Fatty Acid Metabolism Flashcards by Joel Glotfelty

A heterogeneous group of water-insoluble (hydrophobic) organic molecules that can be extracted from tissues by nonpolar solvents

Lipids

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Serve not only as a major source of energy for the body, but they also provide the means for separating cells and subcellular structures into distinct compartments

Lipids

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The digestion of triacylglycerol is initiated in the stomach by an acid-stable lipase called

Lingual Lipase

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Also produced that can hydrolyze triacylglycerol molecules containing fatty acids of short or medium chain length

Gastric Lipase

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More useful in the neonate, with a less acidified stomach and a diet of breast milk abundant in medium and short chain length TAGs

Gastric Lipase

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Activates a pancreatic, phosphatidylinositol triphosphate pathway

CCK

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Dietary triacylglycerol is degraded by pancreatic lipase which preferentially removes the fatty acids at carbons #1 and #3, leaving a

2-monoacylglycerol

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Binds to both the water-lipid interface and to pancreatic lipase, thereby anchoring and activating the enzyme

-a small pancreatic enzyme

Colipase

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This enzyme acts on cholesterol esters, monoacylglycerol, or other lipid esters such as esters of vitamin A

-found in pancreatic juice

Esterase

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Phospholipids are degraded by a two-step process. Pancreatic juice is rich in the proenzyme

Phospholipase A2

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This enzyme removes the fatty acid at carbon #2 of the phopholipid, leaving a lysophospholipid

Phospholipase A2

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The remaining fatty acid at carbon #1 is removed by lysophospholipase, leaving a

Glycerylphosphorycholine

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Free fatty acids, free cholesterol, and 2-

monoacylglycerol are the major products of dietary lipid degradation in the

Jejunum

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The double bonds in human fatty acids are almost always of the

Cis configuration

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Glucose that is not utilized in glycolysis, glycogen synthesis, the HMP pathway, are readily converted to

Fatty acids (stored as TAGs)

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Occurs in the cytoplasm of cells of liver, adipose, intestine, lactating mammary glands and to a lesser extent, kidney

Fatty acid synthesis

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The process of FA synthesis incorporates carbons from acetyl CoA into the growing fatty acid chain, utilizing

ATP and NADPH as cofactors

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Prior to the first catalytic step in fatty acid synthesis, we need to see the transfer of

Acetate units from mitochondrial acetyl CoA to cytoplasm

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This transfer is performed via a

Citrate intermediate

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This process of translocation across the inner mitochondrial membrane occurs when the matrix-side citrate concentration is

High

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The first enzyme of the faty acid synthesis pathyway is

-the site of regulation

Acetyl CoA carboxylase

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The remaining several reactions in fatty acid synthesis are catalyzed by a multienzyme complex called

Fatty acid synthase (FAS)

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In humans, this enzyme complex consists of a dimer, each monomer of which has

7 enzymatic domains

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The FAS also has a domain that covalently binds a molecule of

Phospantetheine

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In prokaryotes the phosphopantetheine- | containing domain is a separate peptide, and is referred to as the

Acyl Carrier Protein (ACP)

The product of fatty acid synthase is the 16-carbon saturated fatty acid

Palmitic Acid

Fatty acids can be elongated in the

Mitochondria or ER

Chain desaturation occurs in the

Requires biotin as a cofactor

Acetyl CoA Carboxylase (also PK and propionyl carboxylase)

What is the committed step of FA synthesis?

Acetyl CoA Carboxylase

Short-term control by allosteric modifiers includes

Citrate

Allosterically activates the enzyme by promoting formation of large polymers

Citrate

Inhibit acetyl CoA carboxylase by breaking down those polymers

Palmitoyl CoA (and malonyl CoA)

Inhibits acetyl CoA carboxylase through cAMP-mediated phosphorylation

Glucagon

Stimultes acetyl CoA carboxylase by dephosphorylation

Insulin

Long-term control of FA synthesis is exerted via diet, by way of

Insulin and Glucagon

Both a high-carbohydrate diet or a fat-free diet stimulate fatty acid synthesis through increased synthesis of

Acetyl CoA Carboxylase

In contrast, a high-fat diet or fasting (causing increased glucagon levels) results in

Inhibition of FA synthesis

Glucose also contributes to the synthesis of fatty acids and, therefore, to TAG production, by the diversion of

Pyruvate derived acetyl CoA to the enzymes of FA synthesis

Synthesis of glycerol phosphate occurs in both the

Adipose and the liver

Activates fatty acids to their ‘CoA’ form

FA synthetase (thiokinase)

Attaches the fatty acid moieties to the glycerol phosphate “backbone” in a process that also requires a phosphotase

Acyltransferase

Removes the phosphate prior to the addition of the third fatty acid

The Phosphotase

Stored in the cytosol as “depot” fat

Adipose derived TAG

On the other hand, liver- | derived triacylglycerol is packaged in the lipoprotein

