Gluconeogenesis

Question 1

tissues that depend mainly on glucose
circumstances of gluconeogenesis

Answer 1

brain, RBC, testes, renal medulla, embryo

during vigorous exercise and following, fasting, between meals

Question 2

main location of gluconeogenesis

Answer 2

liver, renal cortex, intestinal epithelium

Question 3

gluconeogenesis in plants vs animals

Answer 3

plants: CO2 fixation –> 3-phosphoglycerate, which can be converted to glucose-6-phosphate

animals: lactate converted to pyruvate which can be converted to phosphoenolpyruvate and then glucose -6-phosphate
also glycerol can be converted to glucose-6-phosphate

Question 4

energy requirements for gluconeogenesis

Answer 4

1 glucose requires 6 ATP (4 ATP + 2 GTP) and 2 NADH

2 ATP per glucose
1. Pyruvate carboxylase: Pyruvate + HCO3 –> oxaloacetate
2. Phosphoglycerate kinase: 3-phosphoglycerate –> 1,6-bisphosphoglycerate

2 NADH per glucose:
Glyceraldehyde-3-phosphate dehydrogenase complex: 1,3-bisphosphoglycerate –> G3P

2 GTP per glucose
1. PEP carboxykinase: Oxaloacetate –> malate

Question 5

Key reactions in gluconeogenesis

Answer 5

1, 3, and 10 of glycolysis (so 1, 7 and 10 in gluconeogenesis)
the irreversibles
require different enzymes from glycolysis

Question 6

Step 1 gluconeogenesis

Answer 6

Part 1: Bicarbonate + Pyruvate –> oxaloacetate
Enzyme: pyruvate decarboxylase
Cofactors: ATP, biotin
location: mitochondria

Part 2: Oxaloacetate –> Malate
Enzyme: malate dehydrogenase
Cofactors: GTP
Location: mitochondria (oxaloacetate cannot leave mitochondria)

Part 3: Malate –> phosphoenolpyruvate + CO2
Enzyme: PEP carboxykinase
Location: cytosol or mitochondria

Reversibility: Irreversible

Question 7

Step 7 Gluconeogenesis

Answer 7

Fructose 1,6-bisphosphate –> Fructose 6-phosphate
Enzyme: fructose 1,6-bisphosphatase-1
Cofactor: H2O
Reversibility: irreversible

Question 8

Step 10 Gluconeogenesis

Answer 8

Glucose-6-phosphate –> glucose
Enzyme: glucose-6-phosphatase
Cofactor: H2O
Reversibility: irreversible

Question 9

ketogenic amino acids

Answer 9

leucine and lysine

Question 10

pentose phosphate pathway more common in

Answer 10

alternative fate of glucose-6-phosphate
highly proliferative cells, cells that do fatty acid and sterol synthesis, cells with high oxidative stress

Question 11

products of pentose phosphate pathway

Answer 11

ribose-5-phosphate and NADPH
no ATP produced or consumed

Question 12

Step 1 Pentose Phosphate Pathway

Answer 12

Part 1: Glucose-6-phosphate –> 6-phosphogluconate + NADPH
Enzyme: G6P dehydrogenase
Cofactors: NADP+

Part 2: 6-phosphogluconate –> Ribulose 5-phosphate + NADPH + CO2
Enzyme: 6-phosphogluconate dehydrogenase
Cofactors: NADP+

Question 13

Step 2 Pentose Phosphate Pathway
product can go on to

Answer 13

Ribulose 5-phosphate –> Ribose-5-phosphate
Enzyme: phospho-pentose isomerase
Cofactors: none

Can go on to produce nucleotides, coenzymes, DNA, RNA

Question 14

NADPH from Pentose Phosphate Pathway

Answer 14

in high oxidation tissues (cornea and RBC):
GSSG (oxidized glutathione) –> GSH (reduced glutathione)
Enzyme: glutathione reductase
Cofactor: NADPH

in fatty acid synthesis tissues (liver, adipose, mammary glands):
Precursors –> fatty acids, sterols
Enzyme: fatty acid synthase
Cofactor: NADPH

NADPH does not go on to produce ATP, just acts as a reducing agent

Question 15

Glutathione oxidative damage prevention pathway

Answer 15

•O2- (superoxide radical) + 2H+ –> hydrogen peroxide (H2O2)
•OH from H2O2 creates oxidative damage to lipids, proteins and DNA

2 GSH + H2O2 –> 2H2O + GSSG
prevents oxidation reaction

Question 16

Glutathione oxidative damage prevention pathway

Answer 16

O2- (superoxide radical) + 2H+ –> hydrogen peroxide (H2O2)
OH from H2O2 creates oxidative damage to lipids, proteins and DNA

2 GSH + H2O2 –> 2 H2O + GSSG
Enzyme: glutathione peroxidase
prevents oxidation reaction

Question 17

Recycling of glutathione

Answer 17

GSSG + NADPH + H+ –> NADP+
Enzyme: glutathione reductase

G6P + NADP+ –> Ribulose-5-phosphate + NADPH
Enzyme: glucose-6-phosphate dehydrogenase

Question 18

sources of oxidative damage

Answer 18

mitochondrial respiration, ionizing radiation, sulfa drugs, herbicides, antimalarials, divicine, deficiency of glucose-6-phosphate dehydrogenase (causes hemolytic anemia)

Question 19

Non-oxidative Phase Pentose Phosphate Pathway Function

Answer 19

Occurs in tissues requiring more NADPH than R-5-P
Goal: to regenerate glucose-6-phosphate from ribose-5-phosphate oxidative pathway
Converts 6 5-Carbon molecules into 5 6-Carbon molecules
For when the cell doesn’t need R-5-P, but needs NADPH

Question 20

Non-oxidative Phase Pentose Phosphate Pathway

Answer 20

1) Ribulose-5-phosphate –> xylulose-5-phosphate
Enzyme: epimerase
or
Ribulose-5-phosphate –> ribose-5-phosphate
Enzyme: isomerase

2) Ribose-5-phosphate + xylulose-5-phosphate –> sedoheptose-7-phosphate + glyceraldehyde-3-phosphate
Enzyme: transketolase

3) sedoheptose-7-phosphate + glyceraldehyde-3-phosphate –> fructose-6-phosphate + erythrose-4-phosphate
Enzyme: transaldolase

3) fructose-6-phosphate –> glucose-6-phosphate
AND erythrose-4-phosphate + xylulose-5-phosphate –> fructose-6-phosphate + glyceraldehyde-3-phosphate (TCA)
Enzyme: transketolase

4) fructose-6-phosphate –> glucose-6-phosphate

2x glucose-6-phosphate produce via the 2 branching pathways
intermediates from different pathways overlap

Question 21

regulation of pentose phosphate pathway

Answer 21

negative feedback of NADPH inhibits glycogen-6-phosphate dehydrogenase
- high NADP+ stimulates pentose phosphate pathway
- non-oxidative pathway increases with NADPH needs

G6P partitioning depending on cell needs