Chapter 28: Fatty Acid Synthesis Flashcards by Jennifer Lyons

Most of our need for fats and lipids are met by our…

Diet

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Fatty acid synthesis occurs in the…

Cytosol

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When glucose is abundant, a large amount of _____ is produced that can be used for FA synthesis in cytosol.

Acetyl CoA

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The first of 3 stages of FA synthesis is:

The transfer of acetyl CoA out of the mitochondria into the cytoplasm

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The second of 3 stages of FA synthesis is:

The activation of acetyl CoA to form malonyl CoA

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The third of 3 stages of FA sythesis is:

The repetitive addition and reduction of two carbon units

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Citrate, synthesized in the _____, is transported to the _____ and cleaved by _____ to generate acetyl CoA for FA synthesis.

Synthesized in mitochondria and transported to the cytoplasm and cleaved by ATP-citrate lyase

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FA Synthesis requires reducing power in the form of…

NADPH

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Some NADPH is formed from the oxidation of _____ to _____.

Oxaloacetate to Pyruvate

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Additional NADPH comes from _____.

Pentose Phosphate Pathway

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The formation of _____ is the committed step in FA synthesis.

Malonyl CoA

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Malonyl CoA is synthesized by _____, a biotin-requiring enzyme.

Acetyl CoA carboxylase

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What catalyzes the irreversible rate-limiting step of FA synthesis?

Acetyl CoA carboxylase

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What catalyzes the formation of fatty acids?

Fatty acid synthase

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FA synthesis occurs on the _____, a polypeptide link to CoA.

Acyl carrier protein (ACP)

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What attaches substrates to the ACP?

Transacylases

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FA Synthesis consists of a series of reactions. What are they?

Condensation, reduction, dehydration and reduction

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What catalyzes the condensation of acetyl ACP and malonyl ACP to form acetoacetyl ACP?

B-ketoacyl synthase

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The next 3 steps convert the keto group at carbon 3 to a methylene group, forming _____.

Butyryl ACP

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_____ are consumed as reducing power.

2 NADPH

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Acetyl ACP to Malonyl ACP (required) convert to what via a condensation reaction?

Acetoacetyl ACP

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Acetoacetyl ACP converts to _____ via a reduction reaction.

D-3-hydroxbutyryl ACP

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D-3-Hydroxbutyryl ACP converts to _____ via a dehydration reaction.

Crotonyl ACP

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Crotonyl ACP converts to _____ via a reduction reaction.

Butyryl ACP

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Elongation of FA Chain proceeds by addition of 2 carbons from \_\_\_\_\_.

Malonyl ACP

The second round of synthesis begins with the condensation of _____ with the newly synthesized \_\_\_\_\_, forming \_\_\_\_\_.

Condensation of malonyl CoA with butyryl ACP, forming C6-beta-ketoacyl ACP

The reduction, dehydration, reduction sequence is \_\_\_\_\_.

Repeated

Synthesis continues until \_\_\_\_\_, which is cleaved by thioesterase to yield \_\_\_\_\_.

**C16-acyl ACP** to yield **palmitate**

The synthesis of palmitate requires?

* 8 Acetyl CoA * 14 NADPH * 7 ATP

Mammalian FA synthase is composed of one large single polypeptide chain that consists of 2 compartments:

1. Selecting and condensing compartment - condenses the acetyl and malonyl substrates 2. Modification compartment - carries out the reduction and dehydration activities required for elongation

Tumors require large amounts of _____ to produce precursors for membrane synthesis.

Fatty acid synthase

Fatty acid synthase inhibitors...

Slow tumor growth

Mice treated with fatty acid synthase inhibitors also showed dramatic _____ and may be used to treat \_\_\_\_\_.

Weight loss; obesity

Fatty acid synthase cannot generate fatty acids longer than \_\_\_\_\_.

C16 Palmitate

In order to have longer fatty acids, they must be synthesized by \_\_\_\_\_.

Enzymes attached to the endoplasmic reticulum

The enzymes that elongate fatty acids extend palmitate by \_\_\_\_\_, using _____ as a substrate.

Adding two carbon units, using malonyl CoA

Membrane-bound enzymes generate \_\_\_\_\_.

Unsaturated fatty acids

\_\_\_\_\_ cannot introduce **double bonds** during FA synthesis.

Eukaryotes

What introduce double bonds into saturated FAs?

Enzymes bound to the endoplasmic reticulum

Mammals lack the enzymes that introduce double bonds beyond \_\_\_\_\_.

Carbon 9

What are the two essential fatty acids that must be obtained from the diet?

Linoleate (C18:2) and Linolenate (C18:3)

What is a key regulator of Fatty Acid Metabolism?

Acetyl CoA Carboxylase

There are 3 mechanisms of regulation of fatty acid metabolism. With Acetyl CoA Carboxylase being the key regulator, what is it inhibited by?

