Gluconeogenesis

Question 1

Mobilization of liver glycogen stores helps to maintain adequate glucose supply, but these storescan
be fully depleted in

Answer 1

24 hours

Question 2

The synthesis of new glucose from simple carbon-­skeleton precursors,
also helps maintain bloodglucose levels, and can serve this function for up to several weeks

Answer 2

Gluconeogenesis

Question 3

Occurs not only during periods of extended fasting/starvation, but at all times

Answer 3

Gluconeogenesis

Question 4

Critical for the clearance of blood lactate produced by tissues and cells performing anaerobic glycolysis, such as rapidly exercising muscle and RBCs

Answer 4

Gluconeogenesis

Question 5

Most of the bodies gluconeogenesis occurs in the

Answer 5

Liver

Question 6

Can contribute up to 10% of the body’s gluconeogenesis but only in the later stages of a fast

Answer 6

Kidneys

Question 7

Not able to perform gluconeogenesis, though it provides important substrates for this process

Answer 7

Muscle

Question 8

Requires chemical energy in the form of ATP and NADH

Answer 8

Gluconeogenesis

Question 9

Are able to perform gluconeogenesis even during the lean times of an extended fast because they are simultaneously also able to oxidize fatty acids for the production of ATP and NADH

Answer 9

Liver and Kidney

Question 10

The metabolic conditions that call for accelerated gluconeogenesis include the mobilization of fatty acids for

Answer 10

Catabolism

Question 11

Several compounds may contribute their carbon skeletons to glucose synthesis. These include all the glycolytic and TCA cycle intermediates with the significant exception of

Answer 11

Acetyl CoA

Question 12

18 of the 20 amino acids, as well as a few other compounds such as propionate and glycerol can also contribute their carbon skeletons to

Answer 12

Gluconeogenesis

Question 13

The product of anaerobic glycolysis, produced in tissues during periods of high energy demand but low oxygen supply

Answer 13

Lactate

Question 14

Also produced in specialized cells which lack mitochondria, such as RBCs

Answer 14

Lactate

Question 15

Summarizes the principal means by which lactate is cleared from the body

Answer 15

The Cori Cycle

Question 16

Reversible depending on the concentration of pyruvate and lactate, and the NADH/NAD+ ratio

Answer 16

The lactate dehydrogenase reaction

Question 17

The oxidation of lactate occurs in the cytoplasm and produces

Answer 17

Pyruvate and NADH/H+

Question 18

Two moles of lactate are recruited for the formation of

Answer 18

One mole of glucose

Question 19

Pyruvate is then transported into mitochondria where we see the first reaction unique to

Answer 19

Gluconeogenesis

Question 20

Our goal is the production of

-can not be produced by reversing the pyruvate kinase reaction

Answer 20

Phosphoenolpyruvate (PEP)

Question 21

The first gluconeogenic ‘detour’ is a two-­step process, beginning with the conversion of pyruvate to the TCA cycle intermediate oxaloacetate (OAA) by

Answer 21

Pyruvate carboxylase

Question 22

CO2 and ATP are required in this reaction, and a critical cofactor for pyruvate carboxylase is

Answer 22

Biotin

Question 23

The conversion of pyruvate to oxaloacetate by pyruvate carboxylase is stimulated by high levels of

Answer 23

Mitochondrial acetyl CoA

Question 24

Muscle tissues lack the enzyme

Answer 24

Pyruvate carboxylase

Question 25

Oxaloacetate cannot be transported across the mitochondrial membrane, so,it is carried across the mitochondrial membrane by either

Answer 25

Malate or aspartate

Question 26

Conversion of malate to OAA produces NADH, therefore whether OAA uses malate or aspartate shuttle depends on the need for reducing equivalents in the

Answer 26

Cytosol

Question 27

Used to convert 1,3- | bisphosphoglycerate to glyceraldehydes 3-­phosphate during gluconeogenesis

Answer 27

NADH

Question 28

Cytoplasmic oxaloacetate is then converted to PEP by

Answer 28

PEP-carboxykinase

Question 29

The formation of PEP-carboxykinase 1. ) Consumes 1? 2. ) Releases 1?

Answer 29

1. ) GTP | 2. ) CO2

Question 30

Each of the first two reactions unique to gluconeogenesis are driven energetically by the hydrolysis of a high energy

Answer 30

Phosphodiester bond

Question 31

This makes these reactions

Answer 31

Irreversible

Question 32

We now take advantage of five consecutive reversible reactions of glycolysis to convert two moles of PEP into one mole of

Answer 32

Fructose 1,6-bisphosphate

Question 33

Along the way we consume another pair of ATP molecules with the conversion of two moles of 3-­phosphoglycerate to

Answer 33

1,3-bisphosphoglycerate

Question 34

The conversion of two moles of 3-phosphoglycerate to 1,3-bisphosphoglycerate consumes another pair of ATP molecules. This reaction is catalyzed by

Answer 34

3-phosphoglycerate kinase

Question 35

In the next reaction, catalyzed by glyceraldehyde 3-phosphate dehydrogenase, we oxidize the -produced in the original oxidation of lactate

Answer 35

NADH/H+

Question 36

With fructose 1,6-bisphosphate we return to a familiar area in glycolysis, and to the highly regulated enzyme

Answer 36

PFK-1

Question 37

That reaction, with the consumption of an ATP, is irreversible, so a second detour is taken with the gluconeogenic enzyme

Answer 37

Fructose 1,6-bisphosphatase-1 (FBP-1)

Question 38

This enzyme removes the phosphate on carbon #1 of fructose 1,6-­bisphosphate to produce fructose 6-phosphate

Answer 38

FBP-1

Question 39

Are an enzyme pair for glycolysis/gluconeogenesis in the same way that glycogen synthase and phosphorylase are for glycogen metabolism

Answer 39

PFK-1 and FBP-1

Question 40

Allosteric regulation of fructose 1,6-­bisphosphatase is effected by

Answer 40

AMP and Fructose 2,6-bisphosphate

Question 41

Serves as a local signal of energy need

Answer 41

AMP

Question 42

Gluconeogenesis is an energy requiring process, so AMP inhibits the

Answer 42

FBP-1

Question 43

Fructose 2,6-­bisphosphate allosterically inhibits

Answer 43

FBP-1

Question 44

The principal regulatory site in the glycolysis/gluconeogenesis story

Answer 44

PFK-1/FBP-1

Question 45

Remember that insulin and glucagon also regulate

Answer 45

Pyruvate kinase

Question 46

Glucagon-­mediated phosphorylation of this enzyme prevents the conversion of -conserves it for gluconeogenesis

Answer 46

PEP

Question 47

The final step in gluconeogenesis is the conversion of glucose 6-phosphate to free glucose, but we are unable to use the ATP-­consuming enzyme

Answer 47

Glucokinase

Question 48

Instead, a membrane-­bound complex of proteins catalyzes this step. This complex of proteins includes the enzyme

Answer 48

Glucose-6-phosphatase

Question 49

This reaction takes place in the

Answer 49

ER

Question 50

Glucose 6-­phosphate is transported into the ER, where it reacts with the membrane-­bound

Answer 50

Phosphatase

Question 51

Genetic deficiency for glucose 6-­phosphatase in liver has been characterized extensively and is referred to as

Answer 51

Von Gierke’s Disease, also called Type 1 Glycogen Storage Disease)

Question 52

Gluconeogenesis is an energy consuming process. In order to convert lactate to glucose, the liver (and kidney) must consume the equivalent of

Answer 52

6 ATPs (4 ATP and 2 GTP)

Question 53

While ATP has no direct allosteric effect on gluconeogenic enzymes, it inhibits two

Answer 53

Rate-limiting glycolytic enzymes

Question 54

In this way, high levels of ATP help to stimulate net

Answer 54

Gluconeogenesis

Question 55

In this way, high levels of ATP help to stimulate net gluconeogenesis by ensuring the inhibition of the counter directional enzymes

