Week 13: Glycogen Synthesis, Pentose Phosphate Pathway, Fatty Acid and Lipid Metabolism Flashcards by Salina H Huy

Why is it essential that the regulatory mechanisms that activate glycogen synthesis also deactivate glycogen phosphorylase?

Because these two processes occur in the _______ in the cell, this regulation makes the ______ more efficient.

Such a regulatory mechanism prevents the simultaneous ______ of glucose monomers, preventing unnecessary reactions.

same location, net process

addition and removal

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The free energy of formation of UDP-glucose from UTP and glucose-1-phosphate is close to zero. The pyrophosphate that is produced in this reaction, when hydrolyzed to two phosphate ions, ______ considerable energy. The coupling of these two reactions makes the net reaction ______.

The addition of glucose to glycogen as UDP-glucose is converted to UDP is approximately energy-neutral. Thus, the overall formation of glycogen is exergonic. The net effect is that some of the energy stored in the terminal phosphodiester bond of UTP and some of the energy stored in the phosphoester bond of glucose-1-phosphate is stored in glucose-glucose bonds in glycogen and some is lost in the hydrolysis of pyrophosphate.

releases, exergonic

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Increasing the level of ATP favors both ____ and ______.

Decreasing the level of fructose-1,6-bisphosphate tends to stimulate ______ rather than _______.

The level of fructose-6-phosphate does not have a marked regulatory effect on _______.

gluconeogenesis and glycogen synthesis

glycolysis, gluconeogenesis or glycogen synthesis

gluconeogenesis or glycogen synthesis

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Why is a different reducing agent (NADPH) is used in anabolic reactions rather than NADH, which is used in catabolic reactions?

This separation helps to untangle the two pathways so that the reactions are ______.

independently controllable

Anabolic and catabolic reactions must be regulated independently. Having two different redox species for the two pathways makes it much easier to regulate each pathway’s reactions without interfering with the other pathway’s reactions.

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What are reasons that a fatty acid is linked to coenzyme A for metabolic purposes?

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

high-energy, energy

β-oxidation

molecular tag

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Calculate the ATP yield for the complete oxidation of the 20-carbon saturated fatty acid arachidic acid.

(You should consider the β-oxidation steps, processing of acetyl-CoA through the citric acid cycle, and electron transport. Production of one GTP should be considered the equivalent of production of one ATP. Enter your answer to three significant figures.)

___ ATPs are gained for each arachidic acid oxidized

134

The 20-carbon arachidic acid will go through 9 rounds of β-oxidation. This will produce 9 FADH2s, 9 NADHs, and 10 acetyl-CoAs. These 10 acetyl-CoAs will each produce one FADH2, one GTP, and three NADHs in the citric acid cycle for a total of 10 FADH2s, 30 NADHs, and 10 GTPs from this cycle. There are thus a total of 39 NADHs and 19 FADH2s produced per arachidic acid.

Oxidation of one FADH2 via electron transport produces 1.5 ATPs while oxidation of one NADH via electron transport produces 2.5 ATPs. Thus, oxidation of the NADH produced in the metabolism of arachidic acid is responsible for the synthesis of 2.5 × 39 = 97.5 ATPs and oxidation of FADH2 is responsible for 1.5 × 19 = 28.5 ATPs.

The net production of ATP plus GTP is thus 10 + 97.5 + 28.5 = 136 per arachidic acid. A two ATP-equivalent is consumed in the initial activation step, so the overall net ATP gain is 134 ATPs per arachidic acid that is fully oxidized.

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Calculate the ATP yield for the complete oxidation of a 21-carbon saturated fatty acid.

_____ ATPs are gained for each 21-carbon fatty acid oxidized

129

The 21-carbon fatty acid will go through 9 rounds of β-oxidation. This will produce 9 FADH2s, 9 NADHs, 9 acetyl-CoAs, and one proprionyl-CoA. The 9 acetyl-CoAs will each produce one FADH2, one GTP, and three NADHs in the citric acid cycle for a total of 9 FADH2s, 27 NADHs, and 9 GTPs from this cycle. The proprionyl-CoA will produce one NADH and one FADH2 via the citric acid cycle along with one GTP. There are thus a total of 37 NADHs and 19 FADH2s produced per 21-carbon fatty acid.

