Glycolysis, Gluconeogenesis, and the Pentose Phosphate Pathway

6-Phosphogluconate
(Pentose Phosphate Pathway Oxidative Phase)

Undergoes oxidation and decarboxylation by the enzyme 6-Phosphogluconate dehydrogenase to for the ketopentose RIBULOSE 5-PHOSPHATE
This reaction generates a second molecule of NADPH

Ribulose 5-Phosphate
(Pentose Phosphate Pathway Oxidative Phase)

The enzyme Phosphopentose isomerase converts Ribulose 5-Phosphate to its aldose isomer, RIBOSE 5-PHOSPHATE

Glucose 6 Phosphate
(Pentose Phosphate Pathway Oxidative Phase)

G6P is oxidized by the enzyme Glucose 6 Phospate Dehydrogenase (G6PD) to form 6-PHOSPHOGLUCONO-BETA-LACTONE.
NADP+ is the electron acceptor and forms NADPH

6-Phosphoglucono-Beta-Lactone
(Pentose Phosphate Pathway Oxidative Phase)

The lactone is hydrolyzed to the free acid 6-PHOSPHOGLUCONATE by a specific enzyme Lactonase

1 molecule of glucose

Formation of one molecule of glucose from pyruvate requires 4 ATP, 2 GTP, and 2 NADH; it is expensive

1,3 Bisphosphoglycerate

The enzyme PHOSPHOCLYCERATE KINASE transfers the high-energy phosphoryl group from the carboxyl group of 1,3 phosphoglycerate to ADP, forming ATP and 3-PHOSPHOGLYCERATE

2-Phosphoglycerate

In the 2nd glycolytic reaction that generates a compound with high phosphoryl group transfer potential , ENOLASE promotes reversible removal of a molecule of water from 2-phosphoglycerate to yield PHOSPHOENOLPYRUVATE (PEP)

3-Phosphoglycerate

The enzyme PHOSPHOGLYCERATE MUTASE catalyzes a reversible shift of the phosphoryl group beween C-2 and C-3 of glycerate; Mg2+ is essential for this reaction. 2-PHOSPHOGLYCERATE

Acyl Phosphate

Any molecule with the general chemical form R-C
=O-O-(OPO3)2-

Anaerobic / Hypoxic Conditions

Many organisms regenerate NAD+ by transferring electrons from NADH to pyruvate, forming lactate.

Animals

Cannot convert acetyl-CoA derived from fatty acids into glucose; plants and microorganisms can

Biotin

A vitamin; an enzyme cofactor involved in carboxylation reactions

Briefly describe the possible metabolic fates of pyruvate produced by glycolysis in humans, and explain the circumstances that favor each

Under aerobic conditions, pyruvate is oxidized to acetyl-CoA and passes through the citric acid cycle. Under anaerobic conditions, pyruvate is reduced to lactate to recycle NADH to NAD+, allowing the continuation of glycolysis

Dihydroxyacetone Phosphate

Dihydroxyacetone Phosphate, is rapidly and reversibly converted to GLYCERALDEHYDE 3 PHOSPHATE by the enzyme TRIOSE PHOSPHATE ISOMERASE

Ethanol (Alcohol) Fermentation

The anaerobic conversion of glucose to ethanol via glycolysis; also called alcohol fermentation.

Ethanol Fermentation

1st - Pyruvate is decarboxylated in an irreversible reaction catalyzed by the enzyme pyruvate decarboxylase; does not involve the net oxidation of pyruvate. Requires Mg2+ and has a tightly bound coenzyme, thiamine pyrophosphate
2nd - Acetaldehyde is reduc

Explain why Pi is absolutely required for glycolysis to proceed

Inorganic Phosphate is an essential substrate in the reaction catalyzed by glyceraldehyde 3-phosphate dehydrogenase

Fermentation

Energy-yielding anaerobic breakdown of a nutrient molecule, such as glucose, without net oxidation; yields lactate, ethanol, or some other simple product.

Fructose 1,6 Bisphosphate

The enzyme ALDOLASE catalyzes a reversible aldol condensation. Fructose 1,6 Bisphosphate is cleaved to yield two different triose phosphates, GLYCERALDEHYDE 3 PHOSPHATE, an aldose, and DIHYDROXYACETONE PHOSPHATE, a ketose

Fructose 1,6-bisphosphate>>>F6P

This reaction is highly exergonic and irreversible. The generation of F6P from FRUCTOSE 1,6-BISPHOSPHATE is catalyzed by the Mg2+-dependent enzyme FRUCTOSE 1,6-BISPHOSPHATASE

Fructose 6 Phosphate

PHOSPHOFRUCTOKINASE-1 catalyzes the transfer of a phosphoryl group from ATP to F6P to yield FRUCTOSE 1,6 BISPHOSPHATE

G6P>>>>Glucose

Reversal of the hexokinase reaction would require phosphoryl group transfer from G6P>ADP, forming ATP, an energetically unfavorable reaction. This reaction is catalyzed by the enzyme GLUCOSE 6-PHOSPHATASE

Glucogenic

Amino acids derived from proteins are ultimately catabolized to pyruvate and can therefore undergo net conversion to glucose - alanine, cysteine, glycine, serine, threonine, and tryptophan

Gluconeogenesis

The biosynthesis of a carbohydrate from simpler, noncarbohydrate precursors such as oxaloacetate or pyruvate

Glucose

Irreversible under intracellular conditions; glucose is activated by the enzyme HEXOKINASE to be phosphorylated at C-6 to yield GLUCOSE 6 PHOSPHATE

