A&P 400 - Metabolism 2

Define Glycogenesis:

*Glucose Storage* as glycogen: ■ Polysaccharide that is only stored carb in humans ■ If glucose is not needed immediately to form ATP, many glucose molecules will combine to form *glycogen*

What is *Proton Motive Force:*

*Potential energy gradient* formed by *Hydrogen ions in space b/w outer & inner mitochondrial membranes*

ATP generation in Kreb's cycle is oxidative or substrate level phosphorylation:

*Substrate level* Phosphorylation

What is the net gain of ATP after Glycolysis?

- consumes 2 x ATP + generates 4 x ATP = *net gain of 2 ATP*

What are the only 2 types of tissue that can store glycogen?

-*Skeletal Muscle* (75% of all glycogen) -*Liver Hepatocytes* (25% of all glycogen)

How many steps are involved with the Krebs Cycle?

8 Steps

What is the net outcome of the Krebs Cycle?

For *2 x Acetyl CoA* ■ 6 x NADH ■ 2 x FADH2 ■ 2 x ATP ■ 4 x CO2 (waste)

Decarboxylation

The loss of a molecule of CO2 by a substance.

What stimulates Gluconeogenesis?

*-Glucagon* *-CORTISOL*

What stimulates hepatocytes and skeletal muscle cells to turn glycogen back to glucose to use for energy (glycogenolysis)?

*-Glucagon* -Epinephrine

What non-carbohydrate carbon substrates are used in Gluconeogenesis? (what NOT?)

*-Glycerol* *-Lactic acid* *-Amino acids* *(NOT Fatty Acid => Know this!)*

In the electron transport chain, how many ATP will a molecule of FADH2 produce?

*1.5*

What else is generated during Glycolysis?

*2 x NADH* (coenzyme)

In the electron transport chain, how many ATP will a molecule of NADH produce?

*2.5*

How many oxygen molecules are used during the complete oxidation of one glucose molecule? a. 2 b. 4 c. 6 d. 8

*6* Correct answer is: c. 6

What is Chemiosmosis:

*ATP generated* as *H+ moves back into cell* from the Proton Motive Force

Name of enzyme that synthesizes ADP to ATP at end of Electron Transport Chain during Chemiosmosis:

*ATP synthase*

What are the 8 stages of the Krebs Cycle?

*CIA/Secret Service For Mr. Obama* *1. Citric Acid* *2. Isocitric Acid* 3. Alpha-Ketoglutaric Acid 4. Succinyl CoA 5. Succinic Acid 6. Fumaric Acid 7. Malic Acid 8. Oxalocetic Acid (REMEMBER AT LEAST 2 FOR MARK)

Where does glycolysis take place exactly?

*Cytosol* of the cell

Define Glycogenolysis:

*Glucose Release* from glycogen ■ Glycogen stored in hepatocytes and skeletal mm released to be used for energy

Where is the Electron Transport Chain located?

*Inner* Mitochondrial Membrane

Where does Gluconeogenesis take place?

*Liver (Hepatocytes)*

Is the process for Glycogen release from hepatocytes and skeletal mm the same?

*NO* ■ Glycogen stored in hepatocytes (25%) broken down into *glucose and released into blood* ■ Glycogen stored in skeletal mm (75%) converted to *Glucose-6-Phosphate* & enters *Glycolysis* (step 2) => Acetyl CoA stage => Krebs cycle => Electron Transport Chain

The synthesis of ADP to ATP in electron transport chain is an example of Substrate-Level Phosphorylation or Oxidative Phosphorylation?

*Oxidative* Phosphorylation

The synthesis of ADP to ATP in Glycolysis is an example of Substrate-Level Phosphorylation or Oxidative Phosphorylation?

*Substrate-Level* Phosphorylation (Cytosol)

T/F; all glucose that enters a skeletal mm cell, will be used in that cell and will never be released as glucose?

-*True* -Phosphatase is absent in skeletal mm cells -Glycogen is broken down into glucose 1-phosphate, which is then catabolized for ATP production via glycolysis and the Krebs cycle. -However, the lactic acid produced by glycolysis in mm cells can be converted to glucose by the liver. (-All glucose that enters skeletal mm cell, stays and is either used for energy or stored as glycogen)

-What will the electron transport chain later yield of the 3 NADH + 3 H+? -What will the electron transport chain yield of the FADH2?

