1 Chapter 24 Metabolic Pathways for Lipids and Amino Acids 24.1 Digestion of Triacylglycerols Copyright © 2007 by Pearson Education, Inc. Publishing as.

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Chapter 24 Metabolic Pathways for Lipids and Amino Acids

24.1Digestion of Triacylglycerols

Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings

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Digestion of Fats (Triacylglycerols)In the digestion of fats (triacylglycerols),

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.

Fatty acids bind with proteins forming lipoproteins to transport triacylglycerols to the cells of the heart, muscle, and adipose tissues.

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Digestion of Triacylglycerols


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Fat Mobilization

Fat mobilization Breaks down

triacylglycerols in adipose tissue.

Forms fatty acids and glycerol.

Hydrolyzes fatty acid initially from C1 or C3 of the fat.

triacylglycerols + 3 H2O glycerol + 3 fatty acids


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Metabolism of Glycerol

Glycerol from fat digestion Adds a phosphate from ATP to form glycerol-3-

phosphate. Undergoes oxidation of the –OH group to

dihydroxyacetone phosphate. Becomes an intermediate used in glycolysis and

gluconeogenesis.

Glycerol + ATP + NAD+

dihydroxyacetone phosphate + ADP + NADH + H+

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Oxidation of Glycerol

OHH2C

OHC

H2C OH

OHH2C

OHC

H2C

ATP

O P O-

O

O-

ADP

OHH2C

OC

H2C O P O-

O

O-

glycerol glycerol-3-phosphate

dihydroxyacetone phosphate

glycolysis gluconeogenesis

NAD+

NADH + H+

glyerol kinase

dehydrogenase

+ +

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Learning Check

Give answers for the following questions on fat

digestion.

1. What is the function of bile salts in fat digestion?

2. Why are the triacylglycerols in the intestinal lining

coated with proteins to form chylomicrons?

3. How is glycerol utilized?

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Solution

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. Why are the triacylglycerols in the intestinal lining

coated with proteins to form chylomicrons? The proteins coat the triacylglycerols to make water soluble chylomicrons that move into the lymph and bloodstream. 3. How is glycerol utilized? Glycerol adds a phosphate and is oxidized to an intermediate of the glycolysis and gluconeogenesis pathways.

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24.2

Oxidation of Fatty acids

24.3

ATP and Fatty Acid Oxidation


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Fatty Acid Activation

Fatty acid activation Allows the fatty acids in the cytosol to enter the

mitochondria for oxidation. Combines a fatty acid with CoA to yield fatty acyl

CoA that combines with carnitine.


Fatty acyl

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Transport of Fatty Acyl CoA

Fatty acyl-CoA forms fatty acyl-carnitine that transports the fatty acyl group into the matrix.

The fatty acyl group recombines with CoA for oxidation.


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Summary of Fatty Acid Activation

Fatty acid activation is complex, but it regulates the degradation and synthesis of fatty acids.


Fatty acyl

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Beta-Oxidation of Fatty Acids

Fatty acyl CoA undergoes

β oxidation in a cycle of four

reactions.

In reaction 1, oxidation

Removes H atoms from the and carbons.

Forms a trans C=C bond.

Reduces FAD to FADH2.


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In reaction 2 of

β oxidation, hydration

Adds water across the trans C=C bond.

Forms a hydroxyl group (—OH) on the carbon.


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In reaction 3 of β

oxidation, a second

oxidation Oxidizes the

hydroxyl group. Forms a keto

group on the carbon.


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Beta()-Oxidation of Fatty Acids

In Reaction 4 of β-

oxidation, acetyl CoA

is cleaved By splitting the bond

between the and carbons.

To form a shortened fatty acyl CoA that repeats steps 1 - 4 of -oxidation.


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Learning Check

Match the reactions of -oxidation with each:

1) oxidation 1 2) hydration

3) oxidation 2 4) acetyl CoA cleaved

A. Water is added.

B. FADH2 forms.

C. A two-carbon unit is removed.

D. A hydroxyl group is oxidized.

E. NADH forms.

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Solution

Match the reactions of -oxidation with each:1) oxidation 1 2) hydration3) oxidation 2 4) acetyl CoA cleaved

A. 2 Water is added.B. 1 FADH2 forms. C. 4 A two-carbon unit is removed.D. 3 A hydroxyl group is oxidized.E. 3 NADH forms.

