Quiz 10- (Final)

Fatty acids are stored in adipose tissue as

triacylglycerols (TAG) in which fatty acids are linked to glycerol with ester linkages

Adipose tissue

located throughout the body, with subcutaneous (below the skin) and visceral (around the internal organs) deposits being most prominent

Fatty acids are stored in adipose tissue as

triacylglycerols (TAG) in which fatty acids are linked to glycerol with ester linkages

Adipose tissue

located throughout the body, with subcutaneous (below the skin) and visceral (around the internal organs) deposits being most prominent

The fatty acids incorporated into triacylglycerols in adipose tissue are made accessible in three stages

1.Degradation of TAG to release fatty acids and glycerol into the blood for transport to energy-requiring tissues

2.Activation of the fatty acids and transport into the mitochondria for oxidation

3.Degradation of the fatty acids to acetyl CoA for processing by the citric acid cycle

Lipid Degradation

Lipids are hydrolyzed by lipases in three steps to yield fatty acids and glycerol. The fatty acids are taken up by cells and used as a fuel. Glycerol also enters the liver, where it can be metabolized by the glycolytic or gluconeogenic pathways.

Triacylglycerols are stored in adipocytes as

a lipid droplet

Epinephrine and glucagon stimulate

lipid breakdown or lipolysis through 7TM receptors

Protein kinase A phosphorylates

perilipin, which is associated with the lipid droplet, and hormone-sensitive lipase.

Phosphorylation of perilipin results in

the activation of adipocyte triacylglyceride lipase (ATGL).

Rearrangement of the lipid molecule releases a

coactivator of ATGL.

ATGL initiates

breakdown of lipids

Chanarin-Dorfmam syndrome results if

ATGL activity is compromised

Triacylglycerols in Adipose Tissue are Converted into Free Fatty Acids in Response to

Hormonal Signals

Figure 27.2 

The phosphorylation of perilipin restructures the lipid droplet and releases the coactivator of ATGL. The activation of ATGL by binding with its coactivator initiates the mobilization. Hormone-sensitive lipase releases a fatty acid from diacylglycerol. Monoacylglycerol lipase completes the mobilization process. Abbreviations: 7TM, seven transmembrane; ATGL, adipose triglyceride lipase; CA, coactivator; HS lipase, hormone-sensitive lipase; MAG lipase, monoacylglycerol lipase; DAG, diacylglycerol; TAG, triacylglycerol

fatty acids are not

soluble in aqueous solutions, they bind to the blood protein albumin, which delivers them to tissues in need of fuel.

The glycerol released during lipolysis is absorbed by

the liver for use in glycolysis or gluconeogenesis.

Upon entering the cell cytoplasm, fatty acids are activated by

attachment to coenzyme A

Fatty acids are linked to

coenzyme A before they are oxidized.

Linking a fatty acid to coenzyme A is

a  two-step reaction that proceeds through an acyl adenylate intermediate.

The fatty acid reacts with ATP to form

an acyl adenylate, and the other two phosphoryl groups of the ATP substrate are released as pyrophosphate

The sulfhydryl group of CoA then attacks the acyl adenylate to form

acyl CoA and AMP.

Fatty acids are linked to

coenzyme A before they are oxidized.

The reaction is rendered irreversible by

The reaction is rendered irreversible by

After being activated by linkage to CoA, the fatty acid is transferred to

carnitine for transport across the inner mitochondrial membrane

carnitine

a reaction catalyzed by carnitine acyltransferase I,

A translocase transports the acyl carnitine into

the matrix of the mitochondria.

In the mitochondria, carnitine acyltransferase II transfers the fatty acid to

CoA

Acyl carnitine translocase

The entry of acyl carnitine into the mitochondrial matrix is mediated by a translocase. Carnitine returns to the cytoplasmic side of the inner mitochondrial membrane in exchange for acyl carnitine.

Muscle, kidney, and heart use

fatty acids as a fuel

Pathological conditions result if

the acyltransferase or the translocase is deficient.

Fatty acid degradetion consists of four steps that are repeated. name thaw

1.Oxidation of the β carbon, catalyzed by acyl CoA dehydrogenase, generates trans-Δ2-enoyl CoA and FADH2.

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2.Hydration of trans-Δ2-enoyl CoA by enoyl CoA hydratase yields l-3-hydroxyacyl CoA

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3.Oxidation of l-3-hydroxyacyl CoA by l-3-hydroxyacyl CoA dehydrogenase generates 3-ketoacyl CoA and NADH.

4.Cleavage of the 3-ketoacyl CoA by β-ketothiolase forms acetyl CoA and a fatty acid chain two carbons shorter.

Fatty acid degradation is also called

β oxidation

What is The reaction sequence for the degradation of fatty acids

Fatty acids are degraded by the repetition of a four-reaction sequence consisting of oxidation, hydration, oxidation, and thiolysis

The first three rounds in the degradation of palmitate.

