ch21

Phospholipases

hydrolyze phospholipids

isoprene units

Involvement of _______ is key to the biosynthesis of steroids

Phosphorylation of the primary alcohol of mevalonate followed by phosphorylation of the 3° alcohol

Isopentenyl pyrophosphate is produced after:

fatty acids; hydrolyzed

Triacylglycerols and phosphoacylglycerols Have ____ as part of their covalently bonded structures and the bond b/w the fatty acid & the rest if the molecule can be ___.

Mn2+, biotin, ATP

acetyl-CoA carboxylase complex requires:

acetyl-CoA carboxylase complex

carboxylation of acetyl-CoA is catalyzed by

malonyl-CoA

carboxylation of acetyl-CoA key intermediate:

found on the cytosol side of the inner mitochondrial membrane with a specificity for acyl groups between 14 and 18 carbons long; transfers a fatty acyl group to carnitine in fatty acid activation

carnitine palmitoyltransferase (aka CPT-I/Carnitine acyltransferase) What does it do? Where is it found?

Phosphoacylglycerol

-Key component of biological membranes -May have multiple sites of action

Triacylglycerol

-Main storage form of the chemical energy for most organisms -Carbon chains are in a highly reduced form

Bile salts are made from cholesterol, and cholesterol is taken from the body into the intestine in the bile fluid.

A drug that reduces blood cholesterol has the effect of stimulating the production of bile salts. How might this result in lower blood cholesterol?

The metallic taste may be due to acetone, which means that your friend may have a mild state of ketosis. perhaps recommend either backing off from such a low-calorie diet or drinking more water to flush the system more thoroughly.

A friend who is trying to lose weight complains about the odd taste in his mouth in the mornings. He says it seems like a filling has broken loose, and the metallic sensation is bothersome. What would you say?

outer mitochondrial membrane; inner mitochondrial membrane

Acyl-CoA can cross the ______ but not the ______.

ATP

Acyl-CoA synthetase catalyzes formation of the ester bond and requires ___ for its action

two-carbon acetyl group of acetyl-CoA

All carbon atoms of cholesterol and steroids synthesized from cholesterol are derived from the:

palmitoyl-CoA and serine

Biosynthesis of sphingolipids requires

Two acetyl-CoA molecules combine to form acetoacetyl-CoA. This can then release coenzyme A to yield acetoacetate, which can be converted either to beta-hydroxybutyrate or to acetone.

Briefly outline the reactions involved in ketone production.

condensation of two molecules of acetyl-CoA

Cholesterol biosynthesis begins with the:

packaged

Cholesterol must be _____for transport in the bloodstream

thiolase

Cleavage of the alpha-ketoacyl-CoA catalyzed by

The two pathways have in common the involvement of acetyl-CoA and thioesters, and each round of breakdown or synthesis involves two-carbon units. The differences: malonyl-CoA is involved in biosynthesis, not in breakdown; thioesters involve CoA in breakdown and involve acyl carrier proteins in biosynthesis; biosynthesis occurs in the cytosol, but breakdown occurs in the mitochondrial matrix; breakdown is an oxidative process that requires and FAD and produces ATP by electron transport and oxidative phosphorylation, whereas biosynthesis is a reductive process that requires NADPH and ATP.

Compare and contrast the pathways of fatty acid breakdown and biosynthesis. What features do these two pathways have in common? How do they differ?

For an odd-chain fatty acid, beta-oxidation proceeds normally until the last round. When five carbons are left, that round of beta-oxidation releases one acetyl-CoA and one propionyl-CoA. Propionyl-CoA cannot be further metabolized by -oxidation; however, a separate set of enzymes converts propionyl-CoA into succinyl-CoA, which can then enter the citric acid cycle.

Describe briefly how beta-oxidation of an odd-chain fatty acid is different from that for an even-chain fatty acid.

