BIOCHEMISTRY

2.02 OXIDATION OF HEXOSES

Dr. Reyes | September 23, 2016
LE 2
I.
OUTLINE

Overview of Glycolysis
II. PHASES OF GLYCOLYSIS
2
 Ten-step linear pathway in which ATP is consumed in the
II. Phases of Glycolysis first five steps (energy investment phase) and produced
III. Reaction Steps of Glycolysis in the last five (energy pay-off phase)
a. First Phase
b. Second Phase
IV. Fates of Pyruvate A. First Phase
V. Ways of Reoxidizing NADH  Investment Phase
VI. Other Functions of Glycolysis  Use of 2 ATP  Phosphorylated forms of intermediates
VII. Regulation of Glycolysis
o Glucose  G-6-P
VIII. Inherited Defects of Glycolysis
IX. ATP Yield of Glycolysis o F-6-P  F-1,6-P
a. Aerobic Glycolysis  Phosphorylation: traps intermediates in the cell
b. Anaerobic Glycolysis o No transport systems for sugar phosphates
X. Metabolism of Other Hexoses in mammalian cell plasma membranes
XI. Metabolism of Galactose o also needed to destabilize molecule to
XII. Disorders of Galactose Metabolism
continue the pathway
XIII. Metabolism of Fructose
XIV. Other Information
XV. Polyol or Sorbitol Pathway
XVI. Disorders of Fructose Metabolism
a. Enzyme Deficiencies
b. Substrate Overproduction
XVII. Mannose Metabolism

OBJECTIVES:
At the end of the lecture, the student should be able to discuss
glycolysis in terms of the following:
I. Sites, functions, types, and phases
II. Interconversion steps/sequence of reaction
III. Enzymes and energetics involved
IV. Regulatory Controls
V. Products and ATP Yield

I. OVERVIEW OF GLYCOLYSIS

A. Glycolysis

 Employed by all tissues for breakdown of glucose to

provide energy (Champe, et al.)
 Some free energy released from glucose is conserved in
the form of ATP and NADH
 Other name
o Embden-Meyerhof Pathway: Scientist who first
elucidated the reaction (in muscles)
 Function
o Major pathway for breaking down of sugars,
particularly 6-carbon sugars to provide ATP
 Site: Cytosol / Cytoplasm Types
 Types
o Aerobic – pyruvate is the end product
o Anaerobic – lactate is the end product (e.g
Erythrocytes)

Figure 1. Overview of glycolysis with an emphasis of the 2

phases.

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STEP 2: Isomerization of Glucose-6-Phosphate to

B. Second Phase Fructose-6-Phosphate
 Payoff Phase (G-6-P  F-6-P)
 Production of ATP
 1 molecule glucose: 4 ATP produced
o Net yield: 2 ATP

III. REACTION STEPS IN GLYCOLYSIS

A. First Phase

STEP 1: Phosphorylation of Glucose to Glucose-6-

Phosphate
(Glucose  G-6-P)

 Enzyme: Glucose-6-Phosphate Isomerase

(Phosphohexose Isomerase)
 Cofactor: Mg
2+

 Reaction:
o Reversible
o Aldose-Ketose Isomerization
 C1 aldehyde group  hydroxyl group
 C2 hydroxyl group  ketone group
*Other hexoses can enter by direct conversion to fructose 6-
phosphate, bypassing the steps catalyzed by
 Enzyme: Hexokinase (present in all cells) hexokinase/glucokinase and glucose 6-phosphate isomerase.
o Glucokinase/Hexokinase IV (isozyme of
hexokinase in liver and pancreatic cells) STEP 3: Phosphorylation of Fructose-6-Phosphate to
 Cofactor: Mg
2+ Fructose-1,6-Bisphophate
2+
o Most kinases require Mg for their activity (F-6-P  F-1,6-BP)
 Reaction:
o Highly exergonic
o Phosphorylation
o ATP as the phosphate donor
st
o 1 irreversible reaction

* Kinases (transferase) are ATP-dependent enzymes that

transfer a phosphate group from ATP to another substrate

 Enzyme: Phosphofructokinase-1 (PFK-1)