Oxidation of one FADH2 via electron transport produces 1.5 ATPs while oxidation of one NADH via electron transport produces 2.5 ATPs. Thus, oxidation of the NADH produced in the metabolism of the 21-carbon fatty acid is responsible for the synthesis of 2.5 × 37 = 92.5 ATPs and oxidation of FADH2 is responsible for 1.5 × 19 = 28.5 ATPs.

The net production of ATP plus GTP is thus 9 + 1 + 92.5 + 28.5 = 131 per fatty acid. A two ATP-equivalent is consumed in the initial activation step for the original fatty acid and one ATP-equivalent is used in the conversion of proprionyl-CoA to succinyl-CoA, so the overall net ATP gain is 128 ATPs per 21-carbon fatty acid that is fully oxidized.

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Calculate the ATP yield for the complete oxidation of the 20-carbon unsaturated fatty acid gadoleic acid (a 20:1-Δ9 fatty acid).

_____ ATPs are gained for each gadoleic acid oxidized

133

The 20-carbon gadoleic acid will go through 9 rounds of β-oxidation. This will produce 8 FADH2s, 9 NADHs, and 10 acetyl-CoAs. (If the fatty acid had been saturated, 9 FADH2s would have been produced in the β-oxidation cycles. One less is produced here because one of the oxidation steps catalyzed by acyl-CoA dehydrogenase is not needed due to the presence of the C=C double bond in the original fatty acid.)

The 10 acetyl-CoAs from above will each produce one FADH2, one GTP, and three NADHs in the citric acid cycle for a total of 10 FADH2s, 30 NADHs, and 10 GTPs from this cycle. There are thus a total of 39 NADHs and 18 FADH2s produced per gadoleic acid.

Oxidation of one FADH2 via electron transport produces 1.5 ATPs, while oxidation of one NADH via electron transport produces 2.5 ATPs. Thus, oxidation of the NADH produced in the metabolism of gadoleic acid is responsible for the synthesis of 2.5 × 39 = 97.5 ATPs and oxidation of FADH2 is responsible for 1.5 × 18 = 27.0 ATPs.

The net production of ATP plus GTP is thus 10 + 97.5 + 27.0 = 135 per gadoleic acid. A two ATP-equivalent is consumed in the initial activation step, so the overall net ATP gain is 133 ATPs per gadoleic acid that is fully oxidized.

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When oxaloacetate is in insufficient supply, as under starvation conditions, the ______ produced in β-oxidation cannot enter the ______ but rather is used to form ______.

acetyl-CoA

citric acid cycle

ketone bodies

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Ketone bodies are produced when ______ lags behind _______.

Ketone bodies are produced when ______ is in insufficient supply.

carbohydrate metabolism
lipid metabolism

oxaloacetate

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There are many differences in the pathways of fatty-acid breakdown and fatty-acid synthesis. Similarities include the use of ______ as a carrier, the use of ______ linkages, and a _____ unit that is fundamental to both pathways.

coenzyme A
thioester
two-carbon

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The source of the glycerol in triacylglycerol synthesis is from _______ derived from _______

glycerol-3-phosphate
glycolysis

Glycerol comes from the degradation of acylglycerols or from the glycerol-3-phosphate derived from the glycolysis pathway.

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_____ and _______ have cholesterol as a synthetic precursor.

Bile acids, steroid hormones (estradiol)

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

Cholesterol is _____ and will not readily _____ in the aqueous bloodstream.

______, which effective solubilize cholesterol, are needed to transport cholesterol in the blood.

nonpolar, dissolve

Carrier proteins

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The pentose phosphate pathway can make both NADPH and pentose phosphates in roughly equimolar amounts by using only ______ reactions.

The pentose phosphate pathway can make mostly NADPH by using the _____reactions, the _______ reactions, and ______.

The pentose phosphate pathway can make mostly pentose phosphates by using _____ and the ______ reactions in reverse.

oxidative

oxidative, transaldolase and transketolase, gluconeogenesis

glycolysis, transaldolase and transketolase

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UDP-glucose is used to ______ the glycogen chain
in synthesis.

extend

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______ is the key regulatory enzyme in glycogen synthesis
* transfers a glucose moiety from ______ to the C-4 terminal residue of a glycogen chain to form an _______.
* requires an oligosaccharide of glucose residues as a primer.

Glycogenin
a small protein homodimer that synthesizes the ______.
Each subunit of glycogenin generates an oligosaccharide of glucose residues ______ glucosyl units long.
_______ then extends this primer.

Glycogen synthase
UDP-glucose, α-1,4-glycosidic bond

primer, 10–20

Glycogen synthase

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Glycogen synthase adds to ______ ends, builds ______

non-reducing, straight chain

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Branching enzyme in branching reaction cleaves _______ linkages off chains that are at least _____ long and clips of ______.

a-1,4 linkages, 11 units, 7-8 units

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Glycogen synthase has:

Phosphorylated ____ form (usually _____) and unphosphorylated _____ form (more _____)
Note that phosphorylation has ______ effects on glycogen synthase than on glycogen phosphorylase
T (_____ active) and R (_____ active) forms

b, inactive
a, active
Unphosphorylated form more active
opposite

less, more

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Regulatory processes for glycogen synthase:
* Allosteric regulation: Binding of glucose 6-phosphate converts ____ form to ____ form. This conformational change favors ______ by protein phosphatase 1 (PP1).

Covalent regulation:
Insulin promotes ______ of glycogen synthase
Glucagon and epinephrine promote ________.

T, R
dephosphorylation
Glucose-6-phosphate is a positive affector of glycogen synthase

desphosphorylation
phosphorylation

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Glycogen breakdown:
______ is the regulatory enzyme.
Most active when ______.
Glycogen synthesis:
*_______ is regulatory enzyme.
Most _____ when phosphorylated.

Phosphorylase, phosphorylated

Glycogen synthase
inactive

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Phosphorylation of glycogen synthase by _____ to form glycogen synthase b _____ glycogen synthesis

protein kinase A
inhibits

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Protein phosphatase 1 (PP1) shifts glycogen metabolism from the ______ mode to the ______ mode.

degradation
synthesis

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Protein phosphatase 1 (PP1) _____ phosphoryl groups from phosphorylase kinase and phosphorylase a, inhibiting ________

removes glycogen degradation

PP1 removes phosphoryl groups from glycogen synthase ____, converting it into the more active ____ form.

b, a

Insulin also helps in regulation of these pathways, insulin inactivates _______ by ______ it

glycogen synthase kinase phosphorylating

Glycogen synthase kinase is an enzyme that ______ a _____ to glycogen synthase

adds, phosphate

PPP Yields ______ and _____ * ______ is typically carrier for ______ pathways (______ movement of electrons generally use ______) * _____ are pre-cursors for ______ 2. Glycolysis and PPP are ______ controlled.

NADPH, 5-C sugars NADPH, biosynthetic (building/synthesizing) Catabolic (breaking down), NADH 5-C sugars, nucleotides coordinately (control tied together) because G-6-P has multiple pathways

The first phase of the pentose phosphate pathway is the ______ generation of ______. Has ____ enzymatic steps The second phase is the _______ interconversion of a variety of sugars.

oxidative, NADPH, 3 enzymatic steps nonoxidative

The first reaction of the pentose phosphate pathway, the ________ of ________ by _______, is the _______ step of the pathway. The rate of the oxidative phase of the pentose phosphate pathway is controlled by the _______ _______ is the most important regulatory factor.

dehydrogenation glucose 6-phosphate glucose 6-phosphate dehydrogenase rate-limiting concentration of NADP+ [NADP+]

When ribose 5-phosphate needs exceed the needs for NADPH _____ will occur to get to G-3-P and ______ phase of PPP will occur to get ribose-5-phosphate

Glycolysis, non-oxidative

When NADPH and ribose 5-phosphate needs are balanced: the ______ phases of PPP occur and it stops after that

oxidative (ex. when cells are rapidly dividing)

When more NADPH is needed than ribose-5-phosphate: the _____ phase of PPP occurs, then the ribose-t-phosphate created is recycled back to make starting G-C-P through _____ phase

oxidative non-oxidative (ex. liver cells synthesizing fatty acids)

When both NADPH and ATP are required: ____ phase of PPP occurs and the ribose-5-phosphate created will undergo ______ phase to get metabolites to then make ATP through ______

oxidative non-oxidative glycolysis

_______ is the enzyme that controls the pentose phosphate pathway

Glucose-6-phosphate dehydrogenase

Fatty acid degradation, the activation and transfer of the ______ into the ______ and the _____ repetitive enzymatic steps of the _______ pathway.