VLDL

Fatty acids stored in adipose tissue in the form of neutral triacylglycerol serve as a major

Fuel storage depot

Depot fat mobilization is characterized by the release of free fatty acids from their triacylglycerol parent. The release is initiated by the enzyme

Hormone sensitive lipase

Removes a fatty acid from either C1 or C3 of the triacylglycerol

Hormone sensitive lipase

Next, additional lipases specific for mono- or diacylglycerol degradation remove the remaining

Fatty acids

Following their release, they exit the adipose cell and are transported in the circulation bound to

Albumin

The glycerol molecule may be taken up by liver for

Gluconeogenesis or FA synthesis

The major pathway for catabolism of saturated fatty acids is called

B-oxidation

Two-carbon units are successively removed from the carboxyl end of the fatty acid, in the form of acetyl-CoA

B-oxidation

Subsequently can enter the TCA cycle for additional oxidation and energy generation via the electron transport chain and ATP synthase

Acetyl CoA

The first step of B-oxidation is the conversion of the fatty acid to its activated form called

Fatty Acyl CoA

Because b-oxidation occurs in the mitochondria, the fatty acid must be transported across the mitochondrial membrane. This requires the carrier

Carnitine

Consists of two enzymes, carnitine acyl transferase (CAT) I and II

Carnitine Shuttle

Step one of B-oxidation is the transport of fatty acyl CoA across the outer mitochondrial membrane by

CAT I

Step 2 of B-oxidation takes place on the inner mitochondrial membrane and is catalyzed by

CAT-II

Congenital absence of a member of the carnitine system in skeletal muscle results in diminished ability to use

Long-chain FA's as fuel

This often takes the form of

Exercise intolerance

Inhibits carnitine palmitoyltransferase I, thus preventing the entry of acyl groups into the mitochondria

Malonyl CoA

Transferred from the Matrix into the intermembrane space to be resused

Carnitine

The steps in B-oxidation are a recurring sequence of four reactions that result in the shortening of the carbon chain by

2 carbons per sequence

These four steps are repeated for fatty acids of even-numbered carbon chains (n/2 - 1) times, each cycle producing

1 acetyl CoA, 1 ADH, and 1 FADH2

The final cleavage in B-oxidation releases

2 acetyl CoAs

The three activities present in the mitochondrial “tri functional protein.” are the

Hydratase, dehydrogenase, and acyltransferase (thiolase)

The B-oxidation of a saturated fatty acid with an uneven number of carbon atoms proceeds by the same reaction steps as that of fatty acids with an even number of carbons until the

Final 3 carbons (propionyl CoA) are reached

The processing of propionyl CoA requires which three things?

Biotin, Vitamin B12, and the enzyme medium-chain acyl-CoA dehydrogenase

The processing of propionyl CoA results in -can be used in the TCA cycle

Succinyl-CoA

The liver has the enzymatic capacity to divert acetyl CoA derived from fatty acid or pyruvate oxidation into

Ketone Body Synthesis

Exit the liver and are transported via the blood to peripheral tissues where they can be reconverted to acetyl CoA and then oxidized via the TCA cycle

Ketone Bodies

Can the liver utilize ketone bodies for energy?

Can occur by: 1. ) The incomplete breakdown of fatty acids, or... 2. ) The reversal of the thiolase reaction of fatty acid oxidation.

The first step of ketone body synthesis

Next, a third molecule of acetyl CoA condenses with acetoacetyl CoA to produce

HMG CoA

The formation of HMG CoA is catalyzed by

HMG CoA synthase

Finally, HMG CoA is cleaved by

HMG CoA Lyase

This cleavage releases

Acetyl CoA and acetoacetate

Can be reduced to form 3-hydroxybutyrate or can spontaneously decarboxylate to produce acetone

Acetoacetate

In peripheral tissues, 3- | hydroxybutyrate is reoxidized to acetoacetate, which is then converted to

Acetoacetyl CoA

Provided by succinyl CoA via 3-ketoacyl-CoA transferase

The Coenzyme A for this reaction

Missing in the liver, thus preventing it from metabolizing ketones for energy

3-ketoacetyl-CoA Transferase

Then, the acetoacetyl CoA is rapidly removed by

Thiolase

Soluble derivatives of fatty acids that can be used by peripheral organs to preserve glucose supplies for glucose-demaning organs

Ketone bodies

Can metabolize ketone bodies in the later stages of a fast

The brain

There’s a sharp edge to this, however, in that as ketone body levels increase, there is also increased strain on the system that regulates

Blood pH

The term applied to this advanced state of starvation, and may be detected by the odor of acetone on the breath

Ketoacidosis

Fatty Acid Metabolism Flashcards

(87 cards)