 Cofactor: Mg
2+

 Reaction:
o Irreversible, Exergonic
o Phosphorylation
o Critical, commitment step of the pathway
 Rate-limiting
nd
o 2 regulatory step of glycolysis

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STEP 4: Cleavage of Fructose 1,6-Bisphosphate into B. Second Phase

Glyceraldehyde-3-Phosphate (GADP) and Dihydroacetone  Each reaction is done twice since 2 GADP molecules
Phosphate (DHAP)
continue the pathway
(F-1,6-BP  DHAP + GADP)
STEP 6: Oxidation and Phosphorylation of
Glyceraldehyde-3-Phosphate to 1,3-Bisphosphoglycerate
(GADP  1,3-BPG)

 Ezyme: Aldolase (Fructose 1,6-biphosphate Aldolase)

 Reaction:
o Reversible
o Cleavage of a C6 sugar into two C3 sugar (triose)
 Enzyme: Glyceraldehyde-3-phosphate dehydrogenase
 Reaction:
STEP 5: Interconversion of GADP and DHAP o Reversible, Endergonic
+ +
(DHAP  GADP) o Participation of NAD and H
o 1,3-BPG: High phosphate energy compound (~P)
 first one generated for glycolysis
o Only redox reaction in glycolysis

 Enzyme: Triose phosphate Isomerase

 Reaction:
o Reversible
o Aldose-ketose isomerization
o With the transformation of DHAP to GADP
 Sulhydryl reagents (Hg and Ag ) and alkylating agents
2+ 2+
 one molecule glucose  two molecules GADP
(iodoacetate)
o Prevents hemithioacetal linkage between GADP and
enzyme active site

 Hyperglycemia
o Overproduction of reactive O2 species that activate
poly (ADP-ribose) polymerase (PARP)

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 Arsenate
o Prevents synthesis of ATP without stopping glycolysis
o Arsenate quickly hydrolyzes into 3-phosphoglycerate
with no production of ATP -> uncouples glycolysis

NOTE: 20% of 1,3-BPG is converted to 2,3-BPG via

phosphoglycerate mutase and bypasses the
phosphoglycerate kinase reaction
*Similar to Pi, if 3-phosphate dehydrogenase reaction  2,3-BPG --hydrolysis--> 3-PG + Pi via 2,3-BPG
participates, the compound will be produced but not as phosphatase
effective  The Rappaport-Lueberring Shunt in RBCs bypasses an
energy-generating step of glycolysis hence ATP
STEP 7: Transfer of Phosphate from 1,3- generation is reduced
bisphophoglycerate onto ADP, forming ATP an 3-  Provides a regulated supply of 2,3-BPG to RBCs  binds
Phosphoglycerate to hemoglobin  decrease O2 affinity
(1,3-BPG  3-PG)
STEP 8: Isomerization of 3-Phosphoglycerate to 2-
Phosphoglycerate

 Enzyme: Phosphoglycerate Mutase

 Coenzyme: Mg
2+

 Reaction:
 Enzyme: Phosphoglycerate kinase (PGK) o Reversible, Endergonic
 Reaction: o 3-PG’s remaining phosphate group does not have
o Reversible, endergonic enough energy to phosphorylate ADP
o Phosphate group from acyl phosphate to ADP, o Isomeration and dehydration
o Substrate level phosphorylation o 2,3 bisphosphoglycerate=possible intermediate
o “Break even point of glycolysis”: 2 molecules of ATP
replace the priming ATP molecules NOTE: A “mutase” is a class of enzymes that move an -R
group from one position in the molecule to another position in
that molecule.

