Gluconeogenesis

Question 1

Uses non-carbohydrates to produce glucose:

Answer 1

Lactate
Amino acids
Glycerol
Proprionyl CoA from Odd chain fatty acids

Question 2

Gluconeogenesis occurs in

Answer 2

Liver 90%

Kidneys 10% major glucose producing organ in prolonged starvation

Question 3

This pathway is important for

Answer 3

maintaining normal blood glucose levels

Question 4

First step in gluconeogenesis is conversion of

by the enzyme

Happens in

Answer 4

Pyruvate -> oxaloacetate

Pyruvate carboxylase

Mitochondria of liver and kidney only kasi walang pyruvate carb sa muscle

Question 5

Conversion of pyruvate from cytosol to oxaloacetate by pyruvate decarboxylase occurs in

Answer 5

mitochondria of liver and kidney

Question 6

Pyruvate carboxylase in the mitochondria requires the coenzyme

Answer 6

Biotin B7

bound to lysine forming active biocytin

Question 7

Pyruvate carboxylase is stimulated or regulated or allosterically regulated by

Answer 7

Inc levels of Acetyl CoA

Ex starvation and to replenish TCA
Inactive at low levels of acetyl coa and pyruvate is oxidized instead in TCA

Question 8

During fasting, there is increased Acetyl Coa because fat is metabolized for energy

Answer 8

Fatty acids are metabolized by liver by beta oxidation with end product of Acetyl CoA

Question 9

During starving, gluconeogenic amino acids and proprionyl coA (odd-chain fatty acids) can be shuttled to TCA to produce ATP

Answer 9

Inc ATP inhibits Kreb’s cycle and beta oxidation causing acetyl coA to rise hence activating pyruvate carboxylase

Question 10

An experiment is performed on mice with knockout mutation resulting in inability to metabolize triglycerides.

After several days without food, how will the activity of the enzymes pyruvate carboxylase and glycerol kinase likely be altered in the knockout mice compared to healthy mice?

Answer 10

Decreased TAG metabolism leads to decreased fatty acid oxidation decreasing acetyl coA and decreasing pyruvate carboxyalse leading to decreased gluconeogenesis

Decreased TAG metabolism leads to dec glycerol leading to dec glycerol kinase

Question 11

Decreased glycerol leads to a decrease in

Answer 11

DHAP with decreased activity Glycerol kinase

Question 12

Second step:

Oxaloacetate from mitochondria is converted into this substrate to enter the cytosol

Answer 12

Malate by enzyme malate dehydrogenase

Question 13

Oxaloacetate should be converted into Malate because in order for it to be shuttled to

Answer 13

cytosol because it cannot cross the mitochondrial membrane

Malate shuttle

Question 14

NADH is generated each time malate is converted into oxaloacetate and is shunted by

Answer 14

Malate shuttle

Question 15

Once in the cytoplasm, malate is convered back to

Answer 15

Oxaloacetate also generating

NADH

Question 16

Third step: In the cytosol, oxaloacetate is converted to or decarboxylated and phosphorylated

by the enzyme

Answer 16

Phosphoenolpyruvate

Phosphoenolpyruvate carbokinase (PEPCK) 
pyruvate carboxylase

using up GTP to become GDP

Provides energetically favorable pathway from pyruvate to PEP

Question 17

GTP utilized by PEPCK to convert Oxaloacetate to phosphoenolpyruvate comes from this reaction of TCA

Answer 17

Succinyl coa -> succinate by succinate synthase

Question 18

Step 4: Phosphoenolpyruvate is converted to

By enzyme

Answer 18

Fructose 1,6 bisphosphate

Fructose 1,6 bisphosphatase bypasses the irreversible PFK1

*regulatory site of gluconeogenesis

Question 19

Increase in fructose 1,6 bisphosphate allows conversion to frucose 6 phosphate. Fructose 6 phosphate is converted to glucose 6 phosphate.

