2.4 Gluconeogenesis

Question 1

What depends on glucose as their primary fuel and what relies on glucose as their only fuel?

Answer 1

Brain

RBCs

Question 2

Glycolysis, gluconeogenesis and glycogenolysis are regulated by

Answer 2

Insulin and glucagon

Question 3

What happens after a meal?

Answer 3

High blood glucose signals the pancreas to release insulin
(Tells muscles and adipose tissue to take up glucose)

Glycolysis and glycogenesis

Question 4

What happens during fasting?

Answer 4

Low blood glucose levels tells the pancreas to release glucagon

Question 5

What 2 major metabolic pathways function in the liver to maintain blood glucose levels at a steady state in order to feed the brain and RBCs?

Answer 5

Glycogenolysis and gluconeogenesis

Question 6

Define glycogenolysis

Answer 6

Breakdown of glycogen

Question 7

Define gluconeogenesis

Answer 7

Synthesis of glucose from non-carbohydrate precursors

Question 8

Describe a short fast

Answer 8

Utilizes glucose and breakdowns glycogens

Question 9

Describe overnight fast

Answer 9

Glycogen breakdown and gluconeogenesis

Question 10

Describe prolonged fast

Answer 10

• Breakdown of last remaining glycogen in the liver
• Gluconeogenesis becomes the sole source of glucose
• Lipolysis generates ketones for additional fuel
• Muscle protein is degraded for AA

Question 11

Major site of gluconeogenesis to supply blood glucose is the ___

Answer 11

liver

Question 12

What are the major precursors for gluconeogenesis?

Answer 12

Lactate
Glycerol
AA
TCA cycle intermediates

Question 13

Define glucogenic

Answer 13

Noncarbohydrate carbon substances that can be converted to pyruvate

Question 14

Examples of glucogenic

Answer 14

Lactate and alanine

Question 15

Catabolic rxns of fatty acids break off 2 carbon atoms at a time as acetyl-CoA which ___ be converted to glucose

Answer 15

Can’t

Question 16

An even number of fatty acids produces ___

Answer 16

Acetyl-CoA

Question 17

An odd number of fatty acids produces ___

Answer 17

Succinyl-CoA

FA off –> acetyl-CoA + single propionyl-CoA –> methylmalonyl-CoA –> succinyl-CoA

Question 18

Glycerol is ___

Answer 18

Glucogenic

Question 19

Gluconeogenesis is the reversal of glycolysis with 3 enzymatic exceptions:

Answer 19

• Conversion of pyruvate to PEP
• Conversion of F 1,6-biphosphate to F6P
• Conversion of G6P to Glucose

Question 20

How does gluconeogenesis start?

Answer 20

With the transport of pyruvate to the mitochondria and then its conversion to PEP

Question 21

What enzymes does pyruvate need to convert to PEP?

Answer 21

Pyruvate carboxylase
MT malate dehydrogenase
Cytosolic malate dehydrogenase
PEP carboxykinase

Question 22

What are the 2 different pathways for conversion of pyruvate to PEP?

Answer 22

Pyruvate (enters mitochondria) to oxaloacetate to malate (then leaves mitochondria) to oxaloacetate to PEP

Lactate to pyruvate (enters mitochondria) to oxaloacetate to PEP

Question 23

What does oxaloacetate convert into since it can’t directly cross the mitochondrial membrane?

Answer 23

Malate

Question 24

The choice between the 2 pathways for conversion of pyruvate to PEP depends on

Answer 24

Cytostolic NADH

Question 25

Conversion of Oxaloacetate to malate and malate to oxaloacetate yields what

Answer 25

NADH each

Question 26

Pyruvate to PEP conversion is regulated by what 2 different mechanisms?

Answer 26

PEP carboxykinase | Pyruvate carboxylase

Question 27

PEP carboxykinase expression is induced by ___ and inhibited by ___

Answer 27

Glucagon | Insulin

Question 28

Pyruvate carboxylase is ___ regulated by ___

Answer 28

Positively | Acetyl-CoA

Question 29

Once PEP is made and conditions favor gluconeogenesis, the enzymes of glycolysis can run in the opposite direction as far as

Answer 29

fructose-1,6-bisphosphate

Question 30

Fructose-1,6-bisphosphatase converts fructose-1,6-bisphosphate to

Answer 30

fructose 6-phosphate

Question 31

Fructose-2,6-bisphosphate is a ___ regulator

Answer 31

Allosteric

Question 32

Allosteric effectors of fructose-1,6-bisphosphatase are also allosteric effectors of

Answer 32

phosphofructokinase

Question 33

Interconversion of F6P to F-1,6-bisphosphate is regulated by __ via the production of ___

Answer 33

Insulin and glucagon | Fructose-2,6-bisphosphate

Question 34

Glucose-6-phosphatase dephosphorylates ___ to ___

Answer 34

G6P | Glucose

Question 35

___ is an integral membrane protein of the ER

Answer 35

Glucose-6-phosphatase

Question 36

Steps for glucose-6-P converting to glucose

Answer 36

1. Glucose-6-P is transported to ER lumen by a specific transporter 2. Glucose-6-P is hydrolyzed by glucose-6-phosphatase 3. Glucose is transported to cytosol via transporter T2 4. Transported out of cell via GLUT2

Question 37

Glucose is transported out of liver cells by

Answer 37

GLUT2

Question 38

A high AMP indicates that the energy charge is low and signals the need for ATP. This results in

Answer 38

glycolysis stimulation

Question 39

High ATP and citrate indicates that the energy charge is high and intermediates are abundant. This results in

Answer 39

Glycolysis inhibition

Question 40

___ is regulated indirectly by glucagon via ___

Answer 40

Pyruvate kinase | Protein Kinase A (PKA)

Question 41

Gluconeogenesis requires the input of ___ equivalents of ATP/GTP for each molecule of glucose

Answer 41

6 | 2 ATP needed by pyruvate carboxylase (2 GTP needed by PEP carboxykinase) (2 ATP needed by phosphoglycerate kinase)

Question 42

Gluconeogenesis requires how many NADH?

Answer 42

2

Question 43

Describe the cori cycle (lactic acid cycle)

Answer 43

- During high muscle activity the rate of glycolysis is faster than the rate of TCA cycle, so causes pyruvate to be converted to lactate - Lactate is sent to bloodstream and is used by liver as a gluconeogenic substrate

Question 44

Describe the alanine cycle (Cahill cycle)

Answer 44

- shuttles amino acid groups from the muscle to the liver for disposal as urea - Pyruvate from glycolysis is converted to alanine by alanine transaminase which is taken to liver where nitrogen enters the urea cycle and pyruvate undergoes gluconeogenesis

Question 45

The liver inhibits and stimulates what

Answer 45

Inhibits gluconeogenesis | Stimulates lipogenesis and glycogen synthesis

Question 46

Adipose tissue stimulate and inhibits what

Answer 46

Stimulates glucose uptake and lipogenesis | Inhibits lipolysis

Question 47

Striated muscle stimulates what

Answer 47

Glucose uptake, glycogen synthesis and protein synthesis

Question 48

Describe type I diabetes

Answer 48

Glucose stays in the blood because of the lack of insulin Insulin isn't released from pancreas Hyperglycemia Beta-cells are destroyed

Question 49

Describe type II diabetes

Answer 49

Pancreas releases insulin | Glucose remains in blood b/c tissues fail to respond to insulin

Question 50

Describe healthy glucose metabolism

Answer 50

Insulin is released by pancreas Glucose is removed by blood Insulin binds to insulin receptors