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STEP 9: Dehydration of 2-Phosophoglycerate to Remember: Kinase transfers phosphate group; there is still the
2+
Phosphoenolpyruvate Mg participation in this reaction
(2-PG  PEP)
•  Oxidative
• Occurs only in the electron transport chain
• O2 is used to oxidize carriers NADH to create ATP

IV. FATES OF PYRUVATE

 Pyruvate can be converted to different molecules

depending on the condition that it is presented with
(Anaerobic or Aerobic)

 Enzyme: Enolase or 2-phosphoglycerate dehydratase

 Coenzyme: Mg
2+

 Reaction:
o Produces high-energy phosphate compound (PEP)
 Fluoride inhibition: competitive inhibition
2+
o Forms ionic complex with Mg and Pi in the enzyme’s
active site

STEP 10: Transfer of Phosphate of Phosphoenolpyruvate

(PEP  pyruvate)

A. Pyruvate to Acetyl CoA

 Enzyme: Pyruvate Kinase

 Coenzyme: K , Mg
+ 2+

 Reaction:
o Irreversible, Exergonic
o Substrate level phosphorylation  Aerobic conditions
 Hemolytic anemia can occur if there is deficiency  Using Pyruvate Dehydrogenase
 Krebs cycle: oxidization to CO2 and H2O
NET REACTION:  Occurs in the Inner Mitochondrial Membrane
+
Glucose + 2 NAD + 2 Pi + 2 ADP → 2 pyruvate + 2 NADH + 4 o Inner mitochondrial membrane is not permeable to
+
H + 2 ATP + 2 H2O NADH at basic form hence, shuttles are used so it can
be utilized by ETC
NOTE: Oxidative VS Substrate Level Phosphorylation  Two different shuttles: location of tissues
•  Substrate Level Phosphorylation: determines predominant shuttle
• Occurs in glycolysis and TCA cycle  Malate-Aspartate Shuttle
• Direct transfer of a phosphate group from a substrate o 1 NADH = 2.5 ATP
to ADP catalyzed by kinases o Predominant in skeletal muscles

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 Glycerol Phosphate Shuttle V. WAYS OF REOXIDIZING NADH

o 1 NADH = 1.5 ATP
o Predominant in the liver

B. Reduction of Pyruvate to Lactate

 Constant supply of NAD ensures glycolysis continuation

+

 Anaerobic conditions: reduction of pyruvate to lactate 


 Anaerobic conditions  Aerobic conditions: TCA cycle and mitochondrial
 Via Lactate Dehydrogenase oxidative phosphorylation 

 Simply put: Occurs when vigorous contracting muscles
function under low oxygen conditions (hypoxia)
VI. OTHER FUNCTIONS OF GLYCOLYSIS
 Pyruvate is reduced to lactate
o Accepts electrons from NADH
o Allows regeneration of NAD+ for the continuation of
glycolysis
 Cramps with burning sensation
o Accumulation of lactic acid

C. Conversion of Pyruvate to Ethanol

 Via Pyruvate Decarboxylase

 Mammals lack the pyruvate decarboxylase enzyme
 Occurs in: saccharomyces (yeast cells), plant tissues,
certain invertebrates, protists, and other microorganisms  Generates precursors for biosynthetic processes via
o Pathway in beer and bread manufacturing various glycolytic intermediates
o Brewery: carbonate the final alcoholic brew, this gas  Glucose can be converted to:
produces the foamy head o Glucose-6-phosphate  Ribose 5-phosphate via the
o Bakery: causes the bread dough to rise Hexose Monophosphate Shunt
o Auto brewery Syndrome o Glycerol phosphate  triacyglycerol (TAG)
 A condition where a person gets intoxicated after o Acetyl CoA  fatty acids
they eat carbohydrates o 1,3-BPG  2,3-BPG which functions as:
 Extraordinary amount of yeast cells in the body  an intermediate in the conversion of 3-PG to 2-PG
 3-PG and pyruvate can be used to
D. Carboxylation of Pyruvate to Oxaloacetate produce amino acids
 Via pyruvate carboxylase  Intermediates in TCA that can provide
fuel for glutamate and other amino acids
 Oxaloacetate is an intermediate of Krebs Cycle and
gluconeogenesis
 Allosteric effector of oxygen release in RBCs

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VII. REGULATION OF GLYCOLYSIS  Inherited Pyruvate Dehydrogenase Deficiency

