Spencer L. Seager
Michael R. Slabaugh
www.cengage.com/chemistry/seager
Chapter 23:
Carbohydrate Metabolism
Jennifer P. Harris
CARBOHYDRATE METABOLISM (DIGESTION)
• The main reaction of carbohydrate digestion to
monosaccharides is hydrolysis:
CARBOHYDRATE METABOLISM (continued)
• Carbohydrates:
• account for 45-55% of daily energy needs in the typical
American diet.
• are digested into glucose, fructose, and galactose, which
are absorbed into the bloodstream through the lining of
the small intestine and transported to the liver.
• In the liver, fructose and galactose are rapidly converted to
glucose or compounds that are metabolized by the same
pathway as glucose.
Glucose Metabolism Overview
Glycogen
Glycogenesis
High glucose present, β
cells in pancreas
realease insulin
Ribose
RNA
Polysaccharide
Energy Storage
Glycogenolysis
Muscles need energy or
fear, anger conditions or
absence of glucose
Glucose
Gluconeogensis
During starvation 
breakdown of proteins
from muscle cells
Glycolysis
10 step process
Pyruvate
Energy
BLOOD GLUCOSE LEVELS
• Blood glucose levels are:
• also known as blood sugar
levels.
• measured after a fast of 8-12
hours.
• highest about 1 hour after a
carbohydrate-containing meal.
• returns to normal after 2-2½
hours.
• regulated by the liver.
• Hypoglycemia is a blood sugar
level below normal fasting level.
• Hyperglycemia is a blood sugar
level above normal level.
BLOOD GLUCOSE LEVELS (continued)
• The renal threshold is:
• a blood sugar level above 180 mg/100 mL.
• the blood sugar level at which the sugar not completely
reabsorbed by the kidneys.
• exceeded when glucose is excreted in the urine, a
condition called glucosuria.
• Prolonged hyperglycemia at glucosuric levels:
• is considered serious.
• means something is wrong with the body’s normal ability
to control blood sugar level.
BLOOD GLUCOSE LEVELS (continued)
• The liver is the key organ in regulating the blood
glucose levels.
• It responds to increase in blood glucose after a meal
by removing glucose from bloodstream.
• The removed glucose is converted to glycogen or
triglycerides.
• When blood glucose levels are low, glycogen is
converted to glucose.
GLYCOLYSIS
• Glucose (C6) is catabolically oxidized through a many step
process to pyruvate (C3).
• In addition to the two molecules of pyruvate, two molecules
of ATP, two molecules of NADH, four molecules of H+, and
two molecules of H2O are produced.
• Glycolysis occurs in the cellular cytoplasm.
• Net reaction for glycolysis:
GLYCOLYSIS
(continued)
GLYCOLYSIS
(continued)
GLYCOLYSIS
(continued)
• Fructose enters glycolysis as dihydroxyacetone phosphate
and glyceraldehyde-3-phosphate.
• Galactose enters glycolysis as glucose-6-phosphate.
GLYCOLYSIS – REGULATION
• Several steps of the glycolysis pathway are regulated:
• Glucose-6-phosphate competitively inhibits hexokinase
(feedback inhibition).
• The allosteric enzyme phosphofructokinase is inhibited by
ATP and citrate and activated by ADP and AMP.
• The allosteric enzyme pyruvate kinase is inhibited by ATP.
• As glycolysis occurs, so does the citric acid cycle and
electron transport chain which produce ATP.
• If the ATP level is low, then AMP and ADP levels are high.
GLYCOLYSIS – REGULATION (continued)
THE FATES OF PYRUVATE
• After glycolysis, pyruvate can be:
• oxidized to acetyl CoA (aerobic conditions).
• reduced to lactate (anaerobic conditions).
• reduced to ethanol (anaerobic conditions for some
prokaryotic organisms).
• Note: All processes must regenerate NAD+ from NADH so
glycolysis can continue.
THE FATES OF PYRUVATE (continued)
PYRUVATE OXIDATION TO ACETYL CoA
• Pyruvate oxidation to acetyl CoA occurs in the mitochondria.
• Most of the acetyl CoA will be completely oxidized to CO2 in
the citric acid cycle.
• Some acetyl CoA will serve as starting material for fatty acid
biosynthesis.
• NAD+ is regenerated when NADH transfers its electrons to
O2 in the electron transport chain.
