UNIT 4: REVIEW OF INTERMEDIARY METABOLISM

Question 1

Match the definitions with the terms:
1. “breakdown of stored glycogen to release glucose molecules”
2. “production of glucose from non-sugar substrates (lactate, glycerol, a.a.)”
3.
“glucose forms NADPH and ribose sugars”
4. “oxidation of glucose to pyruvate”
5. “production of glycogen granules from glucose”
6. “oxidize acetyl CoA to CO2”

Answer 1

1. Glycogenolysis
2. Gluconeogenesis
3. Hexose monophosphate shunt = pentose phosphate pathway
4. Glycolysis
5. Glycogenesis
6. Tricarboxylic acid cycle

Question 2

What are 3 fates of glucose?

Answer 2

Depending on the cell:

• glycogen
• glycolysis (to produce acetylCoA and fuel TCA cycle)
• pentose phosphates (for biogenesis)

Question 3

Glucagon is made in the ____ whereas Insulin is made in the _____.

Answer 3

Glucagon: alpha cells
Insulin: beta cells

…of the islets of pancreas

Question 4

What tissues make glycogen?

What is the content of glycogen in each tissue?

Answer 4

liver and muscle
- liver stores 10% of wet weight
- muscle 1%
BUT 75% of glycogen is in muscle (because more muscle

Question 5

What triggers glycogen synthesis?

Answer 5

Presence of G6P (accumulation)

Question 6

What 2 enzymes are involved in glycogen synthesis (glycogenesis)?

Answer 6

Hexokinase and Glucokinase

Question 7

What is the role of hexokinase?

Answer 7

Hexokinase is in the muscle
- allosterically inhibited by high glucose 6
phosphate
- free glucose builds up inside muscle
- since hexokinase cannot convert glucose to G6P
- stops glucose being transferred from blood to muscle (since build up of glucose in muscle)

Question 8

What is the role of glucokinase?

Answer 8

in the liver

• NOT inhibited by G6P, liver cells continue to phosphorylate free glucose (from blood stream)to G6P
• build up of G6P, satisfies hexose monophosphate shunt, to process G6P to acetyl CoA (glycolysis)
• removed from liver as VLDL particles made de novo fatty acids and triglycerides

Question 9

The muscle takes up glucose _____ , while liver takes up glucose _____.

Answer 9

Muscle: based on needs
Liver: continuously/ongoing removing glucose from blood stream

Question 10

How many high energy phosphates are expended per glucose to be stored as glycogen?

Answer 10

2 Phosphates

1. ATP used. Glucose (in blood) —> G6P in muscle (via hexokianse) or liver (glucokinase)
2. Glucose 1 Phosphate reacts with UTP to form UDP-glucose (Pi released). UDP-glucose bond can release enough energy to add glucose to form glycogen chain.

Question 11

What protein does glycogen synthesis start on?

Answer 11

glycogenin

Question 12

What’s the difference between a-1-4 and a-1-6 links?

Answer 12

Glycogen links.
a-1-4 chain is linear
a-1-6 chain is at branched points.

(too much branching = increase volume = very dense sphere = glycogen granule)

Question 13

What happens to glycogen in glycogenolysis?

Answer 13

• glycogen is converted to G1P in liver or muscle, then G6P

- G6P then converts to glucose in blood OR lactate in blood to liver

Question 14

What is the fate of G6P in glycogenolysis?

Answer 14

Liver: G6P released to blood stream because of glucose6phosphatase in the SER
Muscle: G6P is fully oxidized to CO2 or converted to lactate

Question 15

What happens to lactate that comes from the muscle from glycogenolysis?

Answer 15

Lactate is taken up by liver and converted back to glucose. (Therefore, muscle plays an indirect role in contributing to blood glucose)

Question 16

Substrate level phosphorylation occurs in:

a. glycolysis
b. TCA
c. ETC

Answer 16

Substrate level phosphorylation occurs in both a. glycolysis and b. TCA

ETC is oxidative phosphorylation

Question 17

What are the products of glycolysis?

Answer 17

• Net: 2ATP
• 2 pyruvate
• 2 NADH

Question 18

When does pyruvate form acetyl-coa and how?