Glucose 6 Phosphate

The enzyme PHOSPHOHEXOSE ISOMERASE catalyzes the reversible isomerization of glucose 6 phosphate, an aldose, to FRUCTOSE 6 PHOSPHATE, a ketose

Glyceraldehyde 3 Phosphate

Oxidation of Glyceraldehyde 3 Phosphate is catalyzed by the enzyme GLYCERALDEHYDE 3 PHOSPHATE DEHYDROGENASE to produce 1,3 BISPHOSPHOGLYCERATE
This is the first of the two energy conserving reactions of glycolysis that eventually lead to the formation of

Glycogen

Converted to monosaccharide units by the enzyme GLYCOGEN PHOSPHORYLASE

Glycolysis

The catabolic pathway by which a molecule of glucose is broken down into two molecules of pyruvate

Hexose Monophosphate Pathway /
Pentose Phosphate Pathway

A pathway present in most organisms that serves to interconvert hexoses and pentoses and is a source of reducing equivalents (NADPH) and pentoses for biosynthetic processes

Hypoxia

The metabolic condition in which the supply of oxygen is severely limited

In mammals

Gluconeogenesis in the liver, kidney, and small intstine provides glucose for use by the brain, muscles, and erythrocytes

In the conversion of glucose to pyruvate via glycolysis, all of the following enzymes participate. Indicate the order in which they function by numbering them

Hexokinase, Phosphohexose isomerase, Phosphofructokinase-1, Triose Phosphate Isomerase, Glyceraldehyde 3-phosphate Dehydrogenase, Enolase, Pyruvate Kinase

Isomerases

Enzymes that catalyze the transformation of compounds into their positional isomers

Isozymes

Multiple forms of an enzyme that catalyze the same reaction but differ in amino acid sequence, substrate affinity, V max, and/or regulatory properties; also called isoenzymes

Mutases

Enzymes that catalyze the transposition of functional groups

NADH

Formed in glycolysis must be recycled to regenerate NAD+, which is required as an electron acceptor in the first step of the payoff phase. Under aerobic conditions, electrons pass from NADH to O2 in mitochondrial respiration

Phosphoenolpyruvate

The last step in glycolysis is the transfer of the phosphoryl group from phosphoenolpyruvate to ADP, catalyzed by the enzyme PYRUVATE KINASE, which requires K+ and either Mg2+ or Mn2+. Produces Pyruvate and ATP

Pyruvate Carboxylase

Stimulated by acetyl-CoA, increasing the rate of gluconeogenesis when the cell has adequate supplies of other substrates (fatty acids) for energy production

Pyruvate>>>Phosphoenolpyruvate (PEP)

Pyruvate is first transported from the cytosol into mitochondria or is generated from alanine within mitochondria by transamination, in which the alpha amino group is transferred from alanine (leaving pyruvate) to an alpha keto carboxylic acid
Then pyruva

Show how NADH is recycled to NAD+ under aerobic conditions and under anaerobic conditions. Why is it important to recycle NADH produced during glycolysis to NAD+?

Cells contain a limited supply of NAD+ and NADH. The oxidation of glyceraldehyde 3-phosphate requires NAD+ as an electron acceptor---it converts NAD+ to NADH. Unless this NADH is recycled to NAD+, oxidative metabolism in this cell will cease for lack of a

Substrate Level Phosphorylation

Phosphorylation of ADP

The conversion of glucose into G6P, which must occur in the breakdown of glucose, is thermodynamically unfavorable (endergonic). How do cells overcome this problem?

Cells often drive a thermodynamically unfavorable reaction in the forward direction by coupling it to a highly exergonic reaction through a common intermediate. To make G6P formation thermodynamically favorable, cells transfer phosphoryl groups from ATP t

Thiomine Pyrophosphate (TPP)

The active coenzyme form of vitamin B1; involved in aldehyde transfer reactions

Two reactions in glycolysis produce ATP. Name the reaction and product, indicate which cofactors participate and where, and name the enzymes

1,3-bisphophate is catalyzed by the enzyme Phosphoglycerate Kinase in which ADP produces ATP with Mg2+ is a cofactor producing 3-Phosphoglycerate & Phosphoenolpyruvate is catalyzed by the enzyme Pyruvate Kinase in which ADP produces ATP with Mg2+ and K+ a

What are the biological functions of the pentose phosphate pathway

The pentose phosphate pathway produces pentose phosphates (for nucleotide synthesis) and NADPH (reducing agent for biosynthetic processes

What are the two reactions in glycolysis in which aldose to ketose isomerization is catalyzed by an enzyme? Briefly explain how the reactions are able to proceed without the input of additional energy

G6P (aldose)>F6P (ketose) & Dihydroxyacetone Phosphate (ketose)>Glyceraldehyde 3-phosphate (aldose)
Although both reactions have standard free energy changes that are positive, they can occur within cells b/c the products are immediately removed by the ne

What is gluconeogenesis, and what useful purpose does it serve in people

Gluconeogenesis is the biosynthesis of glucose from simpler, noncarbohydrate precursors such as oxaloacetate or pyruvate. During periods of fasting, when carbohydrate reservers have been exhausted, gluconeogenesis provides glucose for metabolism in tissue

Which catalyzes a reaction in which ATP is produced

Pyruvate Kinase

Which catalyzes a reaction in which NADH is produced

Glyceraldehyde 3-phosphate

Which of the enzyme represents a major regulation point in glycolysis

Phosphofructokinase-1

Yeast

Regenerate NAD+ by reducing pyruvate to ethanol and CO2