Chapter 9: Carbohydrate Metabolism: Glycolysis, Glycogen, Gluconeogenesis, and the Pentose Phosphate Pathway Flashcards by Maria Tolosa

How many glucose transporters are there?

4 - GLUT 1 through 4

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GLUT ____ is a low-affinity transporter in hepatocytes and pancreatic cells.

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After a meal, blood traveling through the ____________ ________ vein from the intestine is rich in glucose. GLUT ____ captures the excess glucose primarily for storage.

hepatic portal; 2

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What is K_{m_?}

The concentration of substrate when an enzyme is active at half of its maximum velocity

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The lower the K_{m_{, the higher is what?}}

the enzyme’s affinity for the substrate

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When the glucose concentration drops below the K_{m_{for the transporter, much of the remainder of glucose does what?}}

Bypasses the liver and enters the peripheral circulation

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The K_{m_{is quite high - what does this mean?}}

The liver will pick up glucose in proportion to its concentration in the blood.

i.e. The liver will pick up excess glucose and store it preferentially after a meal, when blood glucose is high

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In the beta-islet cells of the pancreas, GLUT ____, along with the glycolytic enzyme ____________, serves as the glucose sensor for insulin release.

2; glucokinase

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GLUT ____ is in adipose tissue and muscle and responds to the glucose concentration in peripheral blood.

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The rate of glucose transport in adipose and muscle is increased by ________, which stimulates the movement of additional GLUT ____ transporters to the membrane by a mechanism involving exocytosis.

insulin; 4

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The K_{m_{of GLUT4 is close to the normal glucose levels in blood. This means that the transporter is saturated when?}}

When the blood glucose levels are just a bit higher than normal

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How do cells with GLUT4 transporters increase their intake of glucose?

Increase the number of GLUT 4 transporters on their surface

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Although basal levels of transport occur in all cells independently of insulin, the ________ rate increases in ________ tissue and ________ when insulin levels rise.

transport; adipose, muscle

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Muscle stores excess glucose as ____________, and adipose tissue requires glucose to form dihydroxyacetone phosphate (DHAP), which is converted to ____________ ____________ to store incoming fatty acid as ________________.

glycogen, glycerol phosphate, triacylglycerols

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All cells can carry out glycolysis. In a few tissues, specifically ____ ________ ________, glycolysis represents the only energy yielding pathway available because they lack mitochondria, which are required for TCA, ETC, oxidative phosphorylation, and fatty acid metabolism (beta-oxidation).

red blood cells

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________ is the major monosaccharide that enters the glycolysis pathway, but others like ____________ and ____________ can also feed into it.

glucose; galactose and fructose

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Glycolysis is a cytoplasmic pathway that converts ____________ into 2 ____________ molecules. This releases ____________ captured in 2 substrate-level ________________ and 1 ____________ reaction.

glucose; pyruvate
phosphorylations; oxidation

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If a cell has mitochondria and oxygen, the energy carriers produced in glycolysis, ________, can feed into the ________ ____________ pathway to generate energy for the cell.

NADH; aerobic respiration

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If either mitochondria or oxygen is lacking, like in RBCs or exercising skeletal muscle, then glycolysis can happen ________________, although some available energy is lost.

anaerobically

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Glycolysis also provides ________________ for other pathways, e.g. in the liver, glycolysis is part of the process in which excess ________ is converted to fatty acids for storage.

intermediates; glucose

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Glucose enters the cell by ____________ diffusion or ________ transport. The enzyme ____________ (or ____________ in the liver) convert glucose to ____________ ____-____________.

facilitated, active; hexokinase, glucokinase; glucose 6-phosphate

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Hexokinase is found where? What inhibits it?

Widely distributed in tissues and inhibited by glucose 6-phosphate

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Glucokinase is only found in ________ cells and ____________ (beta-islet) cells. It is induced by ________________.

liver, pancreatic; insulin

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Hexokinase has a ____ Km, meaning it reaches max velocity at a ____ [glucose].

low; low

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Glucokinase has a ____ Km, meaning it acts on glucose proportionally to its concentration.

high

________________-____ is the **rate limiting enzyme** and main control point in glycolysis.

phosphofructokinase-1

Phosphofructokinase-1 phosphorylates ____________ ____-____________ to ____________ ____-____________ using ________.

fructose 6-phosphate to fructose-1,6 bisphosphate using ATP

PFK-1 is inhibited by ____ and ________, and activated by ____.

ATP and citrate; AMP

Why is PFK-1 inhibited by ATP and citrate?

ATP - because glycolysis is off when the cell has sufficient energy (high ATP) Citrate - high levels imply cell is producing enough energy

________ stimualtes and ____________ inhibits PFK-1 in hepatocytes.

Insulin; glucagon

Insuling activates ________________-____, which converts ____________ ____-________ to ____________ ____-____________.

phosphofructosekinase-2; fructose 6-phosphate to fructose 2,6-bisphosphate

What activates PFK-1?