Low-density lipoproteins (LDLs)

Transports cholesterol from liver to the rest of the body

1 mole of stearic acid to 9 moles of acetyl-CoA

Eight cycles of beta-oxidation are required for the oxidation of:

ATP

Energy released by the oxidation of acetyl-CoA formed by beta-oxidation of fatty acids can be used to produce __

greater

Energy yield per gram of fatty acid oxidized is _____ than that per gram of carbohydrate oxidized

cytosol; mitochondrial matrix

Esterification takes place in _______, but the rest of the reactions of fatty acid oxidation occur in the _____.

electron transport chain

FADH2 and NADH produced by b-oxidation and the citric acid cycle enter the:

activation of the molecule

Fatty acid oxidation begins with:

Isoprene units

Five-carbon groups that are used in biosynthesis of steroids

Pregnenolone

Formed from cholesterol and produces progesterone

In the liver, glycogen breakdown and gluconeogenesis would occur. In the muscle, glycogen breakdown and glycolysis would occur.

Given the nature of the hormonal activation of lipases, what carbohydrate pathways would be activated or inhibited under the same conditions?

brain, stomach, intestines, pancreas, adipose tissue

Hormones from _______________ stimulate and repress appetite

transesterification

In fatty acid activation, acyl group is transferred to carnitine, carried across the inner mitochondrial membrane, and transferred to mitochondrial CoA-SH by _______ reactions

A hormone signal activates adenylate cyclase, which makes cAMP. This activates protein kinases, which phosphorylate the lipases, thereby activating them.

How are lipases activated hormonally?

by beta-oxidation of fatty acids or by decarboxylation of pyruvate

How is Acetyl-CoA formed?

enoyl-CoA hydratase

Hydration of unsaturated acyl-CoA to produce a beta-hydroxyacyl-CoA catalyzed by

Lipases

Hydrolyze lipids

dimethylallyl pyrophosphate

In cholesterol biosynthesis enzyme-catalyzed isomerization of the carbon-carbon double bond gives :

reduction of the thioester that gives a primary alcohol

In cholesterol biosynthesis, formation of mevalonate is completed by:

acetoacetyl-CoA to produce β-hydroxy-β-methylglutaryl-CoA (HMG-CoA)

In cholesterol biosynthesis, the third molecule of acetyl-CoA condenses with:

squalene (C30)

In cholesterol biosynthesis, two molecules of farnesyl pyrophosphate (C15) condense to form

H+ loss to give farnesyl pyrophosphate

In cholesterol biosynthesis, what happens after Dimethylallyl pyrophosphate is converted to isopentenyl pyrophosphate?

isopentenyl pyrophosphate

In cholesterol biosynthesis, what is Dimethylallyl pyrophosphate is converted to

Fats cannot produce a net yield of glucose because they must enter the citric acid cycle as the two-carbon unit acetyl-CoA. However, an odd-chain fatty acid can be considered partially glucogenic because the final three carbons become succinyl-CoA and enter the citric acid cycle after the decarboxylation steps.

It has been stated many times that fatty acids cannot yield a net gain in carbohydrates. Why can odd-chain fatty acids be thought to break this rule to a small extent?

propionyl-CoA

Last beta oxidation cycle of odd-carbon fatty acids gives:

fatty acids and metabolites of fatty acids

Lipids, such as triacylglycerols, phosphoacylglycerols, and steroids, are derived from:

Carnitine

Molecule used in fatty acid metabolism to shuttle acyl groups across the inner mitochondrial membrane

melanocortins

Neurons that tend to inhibit eating produce _____.

citric acid cycle

Nine moles of acetyl-CoA produced from each mole of stearic acid enter the _____.

Acyl groups are esterified to carnitine to cross the inner mitochondrial membrane. There are transesterification reactions from the acyl-CoA to carnitine and from acylcarnitine to CoA

Outline the role of carnitine in the transport of acyl-CoA molecules into the mitochondrion. How many enzymes are involved? What are they called?

Step 1: biotin is carboxylated using bicarbonate ion as the source of the carboxyl group. Step 2: the carboxylated biotin is brought into proximity with enzyme-bound acetyl-CoA by a biotin carrier protein. Step 3: the carboxyl group is transferred to acetyl-CoA, forming malonyl-CoA.

