General orrganic and biological chemistry structures off liffe 5th CH 24 digestion triacylglycerols GOB structures 5th ed

Lecture Presentation

Chapter 24

Metabolic Pathways for Lipids
and
Amino Acids

Karen C. Timberlake

General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake

© 2016 Pearson Education, Inc.


Chapter 24 Metabolic Pathways for Lipids and Amino Acids

Patients diagnosed with chronic hepatitis C virus
(HCV) infection require lifelong monitoring by a
specialist team including a public health nurse.
A public health nurse works in public health
departments, correctional facilities, occupational
health facilities, schools, and organizations that aim
to improve health at the community level.

General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake

© 2016 Pearson Education, Inc.

Chapter 24 Readiness

Core Chemistry Skills

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Identifying Fatty Acids (17.2)
Drawing the Zwitterion for an Amino Acid (19.1)
Identifying Important Coenzymes in Metabolism (22.3)
Identifying the Compounds in Glycolysis (22.4)
Identifying the Compounds and Enzymes in Glycogenesis and Glycogenolysis (22.6)
Describing the Reactions in the Citric Acid Cycle (23.1)
Calculating the ATP Produced from Glucose (23.3)

General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake

© 2016 Pearson Education, Inc.


24.1 Digestion of Triacylglycerols

The fat cells (adipocytes) that make up adipose tissue are capable of storing unlimited quantities of

triacylglycerols.
Adipose tissue (made of adipocytes) stores 85% of the total energy available in the body.

Learning Goal Describe the sites of and products obtained from the digestion of triacylglycerols.

General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake

© 2016 Pearson Education, Inc.


Digestion of Triacylglycerols

In the digestion of fats (triacylglycerols),

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bile salts break fat globules into smaller particles called micelles in the small intestine.
pancreatic lipases hydrolyze ester bonds to form monoacylglycerols and fatty acids, which recombine in
the intestinal lining.

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phospholipids and proteins coat the fats, forming chylomicrons, which are transported to the cells of
heart, muscle, and adipose tissues.

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lipases hydrolyze triacylglycerols, forming glycerol and free fatty acids, which are oxidized to acetyl CoA

molecules for ATP synthesis.

General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake

© 2016 Pearson Education, Inc.


Digestion of Triacylglycerols

The digestion of fats begins in the small intestine when bile salts emulsify fats that undergo hydrolysis to
monoacylglycerols and fatty acids.

General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake

© 2016 Pearson Education, Inc.


Utilization of Fat

When blood glucose is depleted and glycogen stores are low,

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the process of fat utilization is stimulated.
the hormones glucagon or epinephrine are secreted into the bloodstream, where they bind to
receptors on the membrane of adipose tissue.

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a hormone-sensitive lipase within the fat cells catalyzes the hydrolysis of triacylglycerols to glycerol
and free
fatty acids.

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glycerol and fatty acids diffuse into the bloodstream and bind with plasma proteins to be transported
to the tissues, muscles, and fat cells.

General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake

© 2016 Pearson Education, Inc.


Metabolism of Glycerol

Glycerol from fat digestion

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adds a phosphate from ATP to form
glycerol-3-phosphate.

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undergoes oxidation of the —OH group to dihydroxyacetone phosphate.

becomes an intermediate in glycolysis and gluconeogenesis.

General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake

© 2016 Pearson Education, Inc.


Metabolism of Glycerol

General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake

© 2016 Pearson Education, Inc.


Study Check

Give answers for the following questions about fat digestion:
1. What is the function of bile salts in fat digestion?

2. How is glycerol utilized?

General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake

© 2016 Pearson Education, Inc.


Solution

Give answers for the following questions about fat digestion:
1.

What is the function of bile salts in fat digestion?

Bile salts break down fat globules, allowing pancreatic lipases to hydrolyze the
triacylglycerol.

2.

How is glycerol utilized?

Glycerol adds a phosphate and is oxidized to an intermediate of the glycolysis and
gluconeogenesis pathways.

General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake

© 2016 Pearson Education, Inc.


General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake

© 2016 Pearson Education, Inc.


24.2 Oxidation of Fatty Acids

A large amount of energy is obtained when fatty acids undergo

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oxidation in the mitochondria to acetyl CoA.
beta oxidation, (β oxidation) which removes two-carbon segments containing the alpha and beta carbon
from the carboxyl end of the fatty acid.

Learning Goal Describe the metabolic pathway of β oxidation.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake

© 2016 Pearson Education, Inc.


