.5 indicates an average risk, and a ratio of 5 or higher shows a high and potentially dangerous risk. The ratio overcomes the difficulty in evaluating the significance of, for example, a high cholesterol level of 290 mg>dL (negative) combined with a high HDL value of 75 mg>dL (positive). The resultant ratio of 3.9 indi- cates a low risk level.
Decreasing saturated fats and cholesterol in the diet, adopt- ing an exercise program, and not smoking constitute the first line of defense for those at risk. For those at high risk or for whom the first-line defenses are inadequate, drugs are available that prevent or slow the progress of coronary artery disease by lowering serum cholesterol levels. Among the drugs are indi- gestible resins (cholestyramine and colestipol) that bind bile ac- ids and accelerate their excretion, causing the liver to use up more cholesterol in bile acid synthesis. Another class of effective drugs is the statins (for example, lovastatin), which inhibit an enzyme crucial to the synthesis of cholesterol.
See Chemistry in Action Problems 24.60 through 24.63 at the end of the chapter.
CHEMISTRY IN ACTION
▲ Plaque. Deposits of cholesterol and associated lipids (known collectively as plaque) have partially blocked the flow of blood in this artery.
PROBLEM 24.2
What is arterial plaque? Why is it desirable to have a high HDL value and a relatively low LDL value? (See Chemistry in Action: Lipids and Atherosclerosis above.)