Outline the steps involved in the production of malonyl-CoA from acetyl-CoA.

FAD-dependent acyl-CoA dehydrogenase

Oxidation of acyl-CoA to alpha, beta unsaturated acyl-CoA catalyzed by

carnitine palmitoyltransferase (aka CPT-I/Carnitine acyltransferase) & Carnitine palmitoyltransferase (CPT-II)

Transesterification reactions are catalyzed by

phosphatidates

Phosphoacylglycerols are based on _____, with the phosphate group esterified to another alcohol

HDL ("good cholesterol")

Regular strenuous exercise increases ___ levels and decreases the probability of heart disease

Beta Oxidation

Repeated series of reactions that cleaves two-carbon units from the carboxyl end of a fatty acid

Lipids

Represent an efficient way of storing chemical energy

HDL ("good cholesterol")

Smoking reduces the level of __ and is highly correlated with heart disease

acetyl-CoA by beta-oxidation

Starvation causes an organism to break down fats for energy, leading to the production of large amount of acetyl-CoA by beta-oxidation

Cholesterol

Steroid that occurs in cell membranes and is the precursor of other steroids

sphingosine, a long-chain amine

Structural basis of sphingolipids is:

false

T/F: Fatty Acid Biosynthesis anabolism the exact reversal of the reactions of beta oxidation?

false

T/F: it is possible to convert fatty acids to other lipids without acyl-CoA intermediates

High-density lipoproteins (HDLs)

Transports cholesterol back to the liver for degradation to bile acids

glycerol-3-phosphate

The glycerol portion of lipids is derived from:

acetyl-CoA produced is excessive when compared to the amount of oxaloacetate available to react with it (i.e when there is an imbalance in lipid catabolism, compared with carbohydrate catabolism. If fatty acids are being beta-oxidized to produce acetyl-CoA, but there is insufficient oxaloacetate because it is being drawn off for gluconeogenesis, the acetyl-CoA molecules combine to form ketone bodies.)

Under what conditions are ketone bodies produced?

Oxidation of acyl-CoA to alpha, beta unsaturated acyl-CoA Hydration of unsaturated acyl-CoA to produce a beta-hydroxyacyl-CoA Oxidation reaction, catalyzed by alpha-hydroxyacyl-CoA dehydrogenase, an NAD+ dependent enzyme Cleavage of the alpha-ketoacyl-CoA

What are the 4 rxns required for Beta Oxidation?

in prokaryotes, CTP reacts with phosphatidic acid to give a CDP-diacylglycerol. This reacts with serine to give phosphatidylserine, which decarboxylates to phosphatidylethanolamine. In eukaryotes, CDP-ethanolamine reacts with a diacylglycerol to give phosphatidylethanolamine.

What are the differences between synthesis of phosphatidylethanolamine in prokaryotes and eukaryotes?

Ghrelin is a peptide hormone that serves as a hunger signal. Cholecystokinin has the opposite effect.

What is ghrelin? What is its effect on appetite? Is there any substance that has an opposite effect?

Phospholipase A1 hydrolyzes the ester bond to carbon-1 of the glycerol backbone; phospholipase A2 hydrolyzes the ester bond to carbon-2 of the backbone

What is the difference between phospholipase A1 and A2 ?

Acyl-CoA dehydrogenase removes hydrogens from adjacent carbons, creating a double bond and using FAD as coenzyme. Beta-Hydroxy-CoA dehydrogenase oxidizes an alcohol group to a ketone group and uses as a coenzyme.

What is the difference between the type of oxidation catalyzed by acyl-CoA dehydrogenase and that catalyzed by beta-hydroxy-CoA dehydrogenase?

oxidation of unsaturated fatty acids does not generate as many ATP

What is the difference in products of oxidation of unsaturated fatty acids when compared to oxidation of saturated fatty acids with the same number of carbons?

It is a molecule that commits itself to fatty acid synthesis. It is also a potent inhibitor of carnitine acyltransferase I, thereby shutting down beta-oxidation.

What is the metabolic importance of malonyl-CoA?

Acyl-CoAs are high-energy compounds. An acyl-CoA has sufficient energy to initiate the beta-oxidation process. The CoA is also a tag indicating that the molecule is destined for oxidation.

What is the metabolic purpose of linking a fatty acid to coenzyme A?

Acetyl groups condense with oxaloacetate to form citrate, which can cross the mitochondrial membrane. Acetyl groups are regenerated in the cytosol by the reverse reaction.

What is the role of citrate in the transport of acetyl groups from the mitochondrion to the cytosol?

Melanocortins stimulate a chain of events that suppress appetite.

What is the role of melanocortins in control of appetite?

The glycerol comes from degradation of other acylglycerols or from glycerol-3-phosphate derived from glycolysis.

What is the source of the glycerol in triacylglycerol synthesis?

short term regulation

What kind effects do Ghrelin and cholecystokinin have on eating/appetite?

long term regulation

What kind effects do Insulin and leptin have on eating/appetite?

Neuropeptide Y operates in the central nervous system. Its function is to start a chain of events that stimulates appetite.

What role does neuropeptide Y play in control of appetite? Where do its effects take place?

cytosol

Where do Fatty Acid Biosynthesis anabolic reactions occur?

The processing of the acetyl-CoA through the citric acid cycle and the electron transport chain produces more energy than the processing of the NADH and produced during beta-oxidation.

Which generates more ATP—the processing of the reduced electron equivalents formed during beta-oxidation through the electron transport chain, or the processing of the acetyl-CoA generated from beta-oxidation through the citric acid cycle and the electron transport chain?

Bile acids and steroid hormones.

Which molecules have cholesterol as a precursor?

weight is not a critical factor, and it takes more energy to make fat or oil than it does to make starch. In the case of plant seeds, "compact" energy is beneficial, because the seed must be self-sufficient until enough growth has occurred to permit photosynthesis

Why don't plants use fats/oils as their major energy storage compound?

If the reason for passing out is uncontrolled diabetes, the doctor expects to smell acetone on the breath, since the otherwise unused sugars are being converted to fats and ketone bodies.

Why might a doctor smell the breath of a person known to have diabetes who has just passed out?

Ethanol is converted to acetaldehyde and then to acetic acid. Humans can use that acetic acid only for energy, or they can convert it to fatty acids and other lipids.

Why might a person who is an alcoholic have a "fatty liver"?

Cholesterol is nonpolar and cannot dissolve in blood, which is an aqueous medium.

Why must cholesterol be packaged for transport rather than occurring freely in the bloodstream?

The oxidation of unsaturated fatty acids to acetyl-CoA requires a cis-trans isomerization and an epimerization, reactions that are not found in the oxidation of saturated fatty acids.

You hear a fellow student say that the oxidation of unsaturated fatty acids requires exactly the same group of enzymes as the oxidation of saturated fatty acids. Is the statement true or false? Why?

NPY/AgRP-producing neurons

____ stimulate eating and produce neuropeptide Y (NPY)

Progesterone

_____ is a precursor for testosterone and estradiol

Cis-trans isomerization

_____ is needed to convert monounsaturated fatty acids to acetyl-CoA

Metabolic oxidation of lipids

_____ releases large quantities of energy through production of acetyl-CoA, NADH, and FADH2

ketone bodies

______ are formed when the amount of acetyl-CoA produced is excessive when compared to the amount of oxaloacetate available to react with it

Thioester bond is formed between the carboxyl group of the fatty acids and the thiol group of CoA-SH

fatty acid activation in lipid metabolism

Acetone, beta-hydroxybutyrate, and acetoacetate

what are some examples of ketone bodies?

oxidation of fatty acids

what is the chief source of energy in the catabolism of lipids?

liver mitochondria

where are ketone bodies formed?

cytosol

where does fatty acid biosynthesis carboxylation of acetyl-CoA occur?

mitochondrial matrix

where is Carnitine palmitoyltransferase (CPT-II) found?