Carbohydrate

Metabolism
Marvin P. Catacutan, RN, LPT
Natural Science Department
College of Arts and Sciences, OLFU-QC
Carbohydrate
Metabolism
• The molecule glucose is the focal point of carbohydrate
metabolism
• Oxidized to yield energy
• Stored as glycogen
• With sufficient oxygen, glucose is oxidized to H2O and
CO2
• In the absence of oxygen, glucose is partially oxidized to
lactic acid
Digestion and Absorption
of Carbohydrates

• Digestion
• The biochemical process by which food
molecules, through hydrolysis, are broken
down into simpler chemical units that can be
used by cells for their metabolic needs
• The first state in the processing of food
products
Digestion and Absorption of Carbohydrates
Digestion and Absorption of
Carbohydrates
• Intestinal walls are lined with villi, fingerlike projections that are rich in blood capillaries
• Absorption is by active transport
Digestion and Absorption of Carbohydrates
Glycolysis
• Glycolysis
• The metabolic pathway by which glucose (a C6 molecule) is converted into two molecules of pyruvate (a C3 molecule),
chemical energy in the form of ATP is produced, and NADH-reduced coenzymes are produced
• Conversion of glucose to pyruvate is an oxidation process in which no molecular oxygen is utilized
• Oxidizing agent is the coenzyme NAD+
• Linear, not cyclic
• Anaerobic pathways
• Molecular oxygen is not a participant
• Aerobic pathways
• Molecular oxygen is a participant
Glycolysis

• Glycolysis
• The ten-step process is enzyme-catalyzed
• Enzymes are present in the cell cytosol
• Glycolysis occurs in the cytosol
 Six-Carbon Stage of Glycolysis (Steps 1-3)

• Six-Carbon Stage
• Energy-consuming stage
• Energy released associated with the conversion of two ATP to two ADP is used
to transform monosaccharides into monosaccharide phosphates
• Intermediates are either glucose of fructose derivatives in which phosphate
groups are present
 • Step 1: Phosphorylation using ATP: Formation of Glucose 6-Phosphate
Six-Carbon Stage of
Glycolysis (Steps 1-3)
• Phosphorylation of glucose to yield glucose 6-phosphate
• Phosphate group is from an ATP molecule
• Hexokinase is an enzyme that requires Mg2+ ion for its activity, catalyzes the reaction
•
•
Requires energy
Glucose (neutral) can cross cell membrane; glucose 6-phosphate (negatively charged)
cannot
 • Step 2: Isomerization: Formation of Fructose 6-Phosphate
• Phosphoglucosisomerase isomerizes glucose 6-phosphate to fructose 6-phosphate

Six-Carbon Stage of • Net result of this change is that carbon 1 of glucose is no longer part of the ring structure
• Glucose (an aldose) forms a six-membered ring

Glycolysis (Steps 1-3) •

•
Fructose (a ketose) forms a five-membered ring
Both contain six carbon atoms
 • Step 3: Phosphorylation using ATP: Formation of Fructose
1,6-Bisphosphate
Six-Carbon Stage of • Requires energy expenditure
Glycolysis (Steps 1-3) • ATP is the source of the phosphate and the energy
• Phosphofructokinase requires Mg2+ ion for its activity
 • Three-Carbon Stage
• Energy-generating
stage
• Intermediates are C2-
phosphates
• Loss of phosphate
from the high-energy
species effects the
conversion of ADP
molecules to ATP
molecules
• C3 intermediates are
phosphorylated
derivatives of
Three-Carbon Stage of dihydroxyacetone,
glyceraldehyde,
Glycolysis (Steps 4-10) glycerate, or pyruvate,
which are derivatives
of glycerol or acetone
Three-Carbon Stage • Step 4: Cleavage: Formation of Two Triose Phosphates
• C6 species is split into two C3 (triose) species

of Glycolysis (Steps • Fructose 1,6-biphosphate is unsymmetrical; thus, two trioses are not identical
• Dihydroxyacetone phosphate

4-10) •
• Glyceraldehyde 3-phosphate
Aldolase catalyzes this reaction
 • Step 5: Isomerization: Formation of Glyceraldehyde 3-Phosphate
Three-Carbon Stage • Dihydroxyacetone phosphate (ketose) and glyceraldehyde 3-phosphate
(aldose) are isomers
of Glycolysis (Steps • Only glyceraldehyde 3-phosphate is a glycolysis intermediate

4-10)
• Dihydroxyacetone phosphate can be converted into glyceraldehyde 3-
phosphate (ketone to aldose) through catalyzation of the enzyme
triosephosphate isomerase
Three-Carbon Stage
• Step 6: Oxidation and Phosphorylation Using Pi: Formation of 1,3-Bisphosphoglycerate
• Phosphate group (high energy phosphate group) is added to glyceraldehyde 3-phosphate
to produce 1,3 biphosphoglycerate by Glyceraldehyde 3-phosphate dehydrogenase

of Glycolysis (Steps • High-energy phosphate group is produced when a phosphate group is attached to a carbon
atom that is also participating in a carbon–carbon or carbon–oxygen double bond

4-10) •
•
Hydrogen of the aldehyde group becomes part of NADH
Source of the added phosphate is inorganic phosphate (Pi)
Three-Carbon Stage
• Step 7: Phosphorylation of ADP: Formation of 3-Phosphoglycerate
• Diphosphate species is converted back to a monophosphate species; thus, an ATP-producing step (substrate level phosphorylation)
• Involved enzyme is phosphoglycerokinase

of Glycolysis (Steps • Substrate-level phosphorylation

• The biochemical process whereby ATP is produced from ADP through direct transfer of a high-energy phosphoryl group from a
reaction substrate to ADP

4-10)
• Oxidative phosphorylation
• Involves production of ATP from ADP using Pi (free phosphate) and the energy “harvested” from the oxidation-reduction
reactions of the electron transport chain
Three-Carbon Stage • Step 8: Isomerization: Formation of 2-Phosphoglycerate
• The enzyme phosphoglyceromutase catalyzes the
of Glycolysis (Steps exchange of phosphate froup from carbon 3 to carbon
2
4-10)
Three-Carbon Stage • Step 9: Dehydration; Formation of Phosphoenolpyruvate
• An alcohol dehydration reaction that proceeds with the enzyme
of Glycolysis (Steps enolase, another Mg2+-requiring enzyme
• Result is another compound containing a high-energy phosphate
4-10) group (phosphate group is attached to a carbon atom that is
involved in a carbon-carbon double bond)
Three-Carbon Stage • Step 10: Phosphorylation of ADP: Formation of Pyruvate
• Substrate phosphorylation occurs

of Glycolysis (Steps • Phosphoenolpyruvate transfers its high-energy phosphate group to an ADP

molecule to produce ATP and pyruvate

4-10) • Pyruvate kinase requires Mg2+ and K+ ions for its activity
• Because two C3 molecules are reacting, two ATP molecules are produced
Glycolysis
Glycolysis
Entry of Galactose and Fructose into
Glycolysis
• Galactose and Fructose are converted, in the liver, to intermediates that enter into the glycolysis
pathway
• Conversion of galactose to glucose 1-phosphate (a four-step sequence) and to glucose 6
phosphate (a glycolysis intermediate)
• Conversion of fructose involves phosphorylation of ATP to produce fructose 1-phosphate, which is
then split into two trioses (glyceraldehyde and dihydroxyacetone phosphate)
• Dihydroxyacetone phosphate enters glycolysis directly
• Glyceraldehyde must be phosphorylated by ATP to glyceraldehyde 3-phosphate
Entry of
Galactose and
Fructose into
Glycolysis
Regulation of Glycolysis
• Control points of glycolysis are steps 1, 3, and 10.
• Step 1
• Hexokinase is inhibited by glucose 6-phosphate
• Step 3
• High concentration of ATP and citrate inhibit phosphofructokinase
• High ATP concentration (=low energy consumption) stops glycolysis at the fructose 6-phosphate stage, which increases
glucose 6-phosphate stores (glucose 6-phosphate is in equilibrium with fructose 6-phosphate)
• Step 10
• High ATP concentration inhibits pyruvate kinase
• Both pyruvate kinase (step 10) and phosphofructokinase (step 3) are allosteric enzymes
Fates of Pyruvate
• Fates of Pyruvate
• Acetyl-CoA Formation
• Requires aerobic condition
• Lactate Formation
• Occurs under anaerobic conditions
• Ethanol Formation
• Occurs under anaerobic conditions
• Limited to some microorganisms
Fates of
Pyruvate
 • Under aerobic condition, pyruvate is oxidized to acetyl-CoA
• Pyruvate formed in the cytosol crosses the two mitochondrial membranes and
enter the mitochondrial matrix, where the oxidation takes place
• Involves both oxidation and decarboxylation (CO2 is produced)
• Requires NAD+. COA-SH, FAD, and two other coenzymes (lipoic acid and thiamin
pyrophosphate)
• Most acetyl CoA molecules produced from pyruvate enter the citric acid cycle.
• Citric acid cycle operations change more NAD+ to its reduced form, NADH.

Oxidation to • The NADH (from glycolysis, from the conversion of pyruvate to acetyl CoA,
and from the citric acid cycle) enters the electron transport chain directly or
indirectly.