PYRUVATE REDUCTION TO LACTATE
• Pyruvate reduction to lactate occurs in cells after strenuous
or long-term muscle activity because the cellular supply of
oxygen is not adequate for the reoxidation of NADH to NAD+.
• Under anaerobic conditions, animals and some
microorganism can obtain limited energy through lactate
fermentation.
PYRUVATE REDUCTION TO ETHANOL
• Under anaerobic conditions, some microorganisms can
obtain limited energy through glycolysis and the two step
conversion of pyruvate to ethanol.
• Overall equation:
• Step-wise equations:
THE CITRIC ACID CYCLE
• The citric acid cycle:
• has other names, including:
• the tricarboxylic acid cycle.
• the Krebs cycle.
• is the principle process for generating the reduced
coenzymes NADH and FADH2.
• is the source of intermediates for biosynthesis.
• occurs within the matrix of the mitochondrion.
• includes eight reactions.
THE CITRIC ACID CYCLE (continued)
• Pyruvate oxidized to acetyl CoA can enter the citric acid
cycle where it will be further oxidized to two molecules of
CO2, producing one molecule of GTP and the reduced forms
of three molecules of NAD+ (NADH) and one molecule of
FAD (FADH2) which can then enter the electron transport
chain to produce ATP.
• The overall reaction is:
THE CITRIC ACID CYCLE (continued)
THE CITRIC ACID CYCLE (continued)
THE CITRIC ACID CYCLE (continued)
CITRIC ACID CYCLE – REGULATION
• There are three main points of regulating citric acid cycle
activity.
• Citrate synthetase is an allosteric enzyme for the first step
of the cycle is inhibited by ATP and NADH and activated
by ADP.
• Isocitrate dehydrogenase is an allosteric enzyme for the
third step of the cycle is inhibited by NADH and activated
by ADP.
• a-Ketoglutarate dehydrogenase complex is a group of
allosteric enzymes for the fourth step of the cycle is
inhibited by succinyl CoA, NADH, and ATP.
• The rate of citric acid cycle is reduced when cellular ATP
levels are high.
• The rate of citric acid cycle is increased when ATP supplies
are low and ADP levels are high.
CITRIC ACID CYCLE – REGULATION
(continued)
THE ELECTRON TRANSPORT CHAIN
• NADH and FADH2 are produced by the citric acid cycle.
• They enter the electron transport chain where they can be
used to supply hydrogen ions and electrons to reduce
oxygen to water.
• Net equation:
4H+ + 4e− + O2 → 2H2O
• The electron transport chain occurs in a series of reactions.
THE ELECTRON TRANSPORT CHAIN
(continued)
• The electron transport chain is found in the inner
membrane of the mitochondria and involves iron-containing
enzymes (cytochromes).
• Generated NAD+ and FADH enter citric acid cycle again
• Electron carriers are lined up in increasing electron affinity
THE ELECTRON TRANSPORT CHAIN
(continued)
• As electrons are
transported along the
electron transport
chain, a significant
amount of free energy
is released (52.6
kcal/mol).
• Some free energy is
conserved in oxidative
phosphorylation
(production of ATP from
ADP and Pi).
• Approx. 25% - 34% of
energy is conserved
OXIDATIVE PHOSPHORYLATION:
CHEMIOSMOTIC HYPOTHESIS
• The chemiosmotic hypothesis states that the electron
transport chain pumps H+ across the inner mitochondrial
membrane, H+ then flows back across the membrane,
causing the formation of ATP by F1-ATPase.
• Oxidative phosphorylation conserves approximately 34%
of the energy released from the electron transport chain for
each mole of NADH.
• Oxidative phosphorylation conserves approximately 25%
of the energy released from the electron transport chain for
each mole of FADH2.
OXIDATIVE PHOSPHORYLATION:
CHEMIOSMOTIC HYPOTHESIS
OXIDATIVE PHOSPHORYLATION FROM
ELECTRON TRANSPORT
• The conversion of NADH to NAD+ generates 2.5 ATP from
ADP during oxidative phosphorylation.
• The conversion of FADH2 to FAD generates 1.5 ATP from
ADP during oxidative phosphorylation.
• The energy yield for the entire catabolic pathway (citric acid
cycle, electron transport chain, and oxidative
phosphorylation combined):
THE COMPLETE OXIDATION OF GLUCOSE
• NADH produced in cytoplasm does not pass through the
mitochondrial membrane to the site of the electron
transport chain.