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Beta()-Oxidation of Myristic (C14) Acid


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Beta()-Oxidation of Myristic (C14) Acid (continued)

7 Acetyl CoA

6 cycles

C14

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Fatty Acid Length and -OxidationThe length of a fatty acid Determines the number of oxidations Determines the total number of acetyl CoA groups.

Carbons in Acetyl CoA -Oxidation Cycles

Fatty Acid (#C/2) (#C/2 –1)

12 6 5

14 7 6

16 8 7

18 9 8

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Learning Check

A. The number of acetyl CoA groups produced by the complete -oxidation of palmitic acid (C16 ):

1) 16 2) 8 3) 7

B. The number of oxidation cycles to completely oxidize palmitic acid (C16 ):

1) 16 2) 8 3) 7

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Solution

A. The number of acetyl CoA groups produced by the complete -oxidation of palmitic acid (C16 ):

2) 8 (16 C/2 = 8)

B. The number of oxidation cycles to completely oxidize palmitic acid (C16 ):

3) 7 (16 C/2 -1 = 7)

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ATP and -Oxidation

Activation of a fatty acid requires

2 ATP

One cycle of oxidation of a fatty acid produces

1 NADH 3 ATP

1 FADH2 2 ATP

Acetyl CoA entering the citric acid cycle produces

1 Acetyl CoA 12 ATP

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ATP for Lauric Acid C12

ATP production for lauric acid (12 carbons):

Activation of lauric acid -2 ATP

6 Acetyl CoA

6 acetyl CoA x 12 ATP/acetyl CoA 72 ATP

5 Oxidation cycles

5 NADH x 3ATP/NADH 15 ATP

5 FADH2 x 2ATP/FADH2 10 ATP

Total 95 ATP

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Learning Check

The total ATP produced from the -oxidation of stearic acid (C18) is

1) 108 ATP

2) 146 ATP

3) 148 ATP

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Solution

The total ATP produced from the -oxidation of stearic acid (C18) is:

2) 146 ATP

Activation -2 ATP

9 Acetyl CoA x 12 ATP 108 ATP

8 NADH x 3 ATP 24 ATP

8 FADH2 x 2 ATP 16 ATP

146 ATP

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24.4

Ketogenesis and Ketone Bodies



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Ketogenesis

In ketogenesis

Large amounts of acetyl CoA accumulate.

Two acetyl CoA molecules combine to form acetoacetyl CoA.

Acetoacetyl CoA hydrolyzes to acetoacetate, a ketone body.

Acetoacetate reduces to -hydroxybutyrate or loses CO2 to form acetone, both ketone bodies.

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Reactions of Ketogenesis

Ketone bodies


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Ketosis

Ketosis occurs In diabetes, diets high

in fat, and starvation. As ketone bodies

accumulate. When acidic ketone

bodies lowers blood pH below 7.4 (acidosis). Copyright © 2007 by Pearson Education, Inc.

Publishing as Benjamin Cummings

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Ketone Bodies and Diabetes

In diabetes Insulin does not

function property. Glucose levels are

insufficient for energy needs.

Fats are broken down to acetyl CoA.

Ketogenesis produces ketone bodies.


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Learning Check

In ketogenesis, match the type of reaction with

1) oxidation 2) reduction 3) decarboxylation

A. acetoacetate produces acetone

B. acetoacetate produces β-hydroxybutyrate

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Solution

In ketogenesis, match the type of reaction with

1) oxidation 2) reduction 3) decarboxylation

A. acetoacetate produces acetone 3

B. acetoacetate produces β-hydroxybutyrate 2

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24.5

Fatty Acid Synthesis


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Lipogenesis: Fatty Acid Synthesis

Lipogenesis Is the synthesis of fatty acids from acetyl CoA. Occurs in the cytosol. Uses reduced coenzyme NADPH (NADH with a

phosphate group). Requires an acyl carrier protein (ACP).


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Synthesis of Malonyl CoA

For fatty acid synthesis, Acetyl CoA combines with bicarbonate to form

malonyl CoA. ATP hydrolysis provides energy. O acetyl CoA

|| carboxylase

CH3—C—S—CoA + HCO3- + ATP

acetyl CoA

O O || ||

-O—C—CH2—C—S—CoA + ADP + Pi + H+

malonyl CoA

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Acetyl and Malonyl Acyl Carrier Proteins (ACP)

Active forms of acetyl ACP and malonyl-ACP are

produced by combining with acyl carrier proteins (ACP). O O

║ ║CH3—C—S—CoA + HS-ACP CH3—C—S—ACP + HS-CoA acetyl-ACP

O O || ||

-O—C—CH2—C—S—CoA + HS-ACP O O || ||

-O—C—CH2—C—S—ACP + HS-CoAmalonyl-ACP

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Fatty Acid Synthesis: Condensation and Reduction

In reactions 1 and 2 of fatty

acid synthesis Condensation (1) by a

synthase combines acetyl-ACP with malonyl-ACP to form acetoacetyl-ACP (4C) and CO2.

Reduction(2) converts a ketone to an alcohol using NADPH.

Copyright © 2007 by Pearson Education, Inc.Publishing as Benjamin Cummings

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Fatty Acid Synthesis: Dehydration and Reduction

In reactions 3 and 4 of

fatty acid synthesis Dehydration(3) forms a

trans double bond. Reduction (4) converts

the double bond to a single bond using NADPH.


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Fatty Acid Synthesis (Lipogenesis) Cycle Repeats

Fatty acid synthesis

continues as Malonyl-ACP

combines with the four-carbon butyryl-ACP to form a six-carbon-ACP.

The carbon chain lengthens by two carbons each cycle.


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Fatty Acid Synthesis (Lipogenesis) Cycle Completed

Fatty acid synthesis

Is completed when palmitoyl ACP reacts with water to give palmitate (C16) and free ACP.


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Summary of Lipogenesis


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Fatty Acid Length

In fatty acid synthesis Shorter fatty acids undergo fewer cycles. Longer fatty acids are produced from palmitate using

special enzymes. Unsaturated cis bonds are incorporated into a 10-

carbon fatty acid that is elongated further.

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Regulation of Fatty Acid Synthesis

In fatty acid synthesis A high level of blood glucose and insulin stimulates

glycolysis and pyruvate oxidation. More acetyl CoA is available to form fatty acids.

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Comparing -Oxidation and Fatty Acid Synthesis


TABLE 24.1

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Learning Check

Match each with the description below:1) mitochondria 2) cytosol3) glucagon 4) insulin5) acetyl ACP 6) malonyl ACP

A. Site of fatty acid synthesis.B. Site of -oxidation.C. Starting material for lipogenesis.D. Compound added to elongate acyl-ACP.E. Activates -oxidation.F. Activates lipogenesis.

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Solution

Match each with the description below:1) mitochondria 2) cytosol3) glucagon 4) insulin5) acetyl ACP 6) malonyl ACP

A. 2 Site of fatty acid synthesis.B. 1 Site of -oxidation.C. 5,6 Starting material for lipogenesis.D. 6 Compound added to elongate acyl-ACP.E. 3 Activates -oxidation.F. 4 Activates lipogenesis.

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24.6

Digestion of Proteins

24.7

Degradation of Amino Acids


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The digestion of proteins (stage 1) Begins in the stomach where HCl in stomach acid

activates pepsin to hydrolyze peptide bonds.

Continues in the small intestine where trypsin and chymotrypsin hydrolyze peptides to amino acids.

Is complete as amino acids enter the bloodstream for transport to cells.