acyl chain mitochondria four beta oxidation

Chylomicron particles are 98% _______ with ______ and ______ on the surface

triacylglycerols proteins, phospholipids Triacylglycerols need to be packaged into chylomicron to enter the bloodstream as they are NOT water soluble

Triacylglycerols in adipose tissue are converted into ______. This happens in response to hormonal signals that result in a series of ______ that activate the _____.

free fatty acids phosphorylations lipases

Lipase adds ______ to break ester linkages stepwise until it makes three fatty acids and ______.

water, glycerol

Glycerol is soluble in _____, carried to liver and converted to ______, which can enter ______ or ______

blood DHAP glycolysis, gluconeogenesis

Fatty acids are then transported out of fat cell into ______ and carried on a protein called ______

blood plasma albumin

The fatty acids incorporated into triacylglycerols in adipose tissue are made accessible in three stages. 1._______ to ______ fatty acids and glycerol into the blood for transport to energy-requiring tissues 2. ______ of the fatty acids and transport into the ______ for ______ 3. _______ of the ______ to acetyl CoA for processing by the citric acid cycle

Degradation of TAG, release Activation, mitochondria, oxidation Degradation, fatty acids, acetyl CoA

Fatty acid activation by acyl CoA synthetase ______ and ______ Driven by hydrolysis of _________

spontaneous irreversible pyrophosphate

Activated Fatty Acid must be _____ into mitochondria

ported Turned into acyl carnitine to go through mitochondria

Describe the repetitive steps of β oxidation

1) Oxidation (resulting in DB) 2) Hydration (Adding water, resulting in an -OH group) 3) Oxidation (C=O) 4) Thiolysis (adding CoA)

Enzymes for the repetitive steps of β oxidation

1) Oxidation (resulting in DB) - Acyl CoA dehydrogenase 2) Hydration (Adding water, resulting in an -OH group) - Enoyl CoA hydrotase 3) Oxidation (C=O) - 3-hydroxyacyl CoA dehydrogenase 4) Thiolysis (adding CoA) - Thiolase

The process is called β oxidation because its the ______ carbon that is being oxidized.

beta (second carbon away from carbonyl carbon)

Degradation of an unsaturated fatty acid requires one less _____ step because it already has that _______ that an ______ moves to put into the ______ configuration needed

oxidation double bond isomerase trans

* β Oxidation of fatty acids with odd numbers of carbons generates _______ in the last ______ reaction. * _______, a ______ enzyme, adds a ______ to propionyl CoA to form ________. * Succinyl CoA, a citric acid cycle component, is subsequently formed from methylmalonyl CoA by ________, a vitamin B12 -requiring enzyme.

propionyl CoA (3 carbon), thiolysis Propionyl CoA carboxylase, biotin, carbon, methylmalonyl CoA methylmalonyl CoA mutase

Formation of ketone bodies (______) Alternative route for _______ when have _____ glucose Occurs when excess buildup of _______ and not enough glucose to meet the energy needs of the organism Occurs in _____

ketogenesis acetyl CoA, low acetyl CoA liver mitochondria

3 primary products of ketogenesis:

Acetoacetate D-3-Hydroxybutyrate Acetone

Second step of ketogenesis is the control step, with the enzyme __________ that makes the 6-carbon structure Glucagon (low blood sugar) makes it _____ Insulin (high blood sugar) makes it _______

hydroxy methyl glutoryl CoA synthase speeds up slows down

Products of ketogenesis: D-3-Hydroxybutyrate is formed upon the _______ of acetoacetate. Acetone is generated by the spontaneous ________ of acetoacetate.

reduction decarboxylation

D-3-hydroxybutyrate can be considered a superior ketone body compared to acetoacetate because...

not only does it produce acetyl CoAs, it also makes NADH

_____ is the predominant fuel for the brain. * During starvation, ________ is initially the source of carbons for ________ 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 _______ as a fuel.