Answer 18

• Aerobic conditions: in the presence of O2

- pyruvate dehydrogenase activity

Question 19

What causes muscle pain in anaerobic conditions?

Answer 19

Lactate production increases H+ ions that increase metabolic acidosis and decreases muscle contractility.

Question 20

Under anaerobic conditions, NAD+ is regenerated by…

Answer 20

converting pyruvate to lactate

Question 21

Under anaerobic conditions how is glucose regenerated?

Answer 21

lactate is sent to the liver and converted to glucose via gluconeogenesis (Cori Cycle)

Question 22

Is the Cori Cycle energy producing or energy using?

Answer 22

Energy using.
In the liver, Lactate to Glucose (gluconeogenesis)
- requires 6ATP per 2 molecules of lactate to form 1 glucose
- 1 glucose produces 2 ATP
- not sustainable under intense exercise

Question 23

Where does the hexose monophosphate shuttle take place?

Answer 23

Cytosol

- uses G6P as substrate

Question 24

What are the two possible routes of the HMPS?

Answer 24

• oxidative phase

- non-oxidative phase

Question 25

What do each of the two phases of HMPS produce?

Answer 25

Oxidative phase: produces ribulose-5-phosphate

Non-oxidative phase: ribose-

Question 26

In the oxidative phase, what is the purpose of the redox couple in HMPS?

Answer 26

HMPS is the major pathway that maintains the reduced state NADPH in the NADP+/NADPH.

• reducing power is used for anabolism and oxidant defense

Question 27

_____ acts as a strong reducing agent for oxidant defense.

Answer 27

NADPH

- anabolic metabolism

Question 28

How is pyruvate converted to acetyl CoA?

Answer 28

Pyruvate Dehydrogenation via pyruvate dehydrogenase complex

Question 29

Pyruvate Dehydrogenation is important because it converts pyruvate (3C) to acetyl CoA (2C). The type of metabolism changes from ____ to _____.

Answer 29

Glucogenic to Ketogenic

Question 30

What are the 4 cofoactors involved in pyruvate dehydrogenation?

Answer 30

• Pantothenic acid as CoA
• Thiamine as TPP
• Niacin as NAD+
• Riboflavin as FAD

Question 31

What are the products of pyruvate dehydrogenation?

Answer 31

• acetyl CoA
• CO2
• NADH

Question 32

What are the 2 TCA inputs?

Answer 32

• acetyl CoA

- oxaloacetate

Question 33

From 6C citrate to 4C succinyl-CoA how many electrons are captured?

Answer 33

4 electrons as 2 NADH

• C released as CO2

Question 34

From 4C succinyl coA what happens as it is reverted back to oxaloacetate?

Answer 34

• GTP
• FADH2
• NADH
  produced

Question 35

TCA cycle is also the starting place for ______

Answer 35

gluconeogenesis or de novo synthesis of glucose

Question 36

What is the molecule that is gluconeogenic/glucogenic?

Answer 36

malate

- if malate can be transported out of mitochondria, then all other intermediaries can be removed

Question 37

Compare and contrast Glucogenic vs Ketogenic molecules in TCA.

Answer 37

Glucogenic: converted to TCA intermediate, removed when forming malate converted to glucose
Ketogenic: elongates existing intermediate but does not produce new intermediates and does not produce glucose

Question 38

de novo synthesis of glucose from non-glucose precursors is called

Answer 38

Gluconeogenesis

Question 39

Where does gluconeogenesis occur?

Answer 39

in the liver

start: mitochondria
end: cytosol

(reverse glycolysis)

Question 40

What molecules can be the starting point for gluconeogenesis?

Answer 40

any metabolite that can enter TCA as a new intermediate

• alpha keto acids (pyruvate, glutamate, oxaloacetate)
• lactate
• glycerol

Question 41

What happens to malate when it leaves the TCA cycle?

Answer 41

• Malate leaves the mitochondria
• Oxaloacetate in cytosol
• Oxaloacetate converted to PEP and reverse glycolysis

Question 42

Why can’t ketogenic molecules be glucogenic?

Answer 42

acetyl coA only elongates the TCA cycle, it does not provide extra TCA intermediates