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Learning Check

Match the end products of digestion with the types of

food:

1. amino acids 2. fatty acids and glycerol

3. glucose

A. fats

B. proteins

C. carbohydrates

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Solution

Match the end products of digestion with the types of

food:

1. amino acids 2. fatty acids and glycerol

3. glucose

A. fats 2. fatty acids and glycerol

B. proteins 1. amino acids

C. carbohydrates 3. glucose

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Proteins in the Body

Proteins provide Amino acids for

protein synthesis. Nitrogen atoms for

nitrogen-containing compounds.

Energy when carbohydrate and lipid resources are not available.


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Transamination

In transamination Amino acids are degraded in the liver. An amino group is transferred from an amino acid

to an -keto acid, usually -ketoglutarate. The reaction is catalyzed by a transaminase or

aminotransferase. A new amino acid, usually glutamate, and a new

-keto acid are formed.

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A Transamination Reaction

NH3+ O alanine

| || aminotransferase

CH3—CH—COO- + -OOC—C—CH2—CH2—COO-

alanine -ketoglutarate

O NH3+

|| |CH3—C—COO- + -OOC—CH—CH2—CH2—COO-

pyruvate glutamate

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Oxidative Deamination

Oxidative deamination Removes the amino group as an ammonium ion from

glutamate. Provides -ketoglutarate for transamination. NH3

+ glutamate | dehydrogenase-OOC—CH—CH2—CH2—COO- + NAD+ + H2O glutamate

O || -OOC—C—CH2—CH2—COO- + NH4

+ + NADH -ketoglutarate

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Learning Check

Write the products from the transamination of

-ketoglutarate by aspartate.

NH3+

|-OOC—CH—CH2—COO-

aspartate O || -OOC—C—CH2—CH2—COO-

-ketoglutarate

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Solution

Write the products from the transamination of -ketoglutarate by aspartate. O

|| -OOC—C—CH2—COO-

oxaloacetate

NH3+

| -OOC—CH—CH2—CH2—COO-

glutamate

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24.8

Urea Cycle


O ||

H2N—C—NH2 urea

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Urea Cycle

The urea cycle Detoxifies ammonium ion from amino acid

degradation.

Converts ammonium ion to urea in the liver.

O ||

H2N—C—NH2 urea

Provides 25-30 g urea daily for urine formation in the kidneys.

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Carbamoyl Phosphate

Carbamoyl phosphate is formed In the mitochondria, when ammonium ion reacts with

CO2 from the citric acid cycle, 2 ATP, and water.carbomyl phosphate

synthetase

NH4+ + CO2 + 2ATP + H2O

O O || ||H2N—C—O—P—O- + 2ADP + Pi

|O-

carbamoyl phosphate

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Reaction 1 Transfer of Carbamoyl GroupIn reaction 1 of the urea cycle, The carbamoyl group is transferred to ornithine to

form citrulline. Citrulline moves across the mitochondrial

membrane into the cytosol.


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Reaction 2 Condensation with Aspartate

In reaction 2 of the urea

cycle, That takes place in the

cytosol, citrulline combines with aspartate.

Hydrolysis of ATP to AMP provides energy.

The N in aspartate is part of urea.

Cytosol


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Reaction 3 Cleavage of Fumarate

In reaction 3 of the urea cycle, fumarate Is cleaved from argininosuccinate. Enters the citric acid cycle.


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Reaction 4 Hydrolysis Forms Urea

In reaction 4 of the urea

cycle, Arginine is hydrolyzed Urea forms. Ornithine returns to the

mitochondrion to pick up another carbamoyl group to repeat the urea cycle.


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Urea Cycle


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Summary of Urea Cycle

The urea cycle converts: Ammonium ion to urea Aspartate to Fumarate 3ATP to 2ADP, AMP, 4Pi

NH4+ + CO2 + 3ATP + aspartate + 2H2O

urea + 2ADP + AMP + 4Pi + fumarate

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Learning Check

Identify the site for each as:

1) mitochondrion 2) cytosol

A. Formation of urea.

B. Formation of carbamoyl phosphate.

C. Aspartate combines with citrulline.

D. Fumarate is cleaved.

E. Citrulline forms.

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Solution

Identify the site for each as:

1) mitochondrion 2) cytosol

A. 2 Formation of urea.

B. 1 Formation of carbamoyl phosphate.

C. 2 Aspartate combines with citrulline.

D. 2 Fumarate is cleaved.

E. 1 Citrulline forms.

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24.9 Fates of the Carbon Atoms from

Amino Acids



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Carbon Atoms from Amino Acids

When needed, carbon skeletons of amino acids are used

to produce energy by forming intermediates of the citric

acid cycle.

Three-carbon skeletons alanine, serine, and cysteine pyruvate

Four-carbon skeletons aspartate, asparagine oxaloacetate

Five-carbon skeletons glutamine, glutamate, proline,

arginine, histidine glutamate

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Glucogenic and Ketogenic Amino Acids

Amino acids are classified as

Glucogenic if they generate pyruvate or oxaloacete, which can be used to synthesize glucose.

Ketogenic if they generate acetoacetyl CoA or acetyl CoA, which can form ketone bodies or fatty acids.

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Ketogenic

Glucogenic


Amino Acid Pathways to Citric Acid Intermediates

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Amino Acid Pathways to Pyruvate and Oxaloacetate


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Glucogenic Amino Acids that Form Intermediates of the Citric Acid Cycle


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Learning Check

Match each the intermediate with the amino acid that

provides its carbon skeleton.

1) pyruvate 2) fumarate 3) -ketoglutarate

A. cysteine

B. glutamine

C. aspartate

D. serine

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Solution

Match each the intermediate with the amino acid that

provides its carbon skeleton.

1) pyruvate 2) fumarate 3) -ketoglutarate

A. 1 cysteine

B. 3 glutamine

C. 2 aspartate

D. 1 serine

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Learning Check

Identify each as glucogenic (G) or ketogenic (K)

A. alanine

B. lysine

C. phenylalanine

D. aspartate

E. glutamate

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Solution

Identify each as glucogenic (G) or ketogenic (K)

A. G alanine

B. K lysine

C. K phenylalanine

D. G aspartate

E. G glutamate

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24.10

Synthesis of Amino Acids



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Sources of Amino Acids

Essential amino acids must be obtained in the diet. Nonessential amino acids are synthesized in the

body. TABLE 24.3


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Synthesis of Amino Acids

In humans, transamination of compounds from glycolysis or the citric acid cycle produces nonessential amino acids.


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Synthesis of Glutamine

Glutamine is synthesized by adding another amino group to glutamate.

NH3

+ glutamine

| synthetase-OOC—CH—CH2—CH2—COO- + NH3 + ATP

glutamate

NH3+ O

| ||-OOC—CH—CH2—CH2—C—NH2 + ADP + Pi

glutamine

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Learning Check

Match each amino acid with the intermediate needed for

its synthesis:

1) alanine 2) glutamate 3) aspartate

A. pyruvate

B. oxaloacetate

C. -ketoglutarate

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Solution

Match each amino acid with the intermediate needed for

its synthesis:

1) alanine 2) glutamate 3) aspartate

A. 1 pyruvate

B. 3 oxaloacetate

C. 2 -ketoglutarate

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Phenylketonurea (PKU)

In phenylketonurea (PKU) The gene that converts phenylalanine to tyrosine is

defective. Phenylalanine forms phenylpyruvate

(transamination), which goes to phenylacetate (decarboxylation).

High levels of phenylacetate cause severe mental retardation.

A diet low in phenylalanine and high in tyrosine is recommended.

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Phenylketonurea (PKU)


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Overview of Metabolism

In metabolism Catabolic pathways degrade large molecules. Anabolic pathway synthesize molecules. Branch points determine which compounds are

degraded to acetyl CoA to meet energy needs or converted to glycogen for storage.

Excess glucose is converted to body fat. Fatty acids and amino acids are used for energy

when carbohydrates are not available. Some amino acids are produced by transamination.

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1 Chapter 24 Metabolic Pathways for Lipids and Amino Acids 24.1 Digestion of Triacylglycerols Copyright © 2007 by Pearson Education, Inc. Publishing as.

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