Glucose protein degradation, gluconeogenesis ketone bodies

Fatty acids represent a ______ energy source than carbohydrates because they generally yield more ______

richer ATP

Energy Yield from Oxidation of Fatty Acids * Each cycle of β-oxidation * 1 mole FADH2 * 1 mole NADH * Total: _______

(1.5 ATP) (2.5 ATP) Both can donate electrons to electron transport chain * Total: 4 ATP

* Acetyl-CoA enters citric acid cycle * 3 mole NADH (7.5 ATP) * 1 mole FADH2 (1.5 ATP) * 1 mole GTP (1 ATP) * Total: _______

10 ATP

Energy Yield from Oxidation of Stearic Acid * 8 rounds of β-oxidation * 8 x 4 ATP = 32 ATP * 9 moles acetyl-CoA * 9 x 10 ATP = 90 ATP * _________ of ATP to activate * Total: 32 + 90 – 2 = 120 ATP yield

-2 moles

1.The first stage of fatty acid synthesis is transfer of ______ out of the ______ into the ______. Citrate is transported into the cytoplasm and cleaved into oxaloacetate and acetyl CoA. 2. The second stage is the activation of _____ to form _______. 3. The third stage is the repetitive addition and reduction of _______ units to synthesize C 16 fatty acid. Synthesis occurs on an __________, a molecular scaffold.

acetyl CoA, mitochondria, cytoplasm acetyl CoA, malonyl CoA two carbon units, acyl carrier protein

Stage 2: The Formation of ______ Is the Committed Step in Fatty Acid Synthesis Malonyl CoA is synthesized from acetyl CoA by ______________, a biotin-requiring enzyme. The formation of malonyl CoA occurs in two steps

Malonyl CoA acetyl CoA carboxylase 1

________, a complex of enzymes, catalyzes the formation of fatty acids Fatty acid synthesis occurs on the _______, a polypeptide linked to the ________ group _______ and _______ attach substrates to the ______

Fatty acid synthase acyl carrier protein (ACP) phosphopantetheine group (Vit B5) Acetyl transacylase, malonyl transacylase

Acyl carrier protein is similar in structure to coenzyme A, but differs by having a _____ residue instead of _____

serine AMP

Fatty acid synthesis enzymes: 1) 2) 3) 4)

1) ketoacyl synthase (site for condensation, also has a docking site) 2) ketoacyl reductase 3) 3 hydroxyl dehydratase (water being removed, makes DB) 4) enoyl reductase (reduces the DB)

The ______ group is passed to the docking site of _______, allowing ACP to pick up _______

acetyl ketoacyl synthase malonyl group

_____ is the acyl group carrier for fatty acid oxidative degradation. ______ is the carrier for fatty acid synthesis

Coenzyme A Acyl carrier protein (ACP)

Mammals lack the enzymes that introduce double bonds from carbon _____, these need to be obtained in the ______

9 from the carbonyl diet

What Enzyme Regulates Fatty Acid Synthesis and Degradation? * Main regulation: _______ * Regulates both synthesis and beta-oxidation * ACC adds _______ group to acetyl CoA. * Forms activated starting material, _______ . * There are two isozymes of ACC: * Cytosolic (ACC1) – where ______ occurs * Mitochondrial (ACC2) – where _______ occurs * Both do same thing – synthesize malonyl CoA from acetyl CoA and bicarbonate

Acetyl CoA carboxylase (ACC) carboxylate malonyl CoA synthesis degradation

For each of these situations, would you want ACC1 (cystolic ACC) to be active? 1. The blood stream has a large concentration of fatty acyl-CoA (fatty acids bound to CoA) 2. High levels of insulin 3. The body has a large concentration of AMP 4. The body has build up of citrate

1. Slow synthesis, negative affector of ACC1 2. Indicates high blood glucose, activates ACC1 3. Indicates that body has energy needs, negative effector of ACC1 4. Means energy needs met, want ACC1 active, positive effector of synthesis

* When energy needs high: * glucagon and AMP high * Do not want to be ________ in this situation * High AMP activates AMPK active both inside and outside of mitochondria * AMPK acts on both ACC1 and ACC2 (phosphorylates them), which deactivates them. * When deactivated, shuts down synthesis of malonyl CoA both inside and outside the mitochondria * In cytosol: This means we shut down fatty acid synthesis (______ synthesis) * In matrix this means we can now transport fatty acids into the matrix for degradation, so beta-oxidation can begin to happen. (_______ degradation)

synthesizing fatty acids inhibits stimulates

Cholesterol has a complicated synthetic pathway (MANY steps) The regulatory enzyme of cholesterol synthesis is ____