-7.5 ATP molecules (2.5 ATP per NADH) -1.5 ATP molecules -Each "turn" of the Krebs cycle eventually generates 9 molecules of ATP -B/c each glucose molecule provides 2 acetyl CoA molecules, electron transport chain yields 18 molecules of ATP per glucose molecule.

Glycolysis overview -All of the 10 steps are catalyzed by unique ________________ (same ingredients in different shapes with phosphates added) -All in all, created _______ ________________ molecules + net ______ ____________ -There is one ___________ ___________ enzyme, which is the only one we need to know about

-All of the 10 steps are catalyzed by unique *enzymes* (same ingredients in different shapes with phosphates added) -All in all, created *2 NADH* molecules + net *2 ATP* -There is one *rate limiting* enzyme, which is the only one we need to know about

Carbon Dioxide

-CO2 liberated as pyruvic acid converted to acetyl CoA -Liberated during decarboxylation reactions in Krebs cycle -B/c each glucose generates two pyruvic acid molecules, six CO2 liberated from each original glucose molecule catabolized along this pathway -The CO2 molecules diffuse out of the mitochondria, through the cytosol and plasma membrane, and then into the blood. Blood transports CO2 to the lungs, where it is eventually exhaled.

How much ATP does glycolysis produce? -Consumes ______ ATP but generates ______ -> NET GAIN of ______ ATP for each glucose molecule that is ____________ -First 5 steps __________ ______ ______ and increases the ____________ ____________ in the molecules (uses ___ ATP) -Steps 6-10 is where _______ ATP are ____________

-Consumes *2* ATP but generates *4* -> NET GAIN of *2* ATP for each glucose molecule that is *oxidized* -First 5 steps *uses the ATP* and increases the *potential energy* in the molecules (uses 2 ATP) -Steps 6-10 is where *4* ATP are *generated*

In *Aerobic* environment, what happens to Pyruvic Acid once it enters the Mitochondrial Matrix?

-Converted to *Acetyl Coenzyme A* aka: Acetyl CoA

Overall, what is produced for every one Acetyl CoA that enters the Krebs cycle?

-For every ONE acetyl CoA that enters the Krebs cycle, 3 NADH + 3H+, and 1 FADH2 is produced -One molecule of ATP generated by substrate-level phosphorylation

What are the steps in conversion of Pyruvic Acid to Acetyl CoA:

-Pyruvic Acid converted to* 2-Carbon Acetyl Group* by an enzyme -1 x CO2 removed as waste -Acetyl group attaches to Coenzyme A to form *Acetyl Coenzyme A*

Formation of Acetyl Coenzyme A

-The coenzyme used at this point in cellular respiration is called *coenzyme A (CoA)* (derived from panthtenic acid, a B vitamin) -During this transitional step between glycolysis and Krebs cycle, pyruvic acid is prepared for entrance into the cycle -An enzyme found in mitochondrial matrix (pyruvate dehydogenase) converts pyruvic acid to a 2-carbon fragment called an *acetyl group* by removing a molecule of CO2 -First reaction in cellular respiration to release CO2 -Pyruvic acid is also oxydized: *Each pyruvic acid loses 2 hydrogen ions (in form of one hydroxide ion H- and one hydrogen ion H+) *The coenzyme NAD+ is reduced as it picks up H- from pyruvic acid; the H+ is released into mitochondrial matrix *i.e. NAD+ is reduced to NADH + H+ -Recall that the oxidation of one glucose molecule produces two molecules of pyruvic acid, so for each molecule of glucose, two molecules of CO2 are lost and two NADH + H+ are produced. -The acetyl group attaches to coenzyme A, producing a molecule called *acetyl coenzyme A (acetyl CoA)*

Phosphofructokinase -The enzyme that catalyzes step _____ of _____________ and is the key regulator of _____________. -It is _____________ _____________ because it is the _____________ of all 10 of the steps; the reaction can only happen as quickly as this step does. -This enzyme is used in step _____ which is when _____________ _____-_____________ is converted to _____________ ____, ____-_____________

-The enzyme that catalyzes step *3* of *glycolysis* and is the key regulator of *glycolysis*. -It is *rate limiting* because it is the *slowest* of all 10 of the steps; the reaction can only happen as quickly as this step does. -This enzyme is used in step *3* which is when *Fructose 6-phosphate* is converted to *Fructose 1, 6-bisphosphate*

1. What is the net gain of ATP from skeletal mm or nerve cells? 2. Other body cells?

1. 30 x ATP 2. 32 x ATP

Chemiosmosis 1. Energy from ____________ + ____________ passes along the electron transport chain and is used to pump ____________ from the ____________ of the mitochondrion into the space between the ____________ and ____________ ____________ ____________. This mechanism is called a ____________ ____________ because ____________ ions consist of a single ____________. 2. A high concentration of ____________ accumulates between the ___________ and ____________ ____________ ____________ (_______________ ______________ created) NOTE: gradient has a potential energy called ____________ ____________ ____________ 3. ____________ ____________ then occurs as hydrogen ions flow back into the ____________ ____________ through a special type of H+ channel in the inner membrane. NOTE: this step involves the use of ____________ ____________

1. Energy from *NADH + H+* passes along the electron transport chain and is used to pump *H+* from the *matrix* of the mitochondrion into the space between the *inner* and *outer mitochondrial membranes*. This mechanism is called a *proton pump* because H+ ions consist of a single *proton*. 2. A high concentration of *H+* accumulates between the *inner* and *outer mitochondrial membranes* (electrochemical gradient created) NOTE: gradient has a potential energy called *proton motive force* 3. *ATP synthesis* then occurs as hydrogen ions flow back into the *mitochondrial matrix* through a special type of H+ channel in the inner membrane. NOTE: this step involves the use of *ATP synthase*

What are the stages of Glucose catabolism aka: Cellular Respiration:

1. Glycolysis 2. Formation of Acetyl Coenzyme A 3. Krebs Cycle 4. Electron Transport Chain

There are 2 possible outcomes for Pyruvic Acid. What variable decides the outcome?

1. Lack of Oxygen *(Anaerobic) = Conversion to Lactic Acid*, difuse out of cell and travel to Liver 2. Presence of Oxygen *(Aerobic) = Pyruvic Acid mvmt into Mitochondrial Matrix* for next step in catabolism of glucose

How many steps are involved w/ Glycolysis?

10 steps 10 reactions (to get from 6-carbon glucose to two 3-carbon pyruvic acids)

How many steps are involved in the conversion of Pyruvic Acid to Acetyl CoA in the Mitochondria?

2 Steps

CO2 in the Krebs cycle

2 decarboxylation reactions release CO2 CO2 will diffuse out of cell and will be carried to the lungs

What is the *end product* of Glycolysis?

2 x *Pyruvic Acid* molecules

Total end products of Glycolysis =

2 x Pyruvic Acid 2 x ATP (mm & nn => 0 x ATP) 2 x NADH

How many proton pump "carriers" are utilized during the electron transport chain?

3

How many carbons are in a molecule of Glucose?

6-carbons C-C-C-C-C-C

Formation of acetyl coenzyme A A _____________ step that prepares _____________ _____________ for entrance into the _____________ _____________. This step also produces energy-containing _____________ plus _____________.

A *transition* step that prepares *pyruvic acid* for entrance into the *Krebs cycle*. This step also produces energy-containing *NADH + H+* plus *CO2*.

Glycolysis A set of _____________ in which one _____________ molecule is _____________ and two molecules of _____________ _____________ are produced. The reaction also produces two molecules of ___________ and two energy-containing _____________.

A set of *reactions* in which one *glucose* molecule is *ozidized* and two molecules of *pyruvic acid* are produced. The reaction also produces two molecules of *ATP* and two energy-containing *NADH + H+*.

When is the activity of Phosphofructokinase high? Low?

Activity of this enzyme is high when ADP concentration is high, in which case ATP is produced rapidly. When the activity of phosphofructokinase is low, most glucose does not enter the reactions of glycolysis but instead undergoes conversion to glycogen for storage.

Is the Krebs Cycle Aerobic or Anaerobic?

Aerobic

What does each step of oxidation of glucose require?

An enzyme and often a coenzyme

How do red blood cells produce ATP?

Because they lack mitochondria, red blood cells can only produce ATP through glycolysis.

What is the purpose of Glycolysis?

Breakdown Glucose: C-C-C-C-C-C into *2 x Pyruvic Acid:* C-C-C + C-C-C

What happens to all the NADH & FADH2 generated during the 1st 3 stages of Glucose Catabolism?

Enter the Electron Transport Chain

What happens to Acetyl CoA once produced in Mitochondria?

Enters the Krebs Cycle aka: Citric Acid Cycle

Glucose Anabolism

Even though most of the glucose in the body is catabolized to generate ATP, glucose may take part in or be formed via several anabolic reactions. One is the synthesis of gycogen; another is the synthesis of new glucose molecules from some of the products of protein and lipid breakdnwn.

*Net* products after conversion of Pyruvic Acid into Acetyl Coenzyme A?

For *2 x Pyruvic Acid* ■ 2 x CO2 (waste) ■ 2 x NADH ■ 2 x Acetyl CoA *THERE IS NO ATP GENERATED*

Glycogenolysis

Glycogenolysis is not a simple reversal of the steps of glycogenesis. IT begins by splitting glucose molecules off the branched glycogen molecule via phosphorylation to form glucose 1-phosphate. Phosphorylase, the enzyme that catalyzes this reaction, is activated by *glucagon* from pancreatic alpha cells and epinephrine from the adrenal medulla. Glucose 1-phosphate is then converted to glucose 6-phosphate and finally to glucose, which leaves hepatocyetes via glucose transporters (GlutT) in the plasma membrane. Phosphorylated glucose molecules cannot ride aboard the GlutT transporters, so the enzyme *phosphatase* converts glucose 6-phosphate into glucose.

What is the difference between glycogenolysis and glycolysis?

Glycogenolysis is the breakdown of glycogen to glucose. Glycolysis is the 10 reactions that convert glucose to pyruvic acid.

What happens to Lactic Acid in the liver?

Hepatocytes convert back to Pyruvic Acid

What happens to pyruvic acid if oxygen is plentiful? If oxygen is plentiful (aerobic conditions), most cells convert pyruvic acid to ____________ ____________ ______. This molecule links ____________, which occurs in the ____________, with the ____________ ____________, which occurs in the ____________ _______ ____________. Pyruvic acid enters the ____________ ____________ with the help of a special ____________ ____________.

If oxygen is plentiful (aerobic conditions), most cells convert pyruvic acid to *acetyl coenzyme A*. This molecule links *gylcolysis*, which occurs in the *cytosol*, with the *Krebs cycle*, which occurs in the *matrix of mitochondria*. Pyruvic acid enters the *mitochondrial matrix* with the help of a special *transporter protein*.

What happens to pyruvic acid if oxygen is scarce? If oxygen is scarce (anaerobic conditions) - for example, in _____________ ______________ fibers during ______________ ______________ - then pyruvic acid is reduced via an _____________ ______________ by the addition of two ______________ atoms to form _____________ _____________ (______________) 2 pyruvic acid + 2NADH + 2H+ -> 2 lactic acid and 2 NAD+ The ______________ is used in step ________ of glycolysis. As ______________ ______________ is produced, it quickly diffuses ________ _______ ________ _________ and enters the ______________ to travel to the ______________.

If oxygen is scarce (anaerobic conditions) - for example, in *skeletal muscle* fibers during *strenuous exercise* - then pyruvic acid is reduced via an *anaerobic pathway* by the addition of two *hydrogen* atoms to form *lactic acid (lactate)* 2 pyruvic acid + 2NADH + 2H+ -> 2 lactic acid and 2 NAD+ The *NAD+* is used in step *6* of glycolysis. As *lactic acid* is produced, it quickly diffuses *out of the cell* and enters the *blood* to travel to the *liver*. Hepatocytes can convert lactic acid back to pyruvic acid.

What does insulin do?

It stimulates hepatocytes and skeletal muscle cells to synthesize & store glycogen. (driving force)

Where does the Krebs Cycle take place?

Mitochondrial Matrix

What does the electron transport chain need?

NADH

Does glycolysis require oxygen?

NO. It is a way to produce ATP anaerobically --> and therefore it is AKA *anaerobic cellular respiration*

Is there any CO2 produced during Glycolysis?

No (Anaerobic process)

Once the ______________ ______________ has undergone ______________ and the remaining acetyl group has attached to ______________, the resulting compound (acetyl CoA) is ready to enter the ______________ ______________.

Once the *pyruvic acid* has undergone *decarboxylation* and the remaining acetyl group has attached to *CoA*, the resulting compound (acetyl CoA) is ready to enter the *Krebs cycle*.

What happens to glucose in Red Blood Cells?

Only goes through glycolysis, no mitochondria to allow further steps.

