Lecture 16: Glycolysis and Gluconeogenesis

Question 1

In the mouth, _______\______\__ breaks α1,4 bonds forming dextrans

Answer 1

In the mouth, Salivary​ amylase breaks α1,4 bonds forming dextrans

Question 2

_______________: cleaves α1,4 bonds, products maltose, isomaltose, tri and oligosaccharides

Answer 2

Pancreatic α-amylase: cleaves α1,4 bonds, products maltose, isomaltose, tri and oligosaccharides

Question 3

_______\_ cleaves α1,6 bond of branched oligosaccharides

Answer 3

Isomaltase cleaves α1,6 bond of branched oligosaccharides

Question 4

α-glucosidase/_____\_ cleave non-reducing ends of oligosaccharides and α1,4 bond of maltose to produce glucose monomers

Answer 4

α-glucosidase/maltase cleave non-reducing ends of oligosaccharides and α1,4 bond of maltose to produce glucose monomers

Question 5

________\_–converts sucrose to glucose + fructose

Answer 5

Sucrase–converts sucrose to glucose + fructose

Question 6

_____\_ -converts lactose to glucose + galactose

Answer 6

Lactase -converts lactose to glucose + galactose

Question 7

Insulin _______ glucose while glucagon, adrenaline, cortisol ______ plasma glucose levels

Answer 7

Insulin reduces glucose while glucagon, adrenaline, cortisol increase plasma glucose levels

Question 8

Failure to maintain normal glucose levels above ___________results in __________\_(shortage of glucose to the brain) and can result in loss of consciousness, brain damage, and death.

Answer 8

Failure to maintain normal glucose levels above 3-3.5mmol/L results in neuroglycopenia(shortage of glucose to the brain) and can result in loss of consciousness, brain damage, and death.

Question 9

Insulin _________\_ target proteins

Glucagon ________\_ target proteins

Answer 9

Insulin dephosphorylates target proteins

Glucagon phosphorylates target proteins

Question 10

________ and ________ cells are only two cell types that have insulin responders

_________ sucks up more insulin

Answer 10

Muscle and Adipose cells are only two cell types that have insulin responders

Muscle sucks up more insulin

Question 11

The liver uses _________ for the synthesis of fatty acids for triglyceride

–active in fed state (insulin) and inactivated in fasting state (glucagon)

Answer 11

The liver uses glycolysis for the synthesis of fatty acids for triglyceride

–active in fed state (insulin) and inactivated in fasting state (glucagon)

Question 12

Metabolic Fuels for various cells/tissues

• RBC -can only utilize ______________\_
• Muscle –oxidizes glucose and stores ______\_. Can switch to FA oxidation during fasting.
• Adipose tissue –takes up glucose and fatty acids where they are converted to TAGs and stored. Can utilize FAs as a fuel source during fasting.
• Liver –utilizes FA oxide during fasting

Excess glucose can be converted to the ________ molecule of triacylglycerol

Acetyl CoA from glycolysis can form the substrate for de novo lipogenesis

Answer 12

Metabolic Fuels for various cells/tissues

• RBC -can only utilize glucose/anaerobic glycolysis
• Muscle –oxidizes glucose and stores glycogen. Can switch to FA oxidation during fasting.
• Adipose tissue –takes up glucose and fatty acids where they are converted to TAGs and stored. Can utilize FAs as a fuel source during fasting.
• Liver –utilizes FA oxide during fasting

Excess glucose can be converted to the Glycerol molecule of triacylglycerol

Acetyl CoA from glycolysis can form the substrate for de novo lipogenesis

Question 13

Metabolic Activity During Fasting

• Heart preferentially utilizes _________\_
• Adipose undergoes lipolysis –released fatty acids converted to ketones by the liver. _______\_ used for gluconeogenesis
• Liver -maintains blood glucose by gluconeogenesis (4-6h after) fasting) or glycogenolysis (induced 2-3h after fasting). The liver cannot utilize ________ for energy purposes
• Muscle releases amino acids during fasting for _________\_. Utilizes fatty acids and ketones for its own fuel source.
• Brain can switch from using glucose to ketone bodies during prolonged fasting –does this to spare muscle wasting. The brain cannot utilize fatty acids as they don’t cross the BBB

Answer 13

Metabolic Activity During Fasting

• Heart preferentially utilizes fatty acids
• Adipose undergoes lipolysis –released fatty acids converted to ketones by the liver. Glycerol used for gluconeogenesis
• Liver -maintains blood glucose by gluconeogenesis (4-6h after) fasting) or glycogenolysis (induced 2-3h after fasting). The liver cannot utilize ketone bodies for energy purposes
• Muscle releases amino acids during fasting for gluconeogenesis. Utilizes fatty acids and ketones for its own fuel source.
• Brain can switch from using glucose to ketone bodies during prolonged fasting –does this to spare muscle wasting. The brain cannot utilize fatty acids as they don’t cross the BBB

