CHAPTER 2: MAJOR METABOLIC PATHWAYS - …portal.unimap.edu.my/portal/page/portal30/Lecturer Notes...CHAPTER 2: MAJOR METABOLIC PATHWAYS ... Compounds (sugars, amino acids) ... Catabolism

CHAPTER 2:

MAJOR METABOLIC

PATHWAYS

ERT 317 BIOCHEMICAL ENGINEERING SEM 1 2012/13

Course details

Credit hours/Units : 4

Contact hours : 3 hr (L), 3 hr (P) and 1 hr (T) per week

Evaluations

Final Exam – 50%

Midterm Tests – 20%

Course works – 30%

Laboratories – 15%

Assignments – 15%

CARRY MARKS – 50%

Course details

Course Outcome (COs) will be covered:

CO2 – Ability to evaluate microbial system based on its

metabolic pathways and kinetics study in batch and

continuous cultures.

Course works

Assignments

Quizzes

Midterm test 1 – 22.10.2012 (Mon)

Class participations – Max. of 3 points

Important reminder

Attendance should not less than 80%, or else you will be barred from taking final examination.

Plagiarism and copying other students’ work is strictly prohibited especially in doing assignments and lab reports, or else both parties will get zero.

Cheating in quizzes and examinations is also prohibited, or else both parties will get zero.

Therefore, study hard and smart. Take note of the important chapters or things that will be highlighted throughout lectures.

Week 4-5 (01 - 12 Oct 2012)

Reading assignment:

1. Chapter 5, Bioprocess Engineering basic

Concepts. Shuler and Kargi (Main)

Major Metabolic Pathways C2

Introduction

Metabolism is the collection of enzyme catalyzed

reactions that convert substrates that are external to the

cell into various internal products.

Characteristics of Metabolisms

1. Varies from organisms to organism

2. Many common characteristics

3. Affected by environmental conditions

a) O2 availability: Saccharomyces cerevisiae

i. Aerobic growth on glucose → more yeast cells

ii. Anaerobic growth on glucose → ethanol

b) Control of metabolism is important in bioprocesses

ER 211/1 - Chapter 3

Types of Metabolism

Catabolism

Metabolic reactions in the cell that degrade a substrate

into smaller / simpler products.

Glucose → CO2

Anabolism

Metabolic reactions that result in the synthesis of larger

/ more complex molecules.

ERT 211/1 - Chapter 3

Figure 3.1: Classes of Reactions

Classification based on Metabolism

Where microbes get their energy?

Sunlight vs. Chemical

Photo- vs. Chemo- trophs

How do they obtain carbon?

Carbon Dioxide (or inorganic cmpds.) vs. Organic Compounds (sugars, amino acids)

Auto- vs. Hetero- trophs

Examples

Photoautotrophs vs. Photoheterotrophs

Chemoautotrophs vs. Chemoheterotrophs


Table 3.1:Types of -trophs

Type Energy C source Example

Photoauto- Sun CO2 Purple and green

sulfur bacteria

Photohetero- Sun Organic

compounds

Purple and green

non-sulfur bacteria

Chemoauto- Chemical

bonds

CO2 H, S, Fe, N bacteria

Chemohetero- Chemical

bonds

Organic Most bacteria,

fungi, protozoa,

animals


Bioenergetics

The source of energy to fuel cellular metabolsim is

“reduced” forms of carbon (sugars, hydrocarbons, etc.)

The Sun is the ultimate source via the process of

Photosynthesis in plants:

CO2 + H2O + hv → CH2O + O2


ATP - Adenosine Triphosphate

Catabolism of carbon-containing substrates

generates high energy biomolecules


Thermodynamic principles

Free-energy change ∆G’ of single chemical reaction:

αA+βB→γC+δD (3.1)

∆G’= ∆G°’ +RT ln (cγdδ/aαbβ) (3.2)

∆G°’ = -RT ln K’eq (3.3)

K’eq = (cγdδ/aαbβ) (3.4)


Example:

Consider a typical cell with [ATP] = 3.0 mM, [ADP] = 0.8 mM, and [Pi] = 4.0 mM. Free energy at 37°C.

Solution:

∆G’= ∆G°’ +RT ln ([ADP][Pi]/[ATP])

= -30.5 kJ/mol + (8.3145 J/Kmol)(310 K) ln (0.8 E-3 M x 4.0 E-3 M/3.0 E-3 M)

= -30.5 KJ/mol – 17.6 kJ/mol

=-48.1 kJ/mol


Metabolic Reaction Coupling: ATP

and Other Phosphate Compounds

Enzymatic hydrolysis of ATP yielding ADP and

inorganic phosphate (Pi) as well as releasing (-) large

free-energy and reversing the reaction with addition

of phosphate to ADP, free energy can be stored (+)

for later use.


Metabolic Reaction Coupling: ATP and

Other Phosphate Compounds


Metabolic Reaction Coupling: Oxidation and

reduction coupling via NAD

Recall

Oxidation = Loses electrons e.g dehydrogenation

Reduction = Addition electrons e.g hydrogenation

Example: Reduction of pyruvic acid and oxidation of lactic acid


Metabolic Reaction Coupling: Oxidation and

reduction coupling via NAD

Pairs of hydrogen atoms freed during oxidation or required in reduction are carried by nucleotide derivatives, NAD and phophorylated form NADP


NAD+ and NADP +

Nucleotide

derivatives

that accept

H+ and e

during

oxidation

/reduction

reactions


Thermodynamic Principle

Oxidation-reduction reaction:

Aox + Bred Aox + Bred

∆E°’= E°’(Aox/Ared) - E°’(Box/Bred) (3.5)

Standard half-cell potential

Aox + 2e → Ared (3.6)

The hydrogen half cell (pH=0)

2H + 2e → H2 E0 = 0.00 V (3.7)

Free-energy:

∆G°’ = -n F ∆E’ (3.8)


Carbon Catabolism

Embden- Meyerhof-Parnas (EMP) Pathway

Pentose Phosphate Pathway

Entner Doudoroff (ED) