MCAT Biochemistry Review

Chapter 11: Lipid and Amino Acid Metabolism

Conclusion

At this point, we have examined all of the vital metabolic processes of the cell. In this chapter, we reviewed dietary lipids and different ways that lipids are metabolized in the cell. We also covered lipid transport in blood and lymphatic fluid and the mobilization of lipids from adipocytes. In addition, we went over the structure, synthesis, and breakdown of fatty acids required to address the energy needs of the cell. The importance of ketone bodies and how they are utilized by the cell during periods of starvation were also reviewed. Finally, we went over digestion and metabolism of proteins and amino acids.

Metabolism of the different macromolecules does not occur in isolation, as you've already seen: the acetyl-CoA produced in fatty acid oxidation regulates the pyruvate dehydrogenase complex and pyruvate carboxylase to create a shift in carbohydrate metabolism from glycolysis and the citric acid cycle to gluconeogenesis. In the next chapter, we'll dive into how the different pathways fit together and will integrate the metabolic knowledge that you've compiled in Chapters 9, 10, and 11 of MCAT Biochemistry Review.

Concept Summary

Lipid Digestion and Absorption

·        Mechanical digestion of lipids occurs primarily in the stomach.

·        Chemical digestion of lipids occurs in the small intestine and is facilitated by bilepancreatic lipasecolipase, and cholesterol esterase.

·        Digested lipids may form micelles for absorption or be absorbed directly.

·        Short-chain fatty acids are absorbed across the intestine into the blood.

·        Long-chain fatty acids are absorbed as micelles and assembled into chylomicrons for release into the lymphatic system.

Lipid Mobilization

·        Lipids are mobilized from adipocytes by hormone-sensitive lipase.

·        Lipids are mobilized from lipoproteins by lipoprotein lipase.

Lipid Transport

·        Chylomicrons are the transport mechanism for dietary triacylglycerol molecules and are transported via the lymphatic system.

·        VLDL transports newly synthesized triacylglycerol molecules from the liver to peripheral tissues in the bloodstream.

·        IDL is a VLDL remnant in transition between triacylglycerol and cholesterol transport; it picks up cholesteryl esters from HDL.

·        LDL primarily transports cholesterol for use by tissues.

·        HDL is involved in the reverse transport of cholesterol.

·        Apoproteins control interactions between lipoproteins.

Cholesterol Metabolism

·        Cholesterol may be obtained through dietary sources or through de novo synthesis in the liver.

·        The key enzyme in cholesterol biosynthesis is HMG-CoA reductase.

·        LCAT catalyzes the formation of cholesteryl esters for transport with HDL.

·        CETP catalyzes the transition of IDL to LDL by transferring cholesteryl esters from HDL.

Fatty Acids and Triacylglycerols

·        Fatty acids are carboxylic acids, typically with a single long chain, although they can be branched.

·        Saturated fatty acids have no double bonds between carbons. Unsaturated fatty acids have one or more double bonds.

·        Fatty acids are synthesized in the cytoplasm from acetyl-CoA transported out of the mitochondria.

o   Synthesis includes five steps: activation, bond formation, reduction, dehydration, and a second reduction.

o   These steps are repeated eight times to form palmitic acid, the only fatty acid that humans can synthesize.

·        Fatty acid oxidation occurs in the mitochondria following transport by the carnitine shuttle.

o   β-oxidation uses cycles of oxidation, hydration, oxidation, and cleavage.

o   Branched and unsaturated fatty acids require special enzymes.

o   Unsaturated fatty acids use an isomerase and an additional reductase during cleavage.

Ketone Bodies

·        Ketone bodies form (ketogenesis) during a prolonged starvation state due to excess acetyl-CoA in the liver.

·        Ketolysis regenerates acetyl-CoA for use as an energy source in peripheral tissues.

·        The brain can derive up to two-thirds of its energy from ketone bodies during prolonged starvation.

Protein Catabolism

·        Protein digestion occurs primarily in the small intestine.

·        Catabolism of cellular proteins occurs only under conditions of starvation.

