14| Glucose Utilization and

Biosynthesis
2013 W. H. Freeman and Company

Glycolysis occurs at elevated

rates
in tumor cells Warberg
Effect

Glucose Uptake Is Deficient In

Type 1 Diabetes Mellitus

Fates of Pyruvate

Anaerobic Glycolysis:
Fermentation
Generation of energy (ATP) without consuming
oxygen or NAD+
No net change in oxidation state of the sugars
Reduction of pyruvate to another product
Regenerates NAD+ for further glycolysis under
anaerobic conditions
The process is used in the production of food from
beer to yogurt to soy sauce

Animals undergo
lactic acid fermentation
Reduction of pyruvate to lactate, reversible
During strenuous exercise, lactate builds up in the muscle
Generally less than 1 minute

The acidification of muscle prevents its continuous

strenuous work
The lactate can be transported to the liver and converted
to glucose (gluconeogenesis Cori cycle)
Requires a recovery time
High amount of oxygen consumption to fuel gluconeogenesis
Restores muscle glycogen stores

Lactic Acid Fermentation

The Cori Cycle

Yeast undergo
Ethanol Fermentation
Two-step reduction of pyruvate to ethanol, irreversible
Humans do not have pyruvate decarboxylase
We do express alcohol dehydrogenase for ethanol
metabolism
CO2 produced in the first step is responsible for:
carbonation in beer
dough rising when baking bread

Both steps require cofactors

Pyruvate decarboxylase: Mg++ and thiamine pyrophosphate
(TPP)
Alcohol dehydrogenase: Zn++ and NADH

Ethanol Fermentation

TPP is a common acetaldehyde

carrier
Thiamine pyrophosphate is a coenzyme derived from vitamin B1
Important for cleavage of bonds adjacent to carbonyl group, such
as decarboxylation of -keto acids and in chemical
rearrangements in which an activated acetaldehyde group is
transferred from one carbon to another

Gluconeogenesis:
Precursor for Carbohydrates
Notice that mammals
cannot convert fatty
acids to sugars.

Glycolysis vs. Gluconeogenesis

Glycolysis occurs
mainly in the
muscle and brain.

Gluconeogenesis
occurs mainly in
the liver.

Glycolysis vs. Gluconeogenesis

Opposing pathways that are both
thermodynamically favorable
Operate in opposite direction
end product of one is the starting compound of the other

Reversible reactions are used by both

pathways
Irreversible reaction of glycolysis must be
bypassed in gluconeogenesis
Highly thermodynamically favorable, and
regulated
Different enzymes in the different pathways
Differentially regulated to prevent a futile cycle

Glycolysis vs. Gluconeogenesis

Pyruvate to
Phosphoenolpyruvate

Requires two energy-consuming steps

First step, pyruvate carboxylase converts

pyruvate to oxaloacetate
Carboxylation using a biotin cofactor
Requires transport into the mitochondria, via
malate

Second step, phosphoenolpyruvate

carboxykinase converts oxaloacetate to PEP
Phosphorylation from GTP and decarboxylation
Occurs in mitochondria or cytosol depending on
the organism

Synthesis of Oxaloacetate

Biotin is a CO2 Carrier

Biotin is used as a carrier of activated bicarbonate
Reaction occurs in two phases at different sites of the
enzyme
At catalytic site 1, bicarbonate is converted to CO2, at
the expense of ATP
Long biotinyl-Lys tether moves CO2 to site 2 on the
enzyme surface, where it is released and reacts with
pyruvate forming oxaloacetate

Pyruvate to
Phosphoenolpyruvate

Requires two energy-consuming steps

First step, pyruvate carboxylase converts

pyruvate to oxaloacetate
Carboxylation using a biotin cofactor
Requires transport into the mitochondria, via
malate

Second step, phosphoenolpyruvate

carboxykinase converts oxaloacetate to PEP
Phosphorylation from GTP and decarboxylation
Occurs in mitochondria or cytosol depending on
the organism

Oxaloacetate to
Phosphoenolpyruvate

From Pyruvate to
Phosphoenolpyruvate

Additional Bypasses
Catalyze reverse reaction of opposing step in
glycolysis
Are irreversible themselves
Fructose 1,6-bisphosphate Fructose 6Phosphate
By fructose bisphosphatase-1
Coordinately/oppositely regulated with
Phosphofructokinase-1

Glucose 6-phosphate Glucose

By glucose 6-phosphatase

Glycolysis vs. Gluconeogenesis

Gluconeogenesis is expensive
2 Pyruvate + 4 ATP + 2 GTP + 2 NADH + 2 H+ + 4
H2O
Glucose + 4 ADP + 2 GDP + 6 Pi
Costs
+
2 NAD+4 ATP, 2 GTP, and 2 NADH

But physiologically necessary

Brain, nervous system, and red blood cells

generate ATP ONLY from glucose
When glycogen stores are depleted we
need to get glucose from somewhere
During starvation or vigorous exercise

Precursors for
Gluconeogenesis
Animals can produce glucose from sugars
or proteins

Sugars: pyruvate, lactate, or oxaloacetate

Protein: from amino acids that can be converted
to citric acid cycle intermediates (or glucogenic
amino acids)

Animals cannot produce glucose from fatty

acids

Product of fatty acid degradation is acetyl-CoA

Cannot have a net converstion of acetyl-CoA to
oxaloacetate
Plants, yeast, and many bacteria can do this,
thus producing glucose from fatty acids

Pentose Phosphate Pathway

Pentose Phosphate Pathway

The main products are NADPH and ribose 5-phosphate
NADPH is an electron donor
Reductive biosynthesis of fatty acids and steroids
Repair of oxidative damage

Ribose-5-phosphate is a biosynthetic precursor of nucleotides

Used in DNA and RNA synthesis
Or synthesis of some coenzymes

Oxidative phase generates

NADPH and Ribose-5Phosphate

regenerates Glucose
-6-Phosphate from Ribose-5requiring more NADPH than R-5-P
Used in tissuesPhosphate
Such as the liver and adipose tissue

NADPH regulates partitioning

into glycolysis vs. pentose
phosphate pathway

Glucose-6-Phosphate
Dehydrogenase Deficiency
Can be fatal in cases of high oxidative stress
Certain drugs, herbicides, and some foods

Resistance to malaria due to high oxidative

stress in red blood cells

Chapter 14:
Summary

In this chapter, we learned:

Glycolysis, a process by which cells can extract a limited

amount of energy from glucose under anaerobic
conditions
Gluconeogenesis, a process by which cells can use a
variety of metabolites for the synthesis of glucose
The differences between glycolysis and gluconeogenesis
How they are both made thermodynamically favorable
How they are differentially regulated to avoid a futile cycle

Pentose phosphate pathway, a process by which cells

can generate reducing power (NADPH) that is needed for
the biosynthesis of various compounds