Glucose 6 phosphate is converted to glucose by the enzyme

Answer 19

Glucose 6 phosphatase

Question 20

Glucose 6 phosphate is converted to glucose in the

Answer 20

Liver and kidneys

Question 21

This upregulates or increases activity of glucose 6 phosphatase

Answer 21

Glucagon

Question 22

Deficiency of glucose 6 phosphatase is

Answer 22

Von Gierke’s

Type I GSD

Question 23

Lactate
Gluconeogenic amino acids

enter gluconeogenesis via

Answer 23

Pyruvate in cytosol

Question 24

Glycerol enters gluconeogenesis via

Answer 24

DHAP in cytoplasm

Question 25

``` Gluconeogenic amino acids Proprionyl CoA (from odd-chain fatty acids) enter gluconeogenesis via ```

Answer 25

TCA in matrix of mitochondria

Question 26

17/M 2 month history of weight loss, depression and a red blistering rash primarily affecting the leg Two days ago, developed DVT Rash consistent with necrolytic migratory erythema Hyperglycemia How will activity of fructose 1,6 bisphosphate and glucose 6 phosphatase likely be altered?

Answer 26

Glucagonoma (Dermatitis, Depression, Declining weight, DVTs) Glucagon dec concentration of fructose 2,6 bisphosphate by increasing activity of fructose 2,6 bisphosphate fructose 1,6 bisphosphatase activity is increased resulting in increased conversion of fructose 6 phosphate and increases glucose 6 phosphatase hence increased gluconeogenesis

Question 27

Liver glycogen can only sustain glucose in absence of carbohydrate intake within

Answer 27

10-18 hours

Question 28

4 alternate reactions that energetically favor synthesis of glucose

Answer 28

(Carboxylation of pyruvate) pyruvate -> oxaloacetate (Transport of oxaloacetate to cytosol) Oxaloacetate -> phosphoenolpyruvate (Decarboxylation of cytosolic oxaloacetate) (Dephosphorylation of fructose 1,6 bisphosphate) Fructose 1,6 -> fructose 6 Glucose 6 phosphate -> glucose

Question 29

Fructose 1,6 bisphosphatase is inhibited by

Answer 29

inc AMP signalling poor energy state | Fructose 2,6 bisphosphatase (allosteric) influenced by glucagon

Question 30

Fructose 1,6 bisphosphatase is stimulated by

Answer 30

ATP Low AMP stimulating gluconeogenesis

Question 31

Final step in gluconeogenesis

Answer 31

Glucose 6 phosphatase -> glucose by glucose 6 phosphatase

Question 32

Deficiency of enzyme on the last step of gluconeogenesis leads to

Answer 32

Von Gierke Type 1 Glucose 6 Phosphatase deficiency

Question 33

``` Affects liver, kidney and intestine Fasting hypoglycemia severe Fatty liver and hepatomegaly Hyperlactiacidemia and hyperuricemia Normal glycogen structure increased glycogen stored ```

Answer 33

Von Gierke’s Glucose 6 Phosphatase Deficiency | Type I

Question 34

Most important GLUCONEOGENIC precursors

Answer 34

Glycerol - from hydroysis of TAG Lactate - from RBC and skeletal muscle ; from Cori cycle (blood glucose -> lactate by muscle) Ketoacids (pyruvate, oxaloacetate and alpha-ketoglutarate) from glycogenic amino acids forming oxaloacetate

Question 35

Alpha keto acids from metabolism of glycogenic amino acids

Answer 35

Pyruvate Oxaloacetate a-ketoglutarate

Question 36

Ketogenic compounds like acetyl coa from acetoacetate and ketogenic amino acids cannot give rise to synthesis of glucose because

Answer 36

Pyruvate to Acetyl coa by Pyruvate dehydrogenase is irreversible Instead they give rise to ketone bodies

Question 37

Hormone stimulating gluconeogenesis by 1) allosteric effect (low fructose 2,6 inc fructose 1,6 bisphosphatase and inhibition of PFK)? 2) covalent modification (inc cAMP and cAMP Protein kinase stimulates pyruvate kinase to inactive phosphorylated form) dec PEP to pyruvate

Answer 37

Glucagon

Question 38

Gluconeogenesis is regulated by

Answer 38

Glucagon Substrate availability (glycerol, lactate, a-ketoacids) Mobilization of amino acids from muscle protein and provide carbon skeletons for gluconeogenesis Allosteric activation of pyruvate carboxylase by acetyl coa accumulation

Question 39

Glucogenic Amino acids

Answer 39

``` Glycine Serine Valine Histidine Arginine Cysteine Proline Alanine Glutamate Glutamine Aspartate Asparagine Methionine ```

Question 40

Both glucogenic and ketogenic amino acids

Answer 40

Tryptophan Tyrosine Isoleucine Phenylalanine

Question 41

Ketogenic amino acids

Answer 41

Leucine | Lysine

Question 42

Glycogen reserves drop after

Answer 42

12 hours Inc gluconeogenesis After 24 h, gluconeogesis is sole source

Question 43

Between meals, what happens to fatty acids

Answer 43

oxidation of fatty acids in liver -> acetyl coa accumulates -> pyruvate carboxylase converts pyruvate to oxaloacetate and conversion of lactate and alanine to acetyl coa prevented

Question 44

In the well fed state, what happens to acetyl coa

Answer 44

Acetyl coa accumulated is shuttled to cytoplasm for fatty acid synthesis from increased pyruvate formation (pyruvate dehydrogenase)

Question 45

Alcoholics are susceptible to hypoglycemia because of

Answer 45

the formation of high amounts of cytoplasmic NADH from alcohol dehydrogenase and acetaldehyde dehydrogenase

Question 46

Key central point of gluconeogenesis | Activated by ATP

Answer 46

Fructose 1,6 bisphosphate

Question 47

Fructose 1,6 bisphosphate is inhibited by

Answer 47

AMP | Fructose 2,6 bisphosphate

Question 48

Present in lumen of ER of liver Glucose 6P is transported into ER and free glucose is transported back into cytoplasm Absent in skeletal muscle accounting for the the fact that muscle glycogen cannot serve as source of blood glucose

Answer 48

Glucose-6 phosphatase