Electron Transport Chain reactions -Oxidize what (2) and does what with what?

Oxidize NADH + H+ and FADH2 and transfer their electrons through a series of electron carriers.

Krebs Cycle reactions -Oxidize what (1) and produce what (4)?

Oxidize acetyl coenzyme A and produce CO2, ATP, NADH + H+, and FADH2

What is the overall purpose of the Krebs cycle?

Production of NADH and FADH2 for use in Electron Transport Chain

What enzyme converts Pyruvic Acid to 2-Carbon Acetyl group?

Pyruvate Dehydrogenase

What are the most important outcome of the Krebs cycle?

Reduced coenzymes (NADH and FADH2) are the most important outcome (they contain the energy originally stored in glucose and then inpyruvic acid)

In what step is Phosphofructokinase used during Glycolysis?

Step 3

What are the Krebs cycle and Electron Transport Chain collectively known as?

The Krebs cycle and electron transport chain both require oxygen to produce ATP and are collectively known as *aerobic cellular respiration*

What does the conversion of NADH + H+ and FADH2 to ATP?

The electron transport chain

The Electron Transport Chain The electron transport chain is a series of ____________ ____________, integral membrane proteins in the inner ____________ ____________. This membrane is folded into christae that increase its surface area, accommodating thousands of copies of the transport chain in each mitochondria. Each carrier in the chain is ____________ as it picks up electrons and ____________ as it gives up electrons. As electrons pass through the chain, a series of ____________ reactions release small amounts of energy; this energy is used to form ____________. In aerobic cellular respiration, the final electron acceptor of the chain is ____________. Because this mechanism of ATP generation links ____________ ____________ (the passage of electrons along transport chain) with the pumping of ____________ ions, it is called ____________.

The electron transport chain is a series of *electron carriers*, integral membrane proteins in the *inner mitochondrial membrane*. This membrane is folded into christae that increase its surface area, accommodating thousands of copies of the transport chain in each mitochondria. Each carrier in the chain is *reduced* as it picks up electrons and *oxidized* as it gives up electrons. As electrons pass through the chain, a series of *exergonic* reactions release small amounts of energy; this energy is used to form *ATP*. In aerobic cellular respiration, the final electron acceptor of the chain is *oxygen*. Because this mechanism of ATP generation links *chemical reactions* (the passage of electrons along transport chain) with the pumping of *hydrogen* ions, it is called *chemiosmosis*.

What does the fate of pyruvic acid depend upon?

The fate of pyruvic acid produced during glycolysis depends on the availability of oxygen.

What is the point of cellular respiration?

The production of ATP

The Krebs Cycle The reactions occur in the ______________ of the ______________ and consist of a series of ______________-______________ reactions and ______________ reactions that release ______________. In the Krebs cycle, the oxidation-reduction reactions transfer ______________ ______________, in the form of ______________, to two coenzymes -- ______________ and ______________. The pyruvic acid derivatives are ______________, and the coenzymes are ______________. In addition, one step generates ______________.

The reactions occur in the *matrix of the mitochondria* and consist of a series of *oxidation-reduction* reactions and *decarboxylation* reactions that release *CO2*. In the Krebs cycle, the oxidation-reduction reactions transfer *chemical energy*, in the form of *electrons*, to two coenzymes -- *NAD+ and FAD*. The pyruvic acid derivatives are *oxidized*, and the coenzymes are *reduced*. In addition, one step generates *ATP*.

In *muscle & nerve cells*, what happens to the net 2 x ATP after glycolysis?

They are consumed when moving NADH into Mitochondria (Electron Transport Chain) *= net gain of 0 x ATP*

What happens when there is no glucose readily available and body activities require ATP?

When body activities require ATP, glycogen stored in hepatocytes is broken down into glucose and released into the blood to be transported to cells, where it will be catabolized via cellular respiration.

How much glycogen can the body store?

about 500g (approx 1 lb)

Define Gluconeogenesis:

metabolic pathway that results in generation of glucose from non-carbohydrate carbon substrates (non-sugar => sugar)

What is the Electron Transport Chain?

❑ Series of electron carriers where each carrier is reduced and oxidized as it passes along electrons, creating a *Proton Motive Force* ❑ As electrons pass through chain, exergonic reactions release energy which is used to form ATP (Chemiosmosis) ❑ *Final electron acceptor is OXYGEN* to form water