·        Carbon skeletons of amino acids are used for energy, either through gluconeogenesis or ketone body formation. Amino groups are fed into the urea cycle for excretion. The fate of a side chain depends on its chemistry.

Answers to Concept Checks

·        11.1

1.    Physical digestion is accomplished in the mouth and the stomach, reducing the particle size. Beginning in the small intestine, pancreatic lipase, colipase, cholesterol esterase, and bile assist in the chemical digestion of lipids. In the more distal portion of the small intestine, absorption occurs.

2.    False. Small free fatty acids enter the circulation directly.

3.    Micelles are collections of lipids with their hydrophobic ends oriented toward the center and their charged ends oriented toward the aqueous environment. Micelles collect lipids within their hydrophobic centers.

·        11.2

1.    In the postabsorptive and prolonged fasting states, lipid mobilization is favored. A decrease in insulin levels, as well as an increase in epinephrine or cortisol, will increase lipid mobilization from adipocytes.

2.    The ratio of free fatty acids to glycerol is 3:1. A triacylglycerol molecule is composed of glycerol and three fatty acids.

·        11.3

1.    Free fatty acids remain in the blood, bound to albumin and other carrier proteins. A much smaller amount will remain unbound.

2.    With respect to protein content, HDL > LDL > IDL > VLDL > chylomicrons. VLDL and chylomicrons are the primary triacylglycerol transporters. HDL and LDL are mostly involved in cholesterol transport.

3.    Lipoproteins are synthesized primarily by the intestine and liver.

·        11.4

1.    HMG-CoA reductase is most active in the absence of cholesterol and when stimulated by insulin. Cholesterol reduces the activity of HMG-CoA reductase, which is located in the smooth endoplasmic reticulum.

2.    LCAT catalyzes the esterification of cholesterol to form cholesteryl esters. CETP promotes the transfer of cholesteryl esters from HDL to IDL, forming LDL.

·        11.5

1.    Palmitic acid (16:0):

α-linolenic acid (18:3 all-cis-9,12,15), an ω-3 fatty acid:

Linoleic acid (18:2 cis,cis-9,12), an ω-6 fatty acid:

Note: as long as the last double bond is in the same position relative to the end of the chain, many answers are possible for the ω-6 fatty acid.

2.    The steps in the attachment of acetyl-CoA to a fatty acid chain are attachment to acyl carrier protein, bond formation between molecules, reduction of a carboxyl group, dehydration, and reduction of a double bond. These steps are shown in Figure 11.6.

3.    There is an additional isomerase and an additional reductase for the β-oxidation of unsaturated fatty acids, which provide the stereochemistry necessary for further oxidation.

4.    True.

11.6

1.    Fatty acid degradation results in large amounts of acetyl-CoA, which cannot enter the gluconeogenic pathway to produce glucose. Only odd-numbered fatty acids can act as a source of carbon for gluconeogenesis; even then, only the final malonyl-CoA molecule can be used. Energy is packaged into ketone bodies for consumption by the brain and muscles.

2.    Ketogenesis is favored by a prolonged fast and occurs in the liver. It is stimulated by increasing concentrations of acetyl-CoA. Ketolysis is also favored during a prolonged fast, but is stimulated by a low-energy state in muscle and brain tissues and does not occur in the liver.

11.7

1.    False. Proteins are more valuable to the cell than lipids, thus they will not commonly be broken down for lipid synthesis.

2.    The bulk of protein digestion occurs in the small intestine.

3.    The carbon skeleton is transported to the liver for processing into glucose or ketone bodies. The amino group will feed into the urea cycle for excretion. Side chains are processed depending on their composition. Basic side chains will be processed like amino groups, while other functional groups will be treated like the carbon skeleton.

Shared Concepts

·        Biochemistry Chapter 1

o   Amino Acids, Peptides, and Proteins

·        Biochemistry Chapter 5

o   Lipid Structure and Function

·        Biochemistry Chapter 8

o   Biological Membranes

·        Biochemistry Chapter 12

o   Bioenergetics and Regulation of Metabolism

·        Biology Chapter 9

o   The Digestive System

·        Biology Chapter 10

o   Homeostasis