 Defects in one or more of the components of enzyme
 Reactions of glycolysis are reversible, but must be complex
considered physiologically irreversible.  Present with lactic acidosis (after glucose load)
 3 enzymes that catalyze the irreversible or nonequilibrium  Can cause neurologic disturbances
reactions
 Hexokinase or glucokinase (step 1) IX. ATP YIELD OF GLYCOLYSIS
 Phosphofructokinase I (step 3)
o Allosteric feedback regulation Table 1. ATP Yield of Glycolysis (per glucose molecule)
o Inhibited at intracellular conc. of ATP
Reaction ATP
 Pyruvate kinase (step 10)
Glucose  G-6-P -1
o Inhibited by ATP
F-6-P  F-1,6-BP -1
 There is a reciprocal regulation of glycolysis and
GADP  3-PG +2
gluconeogenesis PEP  Pyruvate +2
o Glycolysis “on”: Gluconeogenesis “off” Net ATP Production +2
o Glycolysis “off”: Gluconeogenesis “on”
 Otherwise, a futile cycle would be present
Table 2. Generation and Consumption of ATP in AEROBIC
Glycolysis
VIII. INHERITED DISORDERS OF GLYCOLYSIS
ATP
Phosphoglycerate kinase +2
 Primarily due to genetic deficiencies of glycolytic
Pyruvate kinase +2
enzymes
Oxidative phosphorylation from 2 NADH +5
 Hemolytic Anemia via malate-aspartate shuttle system
Glucokinase/Hexokinase and -2
 Aldolase A and pyruvate kinase deficiencies in
phosphofructokinase-1
erythrocytes
Net ATP +7

 Pyruvate Kinase Deficiency

Table 3. Generation and Consumption of ATP in
 Second most common cause of enzyme deficiency- ANAEROBIC Glycolysis
st
related hemolytic anemia (1 is glucose 6-phosphate ATP
dehydrogenase deficiency) Phosphoglycerate kinase +2
 Restricted to the erythrocytes, accounting for 95% of all Pyruvate kinase +2
inherited defects in glycolytic enzymes.
Glucokinase/Hexokinase and -2
 Deficiency of pyruvate kinase (decreased ATP phosphofructokinase-1
synthesis) > normal biconcave and flexible RBC shape is Net ATP +2
altered > increased phagocytosis of RBCs by the
reticuloendothelial system > premature death and lysis of
RBCs > hemolytic anemia
X. METABOLISM OF OTHER HEXOSES
 Low Exercise Tolerance
 Fructose, Galactose, and Mannose are important sources
 Deficient muscle phosphofructokinase (PFK1) 
of energy, like glucose
decreased ATP synthesis = low exercise tolerance in
 Initial phosphorylation is needed for these to be
patients
trapped inside the cell and to be metabolically useful –
kinases catalyze phosphorylation
 Thiamine Deficiency
 Pyruvate accumulates
 In alcoholics because alcohol inhibits thiamine
absorption

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 Galactose 1-Phosphate (catalyzed by Galactose

Phosphate Uridyl Transferase)  UDP-Galactose
(catalyzed by Lactose Synthetase)  lactose sugar 


 Glucose 1-Phosphate  UDP Gluocse (catalyzed by

Galactose 1-Phosphate Uridyl Transferase)  Glucose 1-
Phosphate (catalyzed by Phosphoglucomutase) 
Glucose 6-Phosphate  Pyruvate  Glycolysis 


 Glucose 1-Phosphate  UDP Gluocse (catalyzed by

Galactose 1-Phosphate Uridyl Transferase)  Glucose 1-
phosphate (catalyzed by Phosphoglucomutase) 
Glucose 6-Phosphate  Glucose  Glycogenolysis 


 Galactose (catalyzed by Galactokinase)  Galactose 1-

Phosphate Phosphate (catalyzed by Galactose 1-
Figure 3. Overview of Galactose, Fructose, and Mannose
Phosphate Uridyl Transferase)  UDP-Galactose 
Metabolism
Glycolipids, Glycoproteins, Glycosaminoglycans 


A. Galactose
 Galactose (catalyzed by Galactokinase)  Galactose-1-
Phosphate (helped by UDP Galactose)  Glucose-6-
Phosphate