β Oxidation

A cycle in β oxidation

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produces an acetyl CoA and a fatty acid that is shorter by two carbons.
repeats until the original fatty acid is completely degraded to two-carbon units that form
acetyl CoA, which enters the citric acid cycle.

General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake

© 2016 Pearson Education, Inc.


Fatty Acid Activation

Fatty acids in the cytosol are transported through the inner mitochondrial membrane to undergo β oxidation
in the matrix.
In an activation process,

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a fatty acid is combined with CoA to yield a high-energy fatty acyl CoA.
energy is released by the hydrolysis of ATP to AMP and used to drive the reaction.

General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake

© 2016 Pearson Education, Inc.


Transport of Fatty Acyl CoA

A transport system called the carnitine shuttle carries fatty acids into the mitochondria from the cytosol.

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Carnitine acyltransferase catalyzes the transfer of a fatty acyl group to the hydroxyl group of
carnitine to produce fatty acyl carnitine.

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Fatty acyl carnitine then passes through the inner mitochondrial membrane into the matrix.

General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake

© 2016 Pearson Education, Inc.


Transport of Fatty Acyl CoA

General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake

© 2016 Pearson Education, Inc.


Transport of Fatty Acyl CoA

In the matrix, another carnitine acyltransferase

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catalyzes the reverse reaction that transfers the fatty acyl group to CoA to reform fatty
acyl CoA.

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releases the carnitine and returns to the cytosol.

Thus, the carnitine shuttle moves fatty acyl CoA from the cytosol into the matrix, where the
fatty acid can undergo β oxidation.

General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake

© 2016 Pearson Education, Inc.


Carnitine Shuttle System

In the carnitine shuttle system, fatty acids are activated and transported from the cytosol
through the inner mitochondrial membrane into the matrix.

General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake

© 2016 Pearson Education, Inc.


Beta (β) Oxidation of Fatty Acids:
Reaction 1

Fatty acyl CoA undergoes beta (β) oxidation in a cycle of four reactions.
In reaction 1,

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acyl CoA dehydrogenase catalyzes the transfer of hydrogen atoms from the α and β carbons of the

activated fatty acid.

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a trans C = C bond is formed between α and β carbons, and the reduced coenzyme FADH 2 is
produced.

General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake

© 2016 Pearson Education, Inc.


Beta (β) Oxidation of Fatty Acids:
Reaction 2

In reaction 2,

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a hydration reaction catalyzed by enoyl CoA hydratase adds the components of water to the trans
double bond.

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a hydroxyl group (—OH) attaches to the β carbon of the fatty acid, and a hydrogen atom attaches to the
α carbon.

General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake

© 2016 Pearson Education, Inc.


Beta (β) Oxidation of Fatty Acids:
Reaction 3

In reaction 3,

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the secondary hydroxyl group on the β carbon (carbon 3)
is oxidized by 3-hydroxyacyl CoA dehydrogenase to yield
a ketone.

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+
the hydrogen atoms removed in the oxidation are transferred to NAD to yield a β keto or 3-keto group
and the reduced coenzyme NADH.

General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake

© 2016 Pearson Education, Inc.


Beta (β) Oxidation of Fatty Acids:
Reaction 4

In reaction 4,

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the Cα — Cβ bond is cleaved by β-ketoacyl CoA thiolase to yield a two-carbon acetyl CoA and a new fatty acyl
CoA that is shortened by two carbon atoms.

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the shorter fatty acyl CoA repeats the four steps of the β- oxidation cycle until the original fatty acid is completely
degraded to two-carbon units of acetyl CoA.

General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake

© 2016 Pearson Education, Inc.


Fatty Acid Length Determines Cycle Repeats

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The number of carbons in a fatty acid determines the number of times the cycle repeats and the
number of acetyl-CoA units it produces.

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The total number of times the cycle repeats is one fewer than the total number of acetyl groups it
produces.

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Odd-numbered fatty acids go through the same four steps of β oxidation until the final cycle, in which
the remaining fatty acyl CoA is cleaved to yield a propionyl CoA (C 3) group and an acetyl CoA.

General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake

© 2016 Pearson Education, Inc.


Beta (β) Oxidation of Fatty Acids

Capric acid (C10) undergoes four oxidation
cycles that repeat reactions 1 to 4 and yield five
acetyl CoA molecules, four NADH, and four
FADH2.

General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake

© 2016 Pearson Education, Inc.