• Brain and muscle NADH employ a transport mechanism that
passes electrons from cytoplasm NADH through the
membrane to FAD molecules inside mitochondria.
• Cytoplasmic NADH generates only 1.5 molecules of ATP.
• Liver, heart, and kidney cytoplasmic NADH have a more
efficient shuttle that results in one molecule mitochondrial
NADH (and 2.5 molecules ATP) for every cytoplasmic NADH.
THE COMPLETE OXIDATION OF GLUCOSE
(continued)
• Free energy available in glucose:
• Free energy stored in the synthesis of ATP:
• Free energy from the complete oxidation of glucose:
THE COMPLETE OXIDATION OF GLUCOSE
(continued)
• The efficiency of the complete oxidation of glucose:
energy stored
234 kcal/mol
 100 
 100  34.1%
energy available
686 kcal/mol
• Living cells can capture 34% of the released free energy and
make it available to do biochemical work.
• Automobile engines make available 20-30% of the energy
actually released by burning gasoline.
THE COMPLETE OXIDATION OF GLUCOSE
(continued)
GLYCOGEN METABOLISM – SYNTHESIS
• The synthesis of glycogen from glucose (glycogenesis)
involves UTP.
• Glycogen metabolism can occur in all cells, but is an
especially important function of liver and muscle cells.
• Glycogen is mainly stored in liver and muscle tissue.
• The liver can store 110 g glycogen.
• The muscles can store 245 g glycogen.
GLYCOGEN METABOLISM – BREAKDOWN
• During glycogenolysis, glycogen can be broken down to
glucose monomers via its a(1→4) and a(1→6) linkages.
• Glycogenolysis occurs in the liver, kidney, and intestinal
cells, but not in the muscle cells.
(glucose)n + Pi → (glucose)n−1 + glucose 1-phosphate
glycogen
glycogen with one
fewer glucose unit
glucose 1-phosphate ⇆ glucose 6-phosphate
• Glucose 6-phosphate can then be catabolized by the
glycolysis pathway.
glucose 6-phosphate + H2O → glucose + Pi
GLYCOGEN METABOLISM – BREAKDOWN
(continued)
• Muscle cells:
• cannot form free glucose from glycogen.
• can carry out the first two steps of glycogenolysis to
produce glucose-6-phosphate, which:
• is the first intermediate in glycolysis pathway.
• can be used to produce energy.
• utilize glycogen only for energy production.
• The liver:
• maintains a relatively constant level of blood glucose.
• has capacity to degrade glycogen all the way to glucose,
which is released into the blood during muscular activity
and between meals.
GLUCONEOGENESIS
• Gluconeogenesis:
• is the synthesis of glucose from noncarbohydrate
molecules.
• synthesizes glucose from lactate, certain amino acids, and
glycerol.
(lactate, certain amino acids, glycerol) → pyruvate → glucose
• primarily occurs in the liver (~90%).
• does not occur much in the kidneys, brain, skeletal
muscle, or heart, even though these organs have a high
demand for glucose.
THE CORI CYCLE
• Under anaerobic conditions, lactate produced by muscles is
reconverted to glucose by the liver through the Cori Cycle.
• During active exercise:
• lactate levels increase in muscle tissue and lactate
diffuses into the blood;
• lactate is taken to liver and converted back to pyruvate;
• pyruvate is converted to glucose by gluconeogenesis;
• and glucose enters the blood and returns to the muscles.
THE CORI CYCLE (continued)
SUMMARY OF MAJOR PATHWAYS
IN GLUCOSE METABOLISM
HORMONAL CONTROL OF
CARBOHYDRATE METABOLISM
• Three main hormones control carbohydrate metabolism:
• insulin, which:
• decreases blood glucose levels.
• increases absorption of glucose by cells.
• increases the synthesis of glycogen, fatty acids, and
proteins.
• stimulates glycolysis.
• glucagon, which:
• increases blood glucose levels.
• activates glycogen breakdown in liver.
• epinephrine, which:
• increases blood glucose levels.
• stimulates glycogen breakdown in muscle.
HORMONAL CONTROL OF
CARBOHYDRATE METABOLISM (continued)
• Biochemical balance is maintained between the stored
glycogen level and the blood sugar level by two opposing
hormones, insulin and glucagon.
HORMONAL CONTROL OF
CARBOHYDRATE METABOLISM (continued)