B. Mannose
 Mannose (catalyzed by hexokinase)  Mannose-6-
Phosphate (catalyzed by Phosphomannose isomerase)
 Fructose-6-Phosphate (enters glycolytic pathway)

C. Fructose
 Derived from Sucrose
 Fructose bypasses the main regulatory step in glycolysis,
catalyzed by phosphofructokinase, and stimulates fatty Figure 2. Metabolism of Galactose.
acid synthesis and hepatic triacylglycerol secretion
 Has two pathways:
o First Route
 Fructose (Metabolized in muscle, kidney, adipose
tissue; catalyzed by Hexokinase)  -6-
Phosphate
o Second Route
 Preferred pathway
 Major route in the liver
 Fructose (catalyzed by Fructokinase) Fructose-1-
Phosphate  DHAP (enter glycolytic pathway)
 

OR
 Fructose (catalyzed by Fructokinase)  Fructose-1-
Phosphate  (catalyzed by Aldolase B) 
Glyceraldehyde  DHAP
Figure 3. Synthesis of Glucose from Galactose
XI. METABOLISM OF GALACTOSE
Galactose (acted by Galactokinase)  Galactose-1-
 Galactose(catalyzedbyGalactokinase)  Galactose 1- Phosphate (acted by Galactose-1-Phosphate uridly
Phosphate transferase)  UDP Galactose (acted by UDP Galactose-4-
Epimerase)  4-keto-UDP Galactose 
 (intermediate)  UDP

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Glucose  Glycogen  Glucose- 1-Phosphate  Glucose-6- B. Non-classic Galactosemia

Phospate  Glucose

XII. DISORDERS OF GALACTOSE METABOLISM

A. Classical Galactosemia

 Deficiency in Galactokinase
 Galactosuria – high galactose in urine
 Galactosemia – high galactose in blood
 Genetic absence of Galactose-1-Phosphate Uridyl  Galactitol accumulates if galactose is present
Transferase enzyme
 Patient can control sugar intake so he/she will have lower
 More severe than non-classical risk of developing cataract
 Best known deficiency.
 Accumulation of substrate that did not undergo enzymatic C. Non-classical Galactosemia
reaction: Galactose-1-phosphate
 Leads to formation of cataract because of Galactitol
accumulation in tissues especially in lens of the eyes
 Galactose also accumulates in blood and urine and is
reduced to Galactitol.
 Predominance of Aldose reductase
 Galactose (reduced by aldose reductase) to Galactitol
 Galactitol – high affinity for tissues especially the lens of
the eyes
 Galactose-1-phosphate accumulation also depletes the
liver of inorganic phosphate and causes liver failure and
mental deterioration.
 In uridyl transferase deficiency, the UDP Galactose-4-
epimerase is present in adequate amounts, so that the
galactosemic individual can still form UDP Galactose from
glucose.
 Deficiency of β-Galactosidase or Lactase that help in
 UDP Galactose is used in the synthesis of lactose in the
digestion
mammary gland and in other tissues where it is required
 Dietary lactose is not significantly hydrolyzed and
for the synthesis of glycolipids, proteoglycans, and
absorbed; it stays in the intestinal tract
glycoproteins
 Intestinal bacteria metabolize lactose into gases like
 This explains how it is possible for normal growth and
CO2, H2, and short chain acids
development of affected children to occur despite the
galactose-free diets used to control the symptoms of the  Production of osmotic diarrhea
disease.  Common in premature infants, those which have stomach
surgery, mucosal damage after chronic bout of diarrhea
 Milk and their products should be avoided
 Yoghurt can be tolerated in some because lactose has
been partially hydrolyzed via endogenous β-
galactosidase of microorganism in yoghurt culture
 Commercial preparations of β-galactosidase

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o Used to pretreat milk to reduce lactose content or can  Production of fructose from glucose
be taken when milk products are ingested by lactase o Glucose is reduced to sorbitol by aldose reductase,
deficient individuals which reduces the aldehyde group to an alcohol.
o Sorbitol is then reoxidized at carbon 2 by sorbitol
XIII. FRUCTOSE METABOLISM dehydrogenase to form fructose