Question 14

Glycolysis is the breaking down of glucose. _______ a three-carbon carboxylic acid is the end product of glycolysis (2 moles of pyruvate formed per 1 mole of glucose)

Answer 14

Glycolysis is the breaking down of glucose. Pyruvate a three-carbon carboxylic acid is the end product of glycolysis (2 moles of pyruvate formed per 1 mole of glucose)

Question 15

Glucose is converted into a storage carbohydrate known as glycogen in a process called __________\_. ________\_ is the production of glucose 6-phosphate by splitting a glucose monomer from glycogen by adding an inorganic phosphate whereas _________\_ is the metabolic process by which glucose is formed from non-carbohydrate precursors in the _______.

Answer 15

Glucose is converted into a storage carbohydrate known as glycogen in a process called glycogenesis. Glycogenolysis is the production of glucose 6-phosphate by splitting a glucose monomer from glycogen by adding an inorganic phosphate whereas gluconeogenesis is the metabolic process by which glucose is formed from non-carbohydrate precursors in the liver.

Question 16

Glucose is taken up into erythrocytes and brain via _____\_ (insulin-independent) transporter

Glucose taken up into beta cells via _____\_ on the liver and beta cells stimulates insulin secretion.

Glucose is taken up into adipocytes and muscle cells in response to insulin via the __________\_

Answer 16

Glucose is taken up into erythrocytes and brain via GLUT1 (insulin-independent) transporter

Glucose taken up into beta cells via GLUT2 on the liver and beta cells stimulates insulin secretion.

Glucose is taken up into adipocytes and muscle cells in response to insulin via the GLUT4 transporter

Question 17

Aerobic glycolysis/respiration –pyruvate reduced completely to CO2 and H20 in cells possessing mitochondria and sufficient oxygen (______ATP)

Anaerobic glycolysis/respiration –pyruvate reduced to lactic acid (___ ATP)

Answer 17

Aerobic glycolysis/respiration –pyruvate reduced completely to CO2 and H20 in cells possessing mitochondria and sufficient oxygen (36-38 ATP)

Anaerobic glycolysis/respiration –pyruvate reduced to lactic acid (2 ATP)

Question 18

Pyruvate Kinase Deficiency is responsible for ________\_

Answer 18

Pyruvate Kinase Deficiency is responsible for hemolytic anemia

• Varies significantly in severity –little intervention to transfusion requirements
• RBCs are broken down prematurely resulting in anemia–gathered by spleen resulting in enlargement of the spleen

Question 19

In order to replenish NAD+ (an important oxidizing agent that accepts electrons from other molecules and is reduced) in the cell, pyruvate is reduced to lactate by the enzyme ___________\_ under anaerobic conditions. Most lactate in blood is retrieved by the liver and used as a substrate for gluconeogenesis

Answer 19

In order to replenish NAD+ (an important oxidizing agent that accepts electrons from other molecules and is reduced) in the cell, pyruvate is reduced to lactate by the enzyme lactate dehydrogenase under anaerobic conditions. Most lactate in blood is retrieved by the liver and used as a substrate for gluconeogenesis

Question 20

Normal ranges of lactate in blood <2mmol/s, values above 4-5mmol/L indicative of __________\_ often a result of hypoxia

Answer 20

Normal ranges of lactate in blood <2mmol/s, values above 4-5mmol/L indicative of Lactic Acidosis ​often a result of hypoxia

Question 21

_____________\_ –found in most tissues but is Glucokinase the liver

• Provides glucose-6-phosphate for ATP production
• Experiences auto-feedback inhibition by its product glucose-6-phosphate, but not so in the liver. Why?

Answer 21

Hexokinase –found in most tissues but is glucokinase the liver

• Provides glucose-6-phosphate for ATP production
• Hexokinase experiences auto-feedback inhibition by its product glucose-6-phosphate (Not glucokinase as phosphorylation of glucose is also important for glucose storage as glycogen and for the generation of acetyl CoA from glucose as a building block for de novo lipogenesis)

Question 22

_____________:

• Found in liver and pancreas. Very active after a meal but inactive during periods of fasting.
• Induced by insulin and not inhibited by glucose-6-phosphate

Answer 22

Glucokinase:

• Found in liver and pancreas. Very active after a meal but inactive during periods of fasting.
• Induced by insulin and not inhibited by glucose-6-phosphate