* AMPK * Glucagon * Epinephrine * Palmitoyl CoA

There are 3 mechanisms of regulation of fatty acid metabolism. With Acetyl CoA Carboxylase being the key regulator, what is it stimulated by?

* Protein phosphatase 2A (PP2A) * Citrate * Insulin

**How** does Glucagon and Epinephrine affect Acetyl CoA Carboxylase? Insulin?

**Glucagon** and **epinephrine** inhibit carboxylase by _enhancing AMPK activity._ **Insulin** activates the carboxylase by causing its _dephosphorylation._

Excess ethanol consumption can cause \_\_\_\_\_.

Liver damage

Ethanol cannot be excreted, it must be...

Metabolized in the liver

One pathway for ethanol processing consists of two steps and leads to \_\_\_\_\_.

Excess production of NADH

Excess NADH inhibits \_\_\_\_\_. This results in \_\_\_\_\_.

* Inhibits gluconeogenesis * Results in: Hypoglycemia

Excess NADH inhibits _____ and stimulates \_\_\_\_\_, leading to accumulation of fats in liver, known as \_\_\_\_\_.

* Inhibits fatty acid degradation * Stimulates fatty acid synthesis * Results in: fatty liver

Fatty Acid Synthesis committed step:

Acetyl CoA carboxylase

Fatty Acid Degradation committed step:

Carnitine acyltransferase I

FA Degradation inhibited by \_\_\_\_\_.

Malonyl CoA

Liver converts some of the acetate to acetyl CoA, which cannot be processed by _____ due to inhibition by \_\_\_\_\_.

Citric acid cycle due to inhibition of NADH

The build-up of acetyl CoA can lead to _____ by the liver, which exacerbates the \_\_\_\_\_.

Ketone body secretion which exacerbates the lactic acidosis

If acetate cannot be processed, _____ accumulates.

Acetaldehyde

Acetaldehyde is very reactive and modifies reactive groups of proteins, causing \_\_\_\_\_.

A loss of protein function

As protein damage accumulates,

Liver function can fail

3 Stages of liver damage by excess ethanol consumption:

1. Fatty liver (Liver can be 2X the normal size) 2. Alcoholic hepatitis 3. Cirrhosis (More shrunken liver)

Chronic ethanol ingestion alters carbohydrate metabolism and leads to a fatty liver due primarily to an increase in which of the following? * NADH * NADPH * ATP * ADP * None of the above

NADH

Phospholipid synthesis does NOT require:

Sphinogsine

Tay-Sachs disease is caused by an inability to degrade:

Gangliosides

Fatty acid synthesis occurs in...

Occurs in the cytosol in all species

. The rate limiting step for fatty acid synthesis is promoted by:

Acetyl CoA carboxylase

During the chain elongation step of fatty acid synthesis, the newly added carbons come directly from:

Malonyl ACP

T or F: Acetyl CoA carboxylase is found exclusively in the mitochondria.

False

High concentrations of acetyl CoA in the mitochondria:

Lead to increased transport of citrate from the mitochondria to the cytosol

T or F: High levels of insulin stimulate acetyl CoA carboxylase.

True

T or F: Acetyl CoA carboxylase produces malonyl CoA.

True

T or F: Acetyl CoA carboxylase catalyzes the rate-limiting step for fatty acid synthesis.

True

T or F: Acetyl CoA carboxylase is regulated by phosphorylation and allosteric modification.

True

Fatty acids are elongated and desaturated by...

Enzymes attached to the ER

Excess NADH enhances \_\_\_\_\_. This results in \_\_\_\_\_.

* Enhances lactate production * Results in: Lactic Acidosis

Fatty acid oxidation is increased by: * Low insulin levels * Low carbohydrate levels * High epinephrine levels * High glucagon levels

All are correct

Fatty acid oxidation...

Requires activation of fatty acids to the CoA form

What is the purpose of the carnitine shuttle system?

To transport fatty acids from the cytosol to the mitochondrial matrix

T or F about fatty acids in mammals: Double bonds are added during the synthesis of fatty acids

False

T or F: About fatty acids in mammals: Fatty acids in triacylglycerols provide only limited energy storage

False

T or F: about fatty acids in mammals: Elongases must be used to synthesize fatty acids longer than 18 carbons

True

T or F: about fatty acids in mammals: Mammals can synthesize all the fatty acids they need

False

T or F about fatty acids in mammals: Fatty acids are rarely made in mammals

False

Which statement comparing fatty acid synthesis to fatty acid degradation is TRUE about both processes? * They both occur in the cytosol * They both utilize intermediates covalently attached to ACP * They both can be regulated by insulin levels * They both require reduction steps * They both generate energy

They both can be regulated by insulin levels

The building block for triacylglycerol synthesis is:

Glycerol 3-phosphate