B. Hexokinase Pathway
 In muscles, adipose tissues, kidneys
 Fructose metabolism in muscle differs little from
glycolysis
 Hexokinase has high Km, Low fructose affinity
 Less favored and much slower unless fructose
consumption is high

Step 1: Fructose -> Fructose 6-phosphate

 Enzyme: hexokinase
 Same hexokinase that phosphorylates glucose to
Glucose-6-Phosphate
 Fructose phosphorylated to Fructose-6-Phosphate in
entry to muscles cells with ATP as terminal phosphate
donor
 Only one reaction step prior to its entry to glycolysis
Therefore, it follows the rest of glycolytic steps

Step 2: Fructose-6-phosphate->Fructose 1,6- bisphosphate

 Enzyme: phosphofructokinase I
 Irreversible step of glycolysis

Step 3: F1,6P -> DHAP + GADP

 Enzyme: aldolase A

C. Fructokinase Pathway
The major dietary source of fructose is the disaccharide  Major pathway in the liver and small intestines
sucrose in table sugar and fruit, but it is also present as the  More favored pathway and major route for fructose
monosaccharide in corn syrup, which is used as a sweetener. phosphorylation
 6 enzymes to convert fructose to glycolytic Intermediates
 Conversion of fructose to glycolytic intermediates
o Fructose is metabolized mainly in the liver, where it is Step 1: Fructose -> Fructose 1-phosphate
converted to pyruvate or, under fasting conditions, to  Enzyme: fructokinase – present only in liver
glucose.  ATP as terminal phosphate donor
 Fructose is phosphorylated by adenosine
triphosphate (ATP) to form fructose 1-phosphate. Step 2: Fructose 1- phosphate -> Deglyceraldehyde +
The enzyme is fructokinase. DHAP
 Fructose 1-phosphate is cleaved by aldolase B to  Enzyme: aldolase B or fructose 1-phosphatase (aldolase
form dihydroxyacetone phosphate (DHAP) and only found in liver)
glyceraldehyde, which is phosphorylated by ATP to  Products: trioses
form glyceraldehyde 3-phosphate.
 Rate-limiting step
 DHAP and glyceraldehyde 3-phosphate are
intermediates of glycolysis.
Step 3: Glyceraldehyde -> Glyceraldehyde-3-phosphate
o In tissues other than liver, the major fate of fructose is
(GAP)
phosphorylation by hexokinase to form fructose 6-
 Enzyme: triokinase or glyceraldehyde kinase
phosphate, which enters glycolysis.
 Direct phosphorylation by ATP

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XIV. OTHER INFORMATION o More pyruvate (and acetyl CoA) is formed than is
required for ATP formation
 Fructose o Diet rich in fructose or sucrose leads to fatty liver
o From dietary sucrose like honey, fruits, corn syrup; because of overproduction of pyruvate, a
from hydrolysis of sucrose or table sugar precursor in synthesis of fats and cholesterol
o It may be acted upon by fructokinase in the liver (lipogenic effect of fructose)
o Enters pathway of intermediary metabolism via o Uncontrolled hyperglycemia
phosphorylation via hexokinase pathway and XV. POLYOL OR SORBITOL PATHWAY
fructokinase pathway OTHER I