Question 23

Pyruvate kinase-

• Activated by _____ 1,6 bisphosphate and inhibited by alanine and by _______\_ in the liver during fasting when glucagon is high
• Inhibition of pyruvate kinase results in switch towards __________\_
• Activated in the fed state/insulin by _____________\_

Answer 23

Pyruvate kinase –active in its dephosphorylated form

• Activated by fructose 1,6 bisphosphate and inhibited by alanine and by phosphorylation in the liver during fasting when glucagon is high (PKA)
• Inhibition of pyruvate kinase results in switch towards gluconegogenesis
• Activated in the fed state/insulin by dephosphorylation (phosphatases)

Question 24

Phosphofructokinase-1 (PFK-1)

• _________ regulator of glycolysis
• Activity varies according to the energy status of the cell
• ATP is a substrate and an _________ of PFK-1
• AMP ________ PFK1 –important in uscle during exercise when AMP levels increase and ATP decreases

Answer 24

Phosphofructokinase-1 (PFK-1)

• Positive regulator of glycolysis
• Activity varies according to the energy status of the cell
• ATP is a substrate and an Inhibitor of PFK-1
• AMP Activates PFK1 –important in muscle during exercise when AMP levels increase and ATP decreases

Question 25

Precursors to Gluconeogenesis?

Answer 25

Lactate, Amino Acids (Alanine), and Glycerol

Question 26

_Cori Cycle/ Lactic Acid Cycle_: * Cycle by which lactic acid released by muscle after glycolysis is reconverted in the liver back to glucose and recycled back to the muscle * Lactate converted to pyruvate by \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ * Pyruvate is then used as a substrate for \_\_\_\_\_\_\_\_\_\_\_\_\_\_

Answer 26

_Cori Cycle/ Lactic Acid Cycle_: * Cycle by which lactic acid released by muscle after glycolysis is reconverted in the liver back to glucose and recycled back to the muscle * Lactate converted to pyruvate by _lactate dehydrogenase (LDH)_ * Pyruvate then used as a substrate for _gluconeogenesis_

Question 27

Alanine converted to pyruvate by \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ Following deamination, the carbons of amino acids are converted to \_\_\_\_\_\_\_ Amino groups converted to \_\_\_\_\_\_\_\_

Answer 27

Alanine converted to pyruvate by **alanine aminotransferase** (ALT) Following deamination, the carbons of amino acids are converted to **Glucose** Amino groups converted to **Urea**

Question 28

\_\_\_\_\_\_\_\_\_\_is the only organ capable of utilizing **glycerol** produced by the degradation of triglycerides by hormone-sensitive lipase.

Answer 28

**_The Liver_** is the only organ capable of utilizing glycerol produced by the degradation of triglycerides by hormone-sensitive lipase.

Question 29

\_\_\_\_\_\_\_\_\_\_, which is expressed in the liver, phosphorylates glycerol to glycerol phosphate

Answer 29

**Glycerol kinase**, which is expressed in the liver, phosphorylates glycerol to glycerol phosphate

Question 30

Mutases catalyze the transfer of functional groups within a molecule

Answer 30

**_Mutases_** catalyze the transfer of functional groups within a molecule

Question 31

***\_\_\_\_\_\_\_\_\_\_\_\_\_\_** –oxidises a substrate by reducing an electron acceptor (NAD+/NADP+/FAD)*

Answer 31

***_Dehydrogenase_** –oxidises a substrate by reducing an electron acceptor (NAD+/NADP+/FAD)*

Question 32

\_\_\_\_\_\_\_\_\_\_: * Involved in the ________ of pyruvate to oxaloacetate, acetyl-CoA to malonyl-CoA and propionyl-CoA to methylmalonyl-CoA * Is a CO2 carrier on the surface of the carboxylase enzyme and is necessary for numerous conversions * Excessive ingestion of avidin (which is found in egg whites) has been associated with its deficiency.\

Answer 32

_Biotin_: * Involved in the **_Carboxylation_** of pyruvate to oxaloacetate, acetyl-CoA to malonyl-CoA and propionyl-CoA to methylmalonyl-CoA * Is a CO2 carrier on the surface of the carboxylase enzyme and is necessary for numerous conversions * Excessive ingestion of avidin (which is found in egg whites) has been associated with its deficiency.\

Question 33

Pyruvate (3C) converted to oxaloacetate (4C) by \_\_\_\_\_\_\_\_\_\_, a mitochondrial enzyme that requires ATP and ______ as a cofactor

Answer 33

Pyruvate (3C) converted to oxaloacetate (4C) by _Pyruvate Carboxylase_, a mitochondrial enzyme that requires ATP and _Biotin_ as a cofactor

Question 34

\_\_\_\_\_\_\_\_\_\_ –adds CO2 –anabolic/building up -require biotin/ATP \_\_\_\_\_\_\_\_\_\_ –removing CO2 –catabolic/breaking down

Answer 34

**_Carboxylase_** ***–***adds CO2 –anabolic/building up -require biotin/ATP **_Decarboxylases_** ***–***removing CO2 –catabolic/breaking down

Question 35

First committed Step of Glycolysis?