Answer 55

Pyruvate kinase and PFK-1

Question 56

An intermediate of the TCA cycle that inhibits PFK-1

Answer 56

Citrate

Question 57

It is principally at the fructose 6-­phosphate/fructose 1,6-bisphosphate stage of things that we see control via

Answer 57

Glucagon and insulin

Question 58

Liver interprets high insulin/glucagon ratios as a sign of carbohydrate energy abundance, and inhibits

Answer 58

Gluconeogenesis

Question 59

Conversely, it treats low insulin/glucagon ratios as a signal of carbohydrate energy deficiency, and therefore throttles up

Answer 59

Gluconeogenesis

Question 60

Functions to clear the lactate that is produced by anaerobic glycolysis

Answer 60

The Cori Cycle

Question 61

Has one end point and many potential start points

Answer 61

Gluconeogenesis

Question 62

Eighteen of the twenty common amino acids are able to donate their carbon skeletons to

Answer 62

Gluconeogenesis

Question 63

Integral to this is the disposal of the amine nitrogen on amino acids, tightly linking gluconeogenesis via amino acids to the process of

Answer 63

Urea Production (I.e. The Urea Cycle)

Question 64

The use of substantial quantities of amino acids for gluconeogenesis is reserved, in large part, to the circumstance of an

Answer 64

Extended fast

Question 65

What are the only two amino acids that are unable to participate in gluconeogenesis?

Answer 65

Leucine and Lysine

Question 66

Leucine and lysine are "ketogenic", meaning their catabolism leads only to

Answer 66

Acetyl CoA

Question 67

Similarly, fatty acids composed of an even number of carbons produce only - Via the process of B-oxidation - Cannot participate in gluconeogenesis

Answer 67

Acetyl CoA

Question 68

Not a tenable source of carbon atoms for gluconeogenesis

Answer 68

Acetyl CoA

Question 69

Acetyl CoA and OAA combine to produce

Answer 69

Citrate

Question 70

Acetyl CoA doesn’t contribute net carbon atoms to the ensemble of -Thus why it can not contribute to gluconeogenesis

Answer 70

TCA cycle intermediates

Question 71

Contrasting this, those 18 glucogenic amino acids are able to contribute to the pools of TCA cycle intermediates without consuming a TCA cycle intermediate. Such a contribution is referred to as an

Answer 71

Anapleurotic reaction

Question 72

When there is net production of a TCA cycle intermediate, there is no problem in feeding OAA into

Answer 72

Gluconeogenesis

Question 73

Free glycerol, produced when the three fatty acids of a TAG are released, is taken up by the liver and in two reactions, catalyzed by

Answer 73

Glycerol Kinase and Glycerol-3-phosphate dehydrogenase

Question 74

In this process, glycerol is converted into

Answer 74

Dihydroxyacetone phosphate

Question 75

Has a number of metabolic sources, including catabolism of valine and isoleucine, and the conversion of cholesterol to bile salts

Answer 75

Propionate

Question 76

Also derives from fatty acids with branch structures and from fatty acids with an odd number of carbons

Answer 76

Propionate

Question 77

Following a carboxylation reaction, propionate donates its carbons to the synthesis of -another example of an anapleurotic reaction

Answer 77

Succinyl CoA

Question 78

The neonate’s liver glycogen stores are typically

Answer 78

Modest

Question 79

Its ability to metabolize certain types of fatty acids for energy is also markedly reduced, compared to even slightly older babies

Answer 79

Neonates

Question 80

Also, the neonate’s brain to body ratio is the largest it will ever be and hence the brain places a disproportionate demand on the child’s

Answer 80

Glucose supply

Question 81

The matter is compounded by the fact that in the newborn, a critical liver enzyme in gluconeogenesis is in very low levels. This enzyme is

Answer 81

PEP carboxykinase (PEPCK)

Question 82

As limited glycogen stores are depleted in the first few hours after birth, gluconeogenesis must step in to fill the gap. In the absence of adequate levels of PEP carboxykinase, we may see

Answer 82

Hypoglycemia