Acetyl-CoA • In the ETC, electrons from NADH are transferred to O2, and the NADH is
changed back to NAD+.
• The NAD+ needed for glycolysis, pyruvate–acetyl CoA conversion, and the
citric acid cycle is regenerated.
Fermentation
Processes
• The last step of ETC is oxygen-dependent
• In the absence of oxygen, there is a buildup in NADH
concentration and decrease in the available NAD+
• Decrease NAD+ negatively affects the rate of
glycolysis
• Fermentation
• A biochemical process by which NADH is oxidized to
NAD+ without the need for oxygen
• Lactate fermentation
• Ethanol fermentation
 • Lactate fermentation
• The enzymatic anaerobic reduction of pyruvate to lactate
• Sole purpose is the conversion of NADH to NAD+ (needed
in step 6 of glycolysis)
Lactate • Lactate is converted back to pyruvate when aerobic
condition is established

Fermentation
Ethanol Fermentation
• Ethanol Fermentation
• The enzymatic anaerobic conversion of pyruvate to ethanol and carbon dioxide
• First step in conversion of pyruvate to ethanol is a decarboxylation reaction to produce
acetaldehyde

• Second step involves acetaldehyde reduction to produce ethanol

• Overall equation

• Overall reaction for the production of ethanol from glucose is obtained by combining the reaction
for the conversion of pyruvate with the net reaction for glycolysis
ATP Production • NADH, produced in the cytosol (produced
for the Complete in step 6 of glycolysis), cannot directly
participate in the electron transport chain
Oxidation of because mitochondria are impermeable to
NADH (and NAD+)
Glucose • A transport system shuttles the electrons
from NADH, but not NADH itself, across
the membrane
• This shuttle involves dihydroxyacetone
phosphate (a glycolysis intermediate) and
glycerol 3-phosphate
ATP Production for the
Complete Oxidation of
Glucose
ATP Production for the Complete Oxidation of Glucose
Glycogen • Glycogen
• Branched polymeric form of glucose
Synthesis and • Storage form of carbohydrates in

Degradation humans and animals

• Found primarily in muscle and liver
tissue
• Muscles – source of glucose
needed for glycolysis
• Liver – source of glucose needed
to maintain normal glucose levels
in the blood
Glycogenesis

• Glycogenesis
• The metabolic pathway by which glycogen is synthesized from glucose 6-phosphate
Glycogenesis

• Step 1: Isomerization: Formation of

Glucose 1-phosphate
• Glucose 6-phosphate (from the
first step of glycolysis) is the
starting material, not glucose
• Enzyme phosphoglucomutase
effects the change from a 6-
phosphate to a 1-phosphate
Glycogenesis

• Step 2: Activation: Formation of UDP-

glucose
• UTP (uridine triphosphate)is a
high-energy compound activator
• UMP is transferred to glucose 1-
phosphate, and the resulting PPi is
hydrolyzed to 2Pi.
Glycogenesis

• Step 3: Linkage to Chain: Glucose

Transfer to a Glycogen Chain
• Glucose unit of UDP-glucose is
then attached to the end of a
glycogen chain
• UDP produced in step 3 is
converted back to UTP (can react
with glucose 1-phosphate of step
2); requires ATP
• Requires 2 ATP molecules – for (1)
glucose 6-phosphate formation
and (2) regeneration of UTP
Glycogenolysis

• Glycogenolysis
• The metabolic pathway by which glucose 6-phosphate is produced from glycogen
• Does not require UTP or UDP
Glycogenolysis
• Step 1: Phosphorolysis: Formation of
Glucose-1-phosphate
• Glycogen phosphorylase
removes an end glucose unit
from a glycogen molecule as
glucose 1-phosphate
Glycogenolysis
• Step 2: Isomerization: Formation of
Glucose 6-phosphate
• Phosphoglucomutase catalyzes
the isomerization process
whereby the phosphate group
of glucose 1-phosphate is
moved to the carbon 6 position
Glycogenolysis
• No ATP or any nucleotide triphosphates is needed in
glycogenolysis
• Muscle and brain cells – immediate need for energy is
stimulus for glycogenolysis
• Glucose 6-phosphate that is produced directly
enters the glycolysis pathway
• Lacks glucose 6-phosphatase (cannot form
glucose from glucose 6-phosphate)
• Liver cells – low level of glucose is the stimulus
• Glucose 6-phosphate (cannot cross cell
membrane) produced is converted to free glucose
before it enters the bloodstream
Glycogenesis and Glycogenolysis
Gluconeogenesis

• Gluconeogenesis
• The metabolic pathway by which glucose is synthesized from non- carbohydrate materials
• Occurs in the liver (90%)
• Glycogen store in the liver and muscles is depleted after 12-18 hours
• Noncarbohydrate starting materials:
• Lactate (from hard-working muscles and from RBCs)
• Glycerol (from triacylglycerol hydrolysis)
• Certain amino acids (from dietary protein hydrolysis or muscle starvation during
starvation)
Gluconeogenesis