 Production of Fructose 6-phosphate

 Diet, sucrose (catalyzed by fructokinase)  D-Fructose
 TAG & Phospholipid Synthesis
 Diet, sucrose (catalyze by fructokinase)  D-Fructose
(catalyzed by hexokinase, which is the unpreferred
route)  pyruvate NFORMATION
 Neither hexokinase nor phosphofructokinase can  Both fructose and sorbitol are found in the lens of the eye
phosphorylate fructose 1-phosphate at C6 to form the in increased concentrations in diabetes mellitus and may
glycolytic intermediate fructose 1,6-bisphosphate. It is the be involved in the pathogenesis of diabetic cataract
fructokinase enzyme that turns D-fructose into fructose-1-  The Polyol or Sorbitol pathway (not found in the liver) is
phospate. responsible for fructose formation from glucose and
 D fructose can be catalyzed by the Hexokinase enzyme increases in activity as glucose concentration rises in
in muscle, kidney, and adipose tissue. those tissues that are not insulin-sensitive—the lens,
o Becomes fructose-6-phosphate and is regulated by peripheral nerves, and renal glomeruli
phosphofructokinase 1(PFK1)  Glucose is reduced to sorbitol by aldose reductase,
 D-fructose from the diet can be acted upon by followed by oxidation of sorbitol to fructose in the
fructokinase in the liver (preferred route) presence of NAD+ and sorbitol dehydrogenase (polyol
o Can have preferential production of TAGS and dehydrogenase)
phospholipids.  Sorbitol does not diffuse through cell membranes but
 D-fructose from the diet may be acted upon by accumulates, causing osmotic damage. Simultaneously,
Hexokinase can produce pyruvate. myoinositol levels fall.
 D-fructose in the liver, which is acted upon your
fructokinase, does not go through your PFK1 anymore. XVI. DISORDERS OF FRUCTOSE METABOLISM
o Directly becomes fructose-1-phospate to become
DHAP. A. Enzyme Deficiencies
o Bypasses the regulatory steps o Increases risk of fatty  Essential Fructosuria
live disease x DHAP and GAP condense to form
o Rare, due to lack of hepatic fructokinase
fructose 1,6- bisphosphate that enters glycogenesis
o No toxic metabolites of fructose occurs in the liver,
pathway
hence benign asymptomatic or benign condiction.
 Glycerol 3-phosphate can enter TAG biosynthetic o Fructosemia and fructosuria develops in fructose
pathway consumption secondary to impaired fructose utilization
 Metabolism of 1 molecule of fructose to 2 molecules of o Some fructose is phosphorylated by hexokinase in
pyruvate yields 2 molecules of ATP and 2 molecules non-hepatic tissues; some appear in the urine
of NADH (same yield as conversion of glucose to
pyruvate)  Hereditary Fructose Intolerance
 Fate of fructose in parallel with glucose o Due to lack of aldolase B
 Effect of bypassing PFK-1 reaction: o Accumulation of fructose 1-PO2 in the liver, kidney
o Fructokinase pathway is the more favored damage and hypoglycemia from inhibition of
pathway and is the major route for fructose gluconeogenesis & glycogenolysis
phosphorylation. o Self-limiting; individuals rapidly develop a strong
o Conversion of fructose into the 2 trioses distaste for anything sweet
glyceraldehyde and DHAP is not regulated, therefore
fructose is more rapidly ‘glycolyzed’ or oxidized than B. Substrate Overproduction
glucose.
 Diet rich in fructose or glucose may lead to fatty liver
because of over production of pyruvate which is a

TRANSCRIBERS Guillermo, Hernandez, Inocencio, EDITORS De Jesus, Lim 11 of 12

Khow, Kierulf, La’O
 2.02 OXIDATION OF HEXOSES BIOCHEMISTRY 2020C

precursor in the synthesis of fats and cholesterol via

acetyl CoA

XVII. METABOLISM OF MANNOSE

 Minor diet component (dietary glycoproteins and certain

polysaccharides)
 Unimportant energy source
 C2 epimer of glucose (aldohexose)

A. Steps in Mannose Metabolism

Step 1: Mannose -> Mannose-6-Phosphate

 Enzyme: HEXOKINASE
 ATP as terminal phosphate donor

Step 2: Mannose-6-Phosphate -> Fructose-6-Phosphate

 Enzyme: PHOSPHOMANNOSE ISOMERASE
 Isomerization
 Fructose-6-Phosphate enters glycolytic pathway
 Produces the same metabolic products as glucose,
fructose, and galactose. (ATP, NADH2, CO2 and H2O)

Mannose via fructose-6-phosphate can also enter mainstream

of gluconeogenesis, glycogenesis, HMP and uronic acid
pathway

REFERENCES:
1. Harpers Illustrated Biochemistry 28th Edition
2. 2019 A, B, and C’s transes
3. Madarcos, Floro B., MD’s Powerpoint for Glycolysis

TRANSCRIBERS Guillermo, Hernandez, Inocencio, EDITORS De Jesus, Lim 12 of 12

Khow, Kierulf, La’O