HMG CoA Reductase

* Cholesterol and triacylglycerols are transported in the blood in the form of ______ particles. * Lipoprotein particles consist of a protein(s) component and various lipids, depending on the type of particle. * The protein(s) serve to _______ the lipids and to direct the particles to specific targets. * Lipoprotein particles are classified according to density: the greater proportion of lipid, the _____ dense the particle. * _______ is the major carrier of cholesterol in the blood. * High-density lipoprotein (HDL) carries cholesterol released into the blood back to the liver, a process called reverse cholesterol transport.

lipoprotein solubilize less (more TAG, less dense) Low-density lipoprotein (LDL)

Low-density lipoproteins deliver cholesterol to peripheral tissues. At the tissues, cholesterol enters the cell by receptor-mediated _______.

endocytosis

* Familial hypercholesterolemia: * genetic disease that results from the absence of the functional _______. * Studies of this disease have shed light on other, more common situation of _____ levels of cholesterol.

LDL receptor high No LDL receptor to pull cholesterol out of bloodstream, causing excess cholesterol to collect in various tissues of the body

Why is it essential that the mechanisms that activate glycogen synthesis also deactivate glycogen phosphorylase?

These two pathways occur in the same cellular compartment

It is advantageous that breakdown of glycogen gives rise to glucose-6-phosphate rather than to glucose because glucose-6-phosphate is already ______. This saves _____ equivalent in the early stages of glycolysis.

phosphorylated one ATP

Briefly outline the role of UDPG in glycogen biosynthesis. Each glucose residue is added to the growing glycogen molecule by transfer from ______.

UDPG

Glycogen synthase is subject to covalent modification and to allosteric control. The enzyme is _______ in its phosphorylated form and ______ when dephosphorylated. AMP is an allosteric ______ of glycogen synthase, whereas ATP and glucose-6-phosphate are allosteric ______.

active inactive inhibitor activators

There is a net gain of ______, rather than two, ATP when glycogen, not glucose, is the starting material of glycolysis.

three

You are planning to go on a strenuous hike and are advised to eat plenty of high-carbohydrate foods, such as bread and pasta, for several days beforehand. Suggest a reason for the advice. Eating high-carbohydrate foods for several days before strenuous activity is intended to build up _______ stores in the body. Glycogen will be available to supply required energy.

glycogen supply

What are four possible metabolic fates of glucose-6-phosphate?

Glucose-6-phosphate can be converted to glucose (gluconeogenesis), glycogen, pentose phosphates (pentose phosphate pathway), or pyruvate (glycolysis).

If a cell needs NADPH, ______ the reactions of the pentose phosphate pathway take place. If a cell needs ribose-5-phosphate, the ______ portion of the pathway can be bypassed; only the _______ reshuffling reactions take place. The pentose phosphate pathway does not have a significant effect on the cell’s supply of _____.

all oxidative, nonoxidative ATP

Acyl groups are esterified to ________ to cross the inner mitochondrial membrane.

carnitine

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

double bond, FAD NAD+

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

cis–trans isomerization

What are the unique enzymes needed to β-oxidize a monounsaturated fatty acid? For a monounsaturated fatty acid, an additional enzyme is needed, the __________.

enoyl-CoA isomerase

How many cycles of β-oxidation are required to process a fatty acid with 17 carbons?

It would take seven cycles of β-oxidation to release 14 carbons as acetyl-CoA, with the last three being released as propionyl-CoA.

Briefly outline the reactions involved in ketone production.

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

What is the metabolic importance of malonyl-CoA? It is a molecule that commits itself to fatty acid _______. It is also a potent inhibitor of carnitine acyltransferase I, thereby shutting down ________.

synthesis β-oxidation

How is ACP similar to coenzyme A? How is it different? Both have a ________ group at the active end. In coenzyme A, this group is attached to _______; in ACP, it is attached to a _______ of a protein.

phosphopantetheine -phospho-AMP serine residue

Carnitine functions as a ‘shuttle’ for our fatty acyl-CoA molecules to use in order to cross the mitochondrial membrane. The thioester bond on fatty acyls will be hydrolyzed to transfer the molecule onto the carnitine, which will then cross into the mitochondria where Coenzyme A will be ______ to the fatty acid to once again become ______ that can be subjected to _______.

re-attached fatty acyl CoA beta oxidation

Acetyl-CoA Carboxylase I: Malonyl-CoA is formed using biotin and ATP to fix ______ to ________, generating the _______ unit used to extend the fatty acid chain.