Two carbon units are sequentially removed from the carboxyl end of the fatty acid.

Principal Reactions Required for Fatty Acid Degradation

The reaction for one round of β oxidation is

The complete reaction for C16 palmitoyl CoA is

Processing of the products of the complete reaction by cellular respiration would generate

108 molecules of ATP, or net 106 molecules of ATP

Describe the repetitive steps of β oxidation. Why is the process called β oxidation?

An isomerase and a reductase are required for the oxidation of

unsaturated fatty acids

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•β oxidation alone cannot degrade unsaturated fatty acids. When monounsaturated fatty acids such as palmitoleate are degraded by β oxidation, cis-Δ3-enoyl CoA is formed, which cannot be processed by acyl CoA dehydrogenase.

Cis-Δ3-enoyl CoA isomerase converts the double bond into

trans-Δ2-enoyl CoA, a normal substrate for β oxidation.

When polyunsaturated fatty acids are degraded by βoxidation what is required?

•cis-Δ3-enoyl CoA isomerase is also required.  2,4-Dienoyl CoA is also generated but cannot be processed by the normal enzymes.

2,4-Dienoyl CoA is converted into trans-Δ3-enoyl CoA by

2,4-dienoyl CoA reductase, and the isomerase converts this product to trans-Δ2-enoyl CoA, a normal substrate

Unsaturated fatty acids with odd-numbered double bonds require only

the isomerase

Even-numbered double bonds require

both the isomerase and reductase

The oxidation of linoleoyl CoA

The complete oxidation of the diunsaturated fatty acid linoleate is facilitated by the activity of enoyl CoA isomerase and 2,4-dienoyl CoA reductase.

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β Oxidation of fatty acids with odd numbers of carbons generates

propionyl CoA in the last thiolysis reaction

Propionyl CoA carboxylase, a biotin enzyme, adds

a carbon to propionyl CoA to form methylmalonyl CoA

Succinyl CoA, a citric acid cycle component, is subsequently formed from

methylmalonyl CoA by methylmalonyl CoA mutase, a vitamin B12-requiring enzyme.

The conversion of propionyl CoA into succinyl CoA

Propionyl CoA, generated from fatty acids having an odd number of carbon atoms as well as from some amino acids, is converted into the citric acid cycle intermediate succinyl CoA

An isomerase and a reductase are required for the

oxidation of unsaturated fatty acids.

When monounsaturated fatty acids such as palmitoleate are degraded by β oxidation…. what happens?

cis-Δ3-enoyl CoA is formed, which cannot be processed by acyl CoA dehydrogenase

When polyunsaturated fatty acids are degraded by βoxidation.. what happens

cis-Δ3-enoyl CoA isomerase is also required.  2,4-Dienoyl CoA is also generated but cannot be processed by the normal enzymes.

2,4-Dienoyl CoA is converted into trans-Δ3-enoyl CoA by

2,4-dienoyl CoA reductase, and the isomerase converts this product to trans-Δ2-enoyl CoA, a normal substrate

Unsaturated fatty acids with odd-numbered double bonds require

only the isomerase

Even-numbered double bonds require

both the isomerase and reductase

The oxidation of linoleoyl CoA

The complete oxidation of the diunsaturated fatty acid linoleate is facilitated by the activity of enoyl CoA isomerase and 2,4-dienoyl CoA reductase

β Oxidation of fatty acids with odd numbers of carbons generates

propionyl CoA in the last thiolysis reaction

Propionyl CoA carboxylase, a biotin enzyme, adds a carbon to

propionyl CoA to form methylmalonyl CoA

Succinyl CoA, a citric acid cycle component, is subsequently formed from methylmalonyl CoA by

methylmalonyl CoA mutase, a vitamin B12-requiring enzyme.

Ketone-body synthesis takes place in

the liver

Ketone-body synthesis mechanism

•Ketone bodies—acetoacetate, D-3-hydroxybutyrate, and acetone—are synthesized from acetyl CoA in liver mitochondria and secreted into the blood for use as a fuel by some tissues such as heart muscle.

D-3-Hydroxybutyrate is formed upon the

•reduction of acetoacetate. Acetone is generated by the spontaneous decarboxylation of acetoacetate.

In tissues using ketone bodies, D-3-hydroxybutyrate is oxidized to

acetoacetate, which is ultimately metabolized to two molecules of acetyl CoA.

Formation of Ketone Bodies

. The ketone bodies—acetoacetate, d-3-hydroxybutyrate, and acetone—are formed from acetyl CoA primarily in the liver. Enzymes catalyzing these reactions are (1) 3-ketothiolase, (2) hydroxymethylglutaryl CoA synthase, (3) hydroxymethylglutaryl CoA cleavage enzyme, and (4) d-3-hydroxybutyrate dehydrogenase. Acetoacetate spontaneously decarboxylates to form acetone.