• Gluconeogenesis involves 12 compounds

• Glycolysis involves 11 compounds
• Last step of glycolysis is the conversion of the high-
energy compound phosphoenolpyruvate to pyruvate
• Reverse of this process (start of gluconeogenesis) cannot
be accomplished in a single step because of the large
energy difference between the two compounds and the
slow rate of the reaction
• A two-step process by way of oxaloacetate is
required to effect the change, and this adds an
extra compound to the gluconeogenesis pathway
• Both an ATP molecule and a GTP molecule are
needed to drive this two-step process.
Gluconeogenesis

• Oxaloacetate intermediate in this two-step process provides a connection to

the citric acid cycle
• Oxaloacetate combines with acetyl CoA
• New enzymes for gluconeogenesis are fructose 1,6-bisphosphatase and
glucose 6-phosphatase
• To reconvert pyruvate to glucose requires the expenditure of 4 ATP and 2
GTP.
 • Cori Cycle
• A cyclic biochemical process in which glucose is
The Cori Cycle converted to lactate in muscle tissue, the lactate is
reconverted to glucose in the liver, and the glucose is
returned to the muscle tissue
Terminology for
Glucose Metabolic
Pathways
The Pentose Phosphate Pathway

• Pentose Phosphate Pathway

• The metabolic pathway by which glucose is used to produce NADPH, ribose 5-
phosphate (a pentose phosphate), and numerous other sugar phosphates
• Has 2 stages – an oxidative stage and a nonoxidative stage
The
Pentose
Phosphate
Pathway • Oxidative Stage of the Pentose Phosphate Pathway
• Involves three steps through which glucose 6-phosphate is
converted to ribulose 5-phosphate and CO2
• Production of two NADPH molecules per glucose 6-phosphate
The
Pentose
Phosphate
Pathway • Nonoxidative stage of the Pentose Phosphate Pathway
• In the first step, ribulose 5-phosphate (a ketose) is isomerized to ribose 5-phosphate (an aldose)
• pentose ribose is a component of ATP, GTP, UTP, CoA, NAD1/NADH, FAD/FADH2, and RNA
• Further steps involve conversion of ribose 5-phosphate to numerous other sugar phosphates
• Glyceraldehyde 3-phosphate and fructose 6-phosphate (both glycolysis intermediates) are
formed
Hormonal Control of Carbohydrate Metabolism
• Insulin
• A 51-amino-acid protein hormone
• Produced by the beta cells of the pancreas
• Promotes the uptake and utilization of glucose by cells
• Function is to lower blood-glucose levels; also involved in lipid metabolism
• Release of insulin is triggered by high blood-glucose levels
• Insulin action involves insulin binding to protein receptors on the outer surfaces of
cells, which facilitates entry of glucose into the cells
• Produces an increase in the rates of glycogenesis, glycolysis, and fatty acid synthesis
Hormonal Control of Carbohydrate Metabolism
• Glucagon
• A polypeptide hormone (29 amino acids) produced in the pancreas by alpha cells
• Released when blood-glucose levels are low
• Principal function is to increase blood-glucose concentrations by speeding up the
conversion of glycogen to glucose (glycogenolysis) and gluconeogenesis in the liver
Hormonal Control of Carbohydrate
Metabolism

• Epinephrine
• Also called adrenaline
• Released by the adrenal glands in response to anger, fear, or
excitement
• Function is similar to that of glucagon— stimulation of
glycogenolysis, the release of glucose from glycogen
• Primary target is muscle cells; also functions in lipid metabolism
• Acts by binding to a receptor site on the outside of the cell
membrane, stimulating the enzyme adenyl cyclase to begin
production of a second messenger, cyclic AMP (cAMP) from ATP
• The cAMP is released in the cell interior, where, in a series of
reactions, it activates glycogen phosphorylase, the enzyme that
initiates glycogenolysis
• Glucose 6-phosphate that is produced from the glycogen
breakdown provides a source of quick energy
B Vitamins and
Carbohydrate Metabolism

• The four vitamins are:

• Niacin (as NAD1, NADH)
• Rboflavin (as FAD)
• Thiamin (as TPP)
• Pantothenic acid (as CoA)
• Two newly involved B vitamins are biotin and
vitamin B6:
• 1. Biotin involvement occurs in the enzyme
pyruvate carboxylate, the enzyme needed to
convert pyruvate to oxaloacetate (the new first
step in gluconeogenesis).
• 2. Vitamin B6 in the form of PLP is involved in
glycogenosis