F26BP

____________ inhibits PFK-2, which lowers ____________, which ultimately inhibits PFK-1.

F26BP; glucagon

________ is found mostly in the liver. By activating PFK-1, it allows cells to do what?

PFK-2; allows cells to keep doing glycolysis even if the cell is satisfied, that way the metabolites can be used for production of glycogen, fatty acids, and other storage molecules, rather than just be used for ATP production

What enzyme catalyzes the oxidation and addition of Pi to glyceraldehyde 3-phosphate?

glyceraldehyde-3-phosphate dehydrogenase

Once glyceraldehyde 3-phosphate is phosphorylated, it produces what high-energy intermediate? What is also reduced?

1,3-bisphosphoglycerate; NAD+ to NADH

If glycolysis is aerobic, the NADH reduced by glyceraldehyde-3-P dehydrogenase can be used for what?

Oxidized by the mitochondrial ETC to provide energy for ATP synthesis by oxidative phosphorylation

____-____________ ________ transfers the high-energy phosphate from ____-____________ to ADP, which forms what two things?

3-phosphoglycerate kinase; 1,3-bisophosphoglycerate; ATP and 3-phosphoglycerate

Pyruvate kinase phosphorylates ADP using ________________. It is activated by what enzyme?

phosphoenolpyruvate; F16BP

Without oxygen, ____________ will occur. The key enzyme here is ____________ ________________.

fermentation; lactate dehydrogenase

Lactate dehydrogenase oxidizes ________ to ________, replenishing the oxidized coenzyme for ________________-____-____ ________________.

NADH to NAD+, glyceraldehyde-3-phosphate dehydrogenase

Without mitochondria and oxygen, glycolysis would stop when all the available ________ has been reduced to ________. By reducing pyruvate to ________ and oxidizing NADH to NAD+, lactate dehydrogenase prevents this problem.

NAD+, NADH; lactate

________________ ________ (DHAP) is used in hepatic and adipose tissue for ____________ synthesis. It is formed from what?

dihydroxyacetone phosphate; fructose 1,6-bisphosphate

DHAP can be isomerized to ________ ____-________, which can then be converted to ____________, the backbone of triacylglycerols.

glycerol 3-phosphate; glycerol

Which two intermediates are used to generate ATP by substrate-level phosphorylation? These are the only ATP gained in anaerobic respiration.

1. 1,3-bisphosphoglycerate 2. phosphoenolpyruvate

Which 3 enzymes catalyze reactions that are irreversible in glycolysis?

1. glucokinase or hexokinase 2. PFK-1 3. pyruvate kinase

In RBCs, ____________ glycolysis is the only pathway for ATP production, yielding a net ____ ATP per glucose.

anaerobic; 2

RBCs have ________________ ________, which produces ____-________ from ____-________ in glycolysis.

bisphosphoglycerate mutase; 2,3-BPG from 1,3-BPG

What do mutases do?

Move a functional group from one place in a molecule to another (in this case phosphate)

____-________ binds allosterically to the beta-chains of hemoglobin A and ____________ its affinity for oxygen.

2,3-BPG, decreases

An important source of galactose is ____________.

lactose

Lactose is hydrolyzed to galactose and glucose by ____________.

lactase

Once transported into tissues, galactose is phosphorylated by ________________.

galactokinase

Galactose 1-phosphate is converted to ____________ ____-________ by ____________ and what enzyme?

glucose 1-phosphate; epimerase, galactose-1-phosphate uridyltransferase

Epimerases are enzymes that catalyze the conversion of what to what?

One sugar epimer to another

Epimers are ____________ that differ where?

Diastereomers, differ at exactly 1 chiral carbon

Galactokinase does what?

Phosphorylates galactose to galactose 1-phosphate (ATP to ADP)

________ is found as part of the disaccharide sucrose.

Fructose

The liver phosphorylates fructose using ____________ to trap it in the cell.

fructokinase

Once fructose is phosphorylated into fructose 1-phosphate, it is cleaved into ________________ and ________ by what enzyme?

glyceraldehyde, DHAP; aldolase B

Pyruvate from ____________ glycolysis enters mitochondria, where it may be converted to ________-________ for entry into the cirtic acid cycle IF ATP is needed, or for ________ ________ synthesis if sufficient ATP is present.

aerobic; acetyl-CoA; fatty acid

The ____________ ________________ ________ reaction is irreversible and cannot be used to convert acetyl-CoA to pyruvate or to glucose.

pyruvate dehydrogenase complex

Pyruvate dehydrogenase in the liver is activated by ____________, whereas in the nervous system, the enzyme is not responsive to hormones. This makes sense because high insulin levels signal to the liver that the individual is what?

insulin; well-fed

When well-fed, the liver should not only burn glucose for energy, but shift the fatty acid equilibrium toward what instead of what?

production/storage instead of oxidation

What are the 3 possible fates of pyruvate?

