Gluconeogenesis and Pentose Phosphate Pathway Flashcards

Flashcards for reviewing gluconeogenesis and pentose phosphate pathway.

What is Gluconeogenesis?

Synthesis of glucose from non-carbohydrate precursors.

When are glucose stores depleted?

Periods of starvation or fasting beyond a day.

How much glucose does the brain rely on as a source of energy?

120g/d

Since the brain relies on glucose as a source of energy, where must glucose be synthesized from?

Molecules other than carbohydrates.

What molecule can be converted to glucose?

Pyruvate

What are some examples of glucogenic molecules?

Lactate and several amino acids.

Besides lactate and amino acids, what is another glucogenic molecule?

Glycerol

What color are the enzymes that belong to the gluconeogenic pathway shown in the lecture slides?

Red

What do the enzymes in the gluconeogenic pathway do?

They overcome the high negative free energy of the irreversible reactions of glycolysis.

What color are the enzymes held in common between the glycolytic & gluconeogenic pathways in the lecture slides?

Blue

Name the irreversible glycolytic enzymes.

Hexokinase, Phosphofructokinase, Pyruvate kinase

What is the ΔG of Hexokinase?

ΔG = -8 kcal mol-1

What is the ΔG of Phosphofructokinase?

ΔG = -5.3 kcal mol-1

What is the ΔG of Pyruvate kinase?

ΔG = -4.0 kcal mol-1

Name the enzymes of gluconeogenesis.

Pyruvate carboxylase, Phosphoenolpyruvate carboxykinase , Fructose 1,6-bisphosphatase, Glucose 6-phosphatase

What is used as a cofactor in Pyruvate Carboxylase?

Biotin

What is Pyruvate carboxylase allosterically activated by?

Acetyl-CoA

What does the presence of Acetyl-CoA in Pyruvate Carboxylase indicate about the cell?

Low energy state

What is the metabolic role of Pyruvate Carboxylase?

Anaplerotic for the TCA cycle – replenishes OAA

Where does Pyruvate carboxylase take place?

Mitochondria

When does the synthesis of PEPCK increase?

Fasting

Where does Phosphoenolpyruvate carboxykinase (PEPCK) take place?

Cytosol

Where is Pyruvate carboxylated?

Mitochondria

What is oxaloacetate converted to in order to pass out of the mitochondria?

Malate

Where is oxaloacetate converted back in the gluconeogenesis pathway?

Cytosol

What type of reaction is Fructose 1,6-bisphosphatase?

A metabolically irreversible reaction

What is F1,6BPase allosterically inhibited by?

AMP and fructose 2,6-bisphosphate (F2,6BP)

What type of reaction is Glucose 6-phosphatase?

Metabolically irreversible hydrolysis reaction

Where is Glucose-6-phosphatase found?

Liver and kidney

What is Glucose 6-P a precursor for?

Glycogen synthesis and Glucose synthesis

What tissues is glucose 6-phosphatase present in?

Liver and kidney

Where is glucose 6-phosphatase highly regulated?

Liver

What are the products of Gluconeogenesis Stoichiometry?

glucose + 4ADP + 2GDP +6Pi +2NAD+ + 2H+; G°’ = -9kcal mol-1

What are the reactants of Gluconeogenesis Stoichiometry?

2pyruvate + 4ATP + 2GTP + 2NADH + 6H2O

What is the reverse of Gluconeogenesis?

Glycolysis

What is the G°’ of Glycolysis?

20kcal mol-1

How many nucleotide triphosphate molecules does it take to synthesize glucose?

6

How many nucleotide triphosphate molecules are generated from glycolysis?

2

How many extra high phosphoryl-transfer potential molecules does it take to drive the unfavorable gluconeogenesis pathway?

Four

What through a pathway is controlled at rate- limiting steps?

Flux

What are some mechanisms that may alter flux through the rate-determining, exergonic steps?

Allosteric control, Covalent modifications, Substrate cycles, Genetic control

A high [AMP] indicates that the energy charge is what and signals the need for ATP?

Low

High [ATP] and [citrate] indicate the energy charge is what and intermediates are abundant?

High

What stimulates gluconeogenesis?

Glucagon

What stimulates glycolysis?

Insulin

What substrate cycles are regulated by Glucagon & Glycolysis?

PFK-1 & FBPase-1

What does Glucagon inhibit?

Glycolysis

What does Insulin inhibit?

Gluconeogenesis

What regulates PFK-1 & FBPase-1?

Fructose 2,6-P2

Does Fructose 2,6-P2 inhibits or activate FBPase-1?

Inhibits

Does Fructose 2,6-P2 inhibits or activate PFK-1?

Activates

Carl and Gerty Cori won the Nobel Prize in Physiology and medicine 1947 “for their discovery of the course of the catalytic conversion of what?

Glycogen

What is the Cori Cycle?

The interaction of glycolysis and gluconeogenesis

In the Cori Cycle, where does the Lactate from peripheral tissues go?

Liver

What does the Liver use for energy in the Cori Cycle?

Lipid

What placement does the Liver have in the Circulation?

First pass at removing nutrients absorbed from the intestine

What types of metabolic fuels does the liver participate in interconversions of?

Carbohydrates, amino acids, fatty acids

What regulates distribution of dietary fuels and supplies fuel from its own reserves?

The liver

What is another name for Hexose phosphate Shunt?

Pentose Phosphate Pathway

What are the important products of pentose phosphate pathway?

NADPH and ribose 5-phosphate

What type of biosynthesis is NADPH used for?

Reductive biosynthesis

What is NADPH also important in?

Elimination of oxygen radicals

What is ribose 5-phosphate used for?

Ribonucleotides

In what tissues is the Pentose Phosphate Pathway highly active?

Mammary glands, liver, adrenal glands, adipose

In what tissues is the Pentose Phosphate Pathway not active?

Brain and muscle

Where are the enzymes of Pentose Phosphate Pathway located?

Cytosolic

What are the two stages of Pentose Phosphate Pathway?

Oxidative stage and Non-oxidative stage

What happens during the Oxidative Phase in Pentose Phosphate Pathway?

Production of 2 NADPH and ribulose-5-phosphate from glucose-6-phosphate

What happens during the Nonoxidative Phase in Pentose Phosphate Pathway?

Disposes excess pentose phosphates by converting to glycolytic intermediates

What kind of reactions happen in the Nonoxidative Phase in Pentose Phosphate Pathway?

C-C bond cleavage and formation reactions

What is the first reaction in the Nonoxidative Phase in Pentose Phosphate Pathway?

Ribulose 5-P à Ribose 5-P or Xylulose 5-P

What is the second reaction in the Nonoxidative Phase in Pentose Phosphate Pathway?

2 Xylulose 5-P + Ribose 5-P à 2 Fructose 6-P + GAP

What enzymes have broad substrate specificities in the Nonoxidative Phase in Pentose Phosphate Pathway?

Transketolase and transaldolase

What do Transketolase and transaldolase catalyze in the Nonoxidative Phase in Pentose Phosphate Pathway?

They catalyze the exchange of two- and three-carbon fragments between sugar phosphates

What is the substrate for Transketolase and transaldolase enzymes in the Nonoxidative Phase in Pentose Phosphate Pathway?

One substrate is an aldose, one substrate is a ketose

In what tissues does FA synthesis by NADPH occur?

liver, adipose, mammary

In what tissues does Cholesterol synthesis by NADPH occur?

liver

In what tissues does Steroid hormone synthesis by NADPH occur?

adrenal, ovaries, testes

In what tissues does Detoxification (Cytochrome P-450 System) by NADPH occur?

liver

In what tissues does Reduced glutathione as an antioxidant by NADPH occur?

RBC

In what tissues does Generation of superoxide radicals: microbicidal activity by NADPH occur?

neutrophils

Where does Regulation of Pentose Phosphate Pathway occur?

occurs with Glucose 6-P Dehydrogenase

What is the First step – Rate limiting enzyme in Pentose Phosphate Pathway?

Glucose 6-P dehydrogenase

How is Glucose 6-P dehydrogenase allosterically regulated?

Feedback inhibited by NADPH

What induces Glucose 6-P dehydrogenase?

Insulin

What is the Production of superoxide reaction in the Role of NADPH in Red Blood Cells?

Hb-Fe2+-O2 -> Hb-Fe3+ + O2-

What is the second step reaction in the Role of NADPH in Red Blood Cells?

O2- . + 2H2O -> 2H2O2

What do O2- . & H2O2 do?

Damage cell membranes, and cause hemolysis

What are the antioxidant enzymes?

Superoxide dismutase, Glutathione peroxidase, Glutathione reductase

What are the sources of glucose that support life that are mentioned?

Absorptive phase, Postabsorptive phase, Early starvation, Intermediate starvation, Prolonged starvation

What are the Glucose uses in grams per hour?

Exogenous, Glycogen, Gluconeogenesis

How much glucose is used in the absorptive phase?

40 grams per hour

What glucose source is used in the absorptive phase?

Exogenous

How much glucose is used in the postabsorptive phase?

30 grams per hour

What glucose source is used in the postabsorptive phase?

Glycogen

How much glucose is used in the early starvation phase?

20 grams per hour

What glucose source is used in the early starvation phase?

Gluconeogenesis

What is the time measurement for the first half of the graph?

Hours

What is the time measurement for the second half of the graph?

Days

What molecules use hexokinase?

ATP