HCO3-, Acetyl-CoA 3-carbon

Transacylase: An acetyl-CoA or growing fatty acid chain is transferred to the acyl carrier protein (ACP), which then transfers it to ______. Malonyl-CoA is then transferred to _____.

ketoacyl synthase ACP

Ketoacyl Synthase Catalyzes a Claisen _______ between acetyl-CoA/FA chain and the malonyl group, releasing _____ in the process

condensation CO2

Ketoacyl Reductase ______ is used to reduce the carbonyl from the acetyl-CoA remnant to a hydroxyl group.

NADPH

Hydroxyacyldehydratase Catalyzes the dehydration of water between carbons 2 and 3, forming a new ______

C=C double bond

Enoyl Reductase NADPH is used to reduce the ________ formed in the previous step to a single bond. At this point, the ______ has successfully been added to the growing chain.

carbon-carbon double-bond acetyl-CoA

Steps in the repeating fatty acid synthesis cycle: Step 1 is a(n) _______, which results in a new, longer chain with two _______ bound to our ACP group. Step 2 is a(n) ______, which results in a(n) ______ group. Step 3 is a(n) ________, which results in a(n) _______ group. Step 4 is a(n) _______, which results in a(n) (n+2 ) fatty acid chain

condensation, carbonyls Reduction, hydroxyl Dehydration, alkene (C=C) Reduction

Explain why the formation of UDP-glucose in your body is generally considered irreversible and occurs in the direction of UDP-Glucose formation? The hydrolysis of ______ releases a _____ amount of free energy, which will drive the reaction forward enough to effectively make it irreversible.

pyrophosphate (PPi) large

What is the function of UDP-Glucose? UDP-glucose is the residue that is added to a growing glycogen chain. Upon being added to glycogen, you will have a glycogen molecule with ____ residues and a free _____ molecule.

(n+1) glucose UDP

Which enzyme is the primary enzyme for regulating cholesterol synthesis?

HMG-CoA reductase. This enzyme catalyzes the creation of mevalonate from HMG-CoA. It uses 2 NADPH.

HMG-CoA reductase is regulated at four levels:

1. Regulated at level of transcription: stimulating synthesis of mRNA needed to synthesize this protein 2. Regulated at level of translation: The rate of translation of the reductase mRNA is controlled by metabolites of mevalonate and dietary cholesterol. 3. Proteolytic degradation of the enzyme: Increases in cholesterol concentration result in the proteolytic degradation of the reductase. 4. Phosphorylation of the reductase by AMP-dependent kinase inactivates the enzyme.

State one common class of drugs used to treat high cholesterol and state how it works. Statins which are HMG-CoA reductase inhibitors. They are similar in structure to HMG-CoA and work to ______ inhibit HMG-CoA reductase by binding the enzyme at the active site.

competitively

Describe how VLDL that is released by the liver becomes LDL as it moves through the bloodstream.

Lipases break down fatty acids located in the VLDLs to move fatty acids into the cells. As this occurs more and more, the TAG content of these carriers decreases which will shift its composition to resemble that of LDL.

Describe the three steps of how LDL deliver cholesterol to peripheral tissues.

1) LDL will find and bind to an LDL receptor on a cell surface. 2) The LDL receptor will partake in endocytosis of the LDL molecule and bring this into the cell. 3) The LDL is hydrolyzed in lysosomes to release its content and the LDL receptor will float back to the cell surface to accept another LDL.

alpha-1,6-glucosidase releases ______

free glucose

Glycogenin generates the ______ needed for chain elongation

primer

Glycogen synthase catalyzes _______ of the glycogen chains

elongation

Phosphoglucomutase converts _______ to _________

glucose 1-phosphate, glucose 6-phosphate

Glycogen phosphorylase releases _______

glucose 1-phosphate

Which of the following are the two domains in the debranching enzyme involved in glycogen breakdown?

Transferase and a-1,6-glucosidase

Glucagon is associated with glycogen _______ and activates ______, which acts to ________ enzymes. Thus, in presence of glucagon, glycogen phosphorylase is ______ and _______, with the opposite being true of glycogen synthase.

breakdown, protein kinase A phosphorylate activated phosphorylated

The four repeated steps of fatty acid synthesis, in order, are _________.

condensation, reduction, dehydration, reduction

Week 13: Glycogen Synthesis, Pentose Phosphate Pathway, Fatty Acid and Lipid Metabolism Flashcards

(115 cards)