Answer 35

**Step 3:** Fructose-6-phosphate is phosphorylated by **phosphofructokinase**(PFK) to form fructose 1,6 bisphosphate

Question 36

In a fed state, insulin levels rise and induce phosphatases that _____________ (**PFK2**) that becomes a kinase that converts Fructose-6-Phosphate to Fructose-2,6-BisPhosphate. Fructose-2,6-BisPhosphate then activates **PFK1** which leads to _______ glycolysis and _______ gluconeogenesis

Answer 36

In a fed state, insulin levels rise and induce phosphatases that **_Dephosphorylate_** (**PFK2**) which converts Fructose-6-Phosphate to Fructose-2,6-BisPhosphate. Fructose-2,6-BisPhosphate then activates **PFK1** which leads to **_Increased**_ glycolysis and _**Decreased_** gluconeogenesis

Question 37

In a fasted state, glucagon levels rise _______ is activated and phosphorylates PFK2 which becomes a phosphatase. F-2-6-BisPhosphate is then converted to Fructose-6-Phosphate → levels of fructose-2,6-Bisphosphate fall → PFK1 less active→ _______ glycolysis and _________ gluconeogenesis

Answer 37

In a fasted state, glucagon levels rise **_PKA-cAMP_** is activated and phosphorylates PFK2 which becomes a phosphatase F-2-6-P is then converted to Fructose-6-Phosphate→levels of fructose-2,6-Bisphosphate fall →PFK1 less active→ **_Decreased**_ glycolysis and _**Increased_** gluconeogenesis

Question 38

* Dephosphorylated PFK2 = \_\_\_\_\_\_(Adds or removes phosphate groups?)* * Phosphorylated PFK2 = \_\_\_\_\_\_\_(Adds or removes phosphate groups?)*

Answer 38

Dephosphorylated PFK2 = **_Kinase_ (Adds phosphate groups)** Phosphorylated PFK2 = **_Phosphatase_ (Removes phosphate groups)**

Question 39

Several tissues use triglyceride breakdown products as intermediates in energy generation and glucose synthesis. Which of the following is a liver-specific enzyme that facilitates such reactions? A.Acyl CoA synthetase B.Glycerol kinase C.Glucose-6-phosphate dehydrogenase D.Acetyl CoA carboxylase E.ATP-citrate lyase

Answer 39

Several tissues use **triglyceride breakdown** products as intermediates in **energy generation and glucose synthesis**. Which of the following is a **liver-specific enzyme** that facilitates such reactions? A.Acyl CoA synthetase **B.Glycerol kinase** C.Glucose-6-phosphate dehydrogenase D.Acetyl CoA carboxylase E.ATP-citrate lyase

Question 40

A 78-year old female suffers from nausea, anorexia, fatigue and skin rash on her legs. She is mildly demented and is believed to have **severe malnutrition**. Laboratory findings include **lactic acidosis**. You suspect that **biotin deficiency** may contribute to this patient’s symptoms. Which of the following conversions is impaired in those with biotin deficiency? A.Pyruvate to alanine B.Pyruvate to oxaloacetate C.Glucose to ribose-5-phosphate D.Pyruvate to acetyl-CoA E.Succinate to oxaloacetate

Answer 40

A 78-year old female suffers from nausea, anorexia, fatigue and skin rash on her legs. She is mildly demented and is believed to have **severe malnutrition**. Laboratory findings include **lactic acidosis**. You suspect that **biotin deficiency** may contribute to this patient’s symptoms. Which of the following conversions is impaired in those with biotin deficiency? A.Pyruvate to alanine **B. Pyruvate to oxaloacetate** C.Glucose to ribose-5-phosphate D.Pyruvate to acetyl-CoA E.Succinate to oxaloacetate

Question 41

\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_: * Enzyme responsible for cleavage of glucose-6-phosphate to glucose * This glucose can now be secreted into circulation * Enzyme important for both ________ **and \_\_\_\_\_\_\_**

Answer 41

**_Glucose-6-phosphatase_** * Enzyme responsible for cleavage of glucose-6-phosphate to glucose * This glucose can now be secreted into circulation * Enzyme important for both **_gluconeogenesis_ and _glycogenolysis_**

Question 42

Regulation of Gluconeogenesis in the Liver

Answer 42