1. conversion to acetyl-CoA by pyruvate dehydrogenase 2. conversion to lactate by lactate dehydrogenase 3. conversion to oxaloacetate by pyruvate carboxylase

Pyruvate dehydrogenase is inhibited by what?

Its product, acetyl-CoA

Glycogen stored in the liver is mobilized when? How about muscle glycoen?

Between meals to prevent low blood sugar; for muscle contraction

Plants also store excess glucose in long alpha-linked chains of glucose called ____________.

starch

____________ is the synthesis of glycogen granules. It begins with a core protein called ____________.

glycogenesis; glycogenin

Glucose addition in glycogenesis begins with ____________ ____-____________, which is converted to ____________ ____-________.

glucose 6-phosphate to glucose 1-phosphate

Glucose 1-phosphate is activated by coupling to a molecule of ____________ ________________, which permits its integration into the glycogen chain by ________________ ____________.

uridine diphosphate; glycogen synthase

Glucose 1-phosphate's activation occurs when it interacts with ____________ ____________ to form UDP-glucose and a ________________.

uridine triphosphate; pyrophosphate

____________ ____________ is the rate-limiting enzyme of glycogen synthesis.

Glycogen synthase

What inhibits glycogen synthase?

Epinephrine and glucagon

____________ ____________ is responsible for introducing alpha-1,6-linked branches into the glycogen granule as it grows.

branching enzyme

________________ is the process of breaking down glycogen using what enzyme?

Glycogenolysis; glycogen phosphorylase

In contrast to a hydrolase, a phosphorylase breaks bonds using what instead of what?

inorganic phosphate, water

Glycogen phosphorylase breaks what type of bonds and releases what?

alpha-1,4 glycosidic bonds, releases glucose 1-phosphate

Glycogen phosphorylase is activated by ____________ in the liver, so that glucose can be provided for the rest of the body. In skeletal muscle ,it is activated by ________ and ____________, which signal that the muscle is active and requires more glucose. It is inhibited by ________.

glucagon; AMP and epinephrine; ATP

Debranching enzyme is a 2-enzyme complex that deconstructs the branches in glycogen that have been exposed by what enzyme?

glycogen phosphorylase

The liver maintains glucose levels in blood during fasting through either ____________ or ________________.

glycogenolysis or gluconeogenesis

What promotes glycogenolysis and gluconeogenesis?

1. Glucagon 2. Epinephrine

What inhibits gluconeogenesis and glycogenolysis?

Insulin

Glucogenic amino acids (except leucine and lysine) can be converted into intermediates that feed into ________________, while ketogenic amino acids can be converted into ____________ ____________, an alternative fuel.

gluconeogenesis; ketone bodies

Pyruvate carboxylase is a mitochondrial enzyme activated by ____________-________. The product, ________________, is a citric acid cycle intermediate that cannot leave the mitochondrion. Instead, it is reduced to ____________, which can then leave.

acetyl-CoA; oxaloacetate, malate

Once in the cytoplasm, malate can be oxidized to ________________.

oxaloacetate

____________________ ________________ is induced by glucagon and cortisol, which generally act to raise blood sugar levels. It converts OAA to PEP in a reaction that requires ________.

phosphoenolpyruvate carboxykinase; GTP

________________________ in the cytoplasm is a key control point of gluconeogenesis and represents the rate-limiting step of the process. It reverses the action of PFK-1 (the rate limiting step of ____________) by removing phosphate from F16BP to produce F6P.

fructose-1,6-bisphosphatase; glycolysis

F16BP is activated by ____ and inhibited by ____ and ________.

ATP; AMP, F26BP

____________________ is found only in the lumen of the ER in liver cells.

glucose 60phosphatase

What are the 2 major functions of the pentose phosphate pathway?

1. produce NADPH 2. produce **ribose 5-phosphate** for nucleotide synthesis

PPP begins with ____________ ____-____________, ends with ____________ ____-____________, and is irreversible

glucose 6-phosphate, ribulose 5-phosphate

The production of ribulose 5-phosphate produces ________ and involves an important rate-limiting enzyme, what is it?

NADPH; glucose-6-P dehydrogenase

In the cell, ________ acts as a high-energy electron acceptor. It is a potent oxidizing agent (and reduces itself in the process).

NAD+

________ produced from the reduction of NAD+ can then feed into the ETC to indirectly produce ________.

NADH, ATP

Conversely, ____________ primarily acts as an electron donor in a number of biochemical reactions. It is a potent reducing agent (and is oxidized itself during the process).

NADPH