Utilization of D-3-Hydroxybutyrate and Acetoacetate as a Fuel

d-3-Hydroxybutyrate is oxidized to acetoacetate with the formation of NADH. Acetoacetate is then converted into two molecules of acetyl CoA, which then enter the citric acid cycle.

Fats are converted into

acetyl CoA, which is then processed by the citric acid cycle

Oxaloacetate, a citric acid cycle intermediate, is a precursor to

Oxaloacetate, a citric acid cycle intermediate, is a precursor to

acetyl CoA derived from fats cannot lead to the net synthesis of oxaloacetate or glucose because

although two carbons enter the cycle when acetyl CoA condenses with oxaloacetate, two carbons are lost as CO2 before oxaloacetate is regenerated.

Why might D-3-hydroxybutyrate be considered a superior ketone body compared with acetoacetate?

Ketone bodies are

moderately strong acids

excess production can lead to

acidosis

An overproduction of ketone bodies can occur when

•diabetes, a condition resulting from a lack of insulin function, is untreated. The resulting acidosis is called diabetic ketosis.

If insulin is absent or not functioning

glucose cannot enter cells. All energy must be derived from fats, leading to the production of acetyl CoA.

fatty acid release from adipose tissue is enhanced in the absence of

insulin function

How Diabetic Ketosis Results When Insulin is Absent

In the absence of insulin, fats are released from adipose tissue, and glucose cannot be absorbed by the liver or adipose tissue. The liver degrades the fatty acids by b oxidation but cannot process the acetyl CoA because of a lack of glucose-derived oxaloacetate (OAA). Excess ketone bodies are formed and released into the blood. Abbreviation: CAC, citric acid cycle.

Glucose is the

predominant fuel for the br

During starvation, protein degradation is initially the source of

carbons for gluconeogenesis in the liver. The glucose is then released into the blood for the brain to use.

After several days of fasting

the brain begins to use ketone bodies as a fuel

Ketone body use curtails protein degradation and thus prevents

•tissue failure. Moreover, ketone bodies are synthesized from fats, the largest energy store in the body.

After depletion of triacylglycerols.. what happens

protein degradation accelerates, and death inevitably results from a loss of heart, liver, or kidney function. A person’s survival time is mainly determined by the size of the triacylglycerol depot.

Fuel Reserves in a Typical 70-kg (154-lb) Man

Most glycogen is in the muscle

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Most TAG is in adipose

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Most proteins in the body reside in muscles

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Brain stores almost nothing

Fuel choice during starvation

The plasma levels of fatty acids and ketone bodies increase in starvation, whereas that of glucose decreases.

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A week out, ketone bodies are being used for the majority of energy needs in the body.

Saturated and trans unsaturated fatty acids are synthesized commercially to enhance

the shelf life and heat stability of fats for food preparation

Studies suggest that excess consumption of these fats promote

obesity, atherosclerosis, and type 2 diabetes

The first stage of fatty acid synthesis is

transfer of acetyl CoA out of the mitochondria into the cytoplasm. Citrate is transported into the cytoplasm and cleaved into oxaloacetate and acetyl CoA

The second stage of Fatty Acid Synthesis is

1.the activation of acetyl CoA to form malonyl CoA.

The third stage of fatty acid synthesis is

the repetitive addition and reduction of two carbon units to synthesize C16 fatty acid. Synthesis occurs on an acyl carrier protein, a molecular scaffold

Citrate, synthesized in the mitochondria, is transported to the

cytoplasm and cleaved by ATP-citrate lyase to generate acetyl CoA for fatty acid synthesis

Fatty acid synthesis requires

reducing power in the form of NADPH

Some NADPH can be formed from the

oxidation of oxaloacetate, generated by ATP-citrate lyase, by the combined action of cytoplasmic malate dehydrogenase and malic enzyme.

Malate dehydrogenase reaction

Malic enzyme reaction

Pyruvate formed by malic enzyme enters the mitochondria where it is converted into

oxaloacetate by pyruvate carboxylase.

The sum of the reactions catalyzed by malate dehydrogenase, malic enzyme, and pyruvate carboxylase is:

The sum of the reactions catalyzed by malate dehydrogenase, malic enzyme, and pyruvate carboxylase is

Additional NADPH is synthesized by

the pentose phosphate pathway

Malonyl CoA is synthesized from acetyl CoA by

acetyl CoA carboxylase 1, a biotin-requiring enzyme

The formation of malonyl CoA occurs in two steps

Fatty acid synthase, a complex of enzymes, catalyzes

the formation of fatty acids.

Fatty acid synthesis occurs on

the acyl carrier protein (ACP), a polypeptide with structure similar to CoA. Intermediates are linked to the sulfhydryl group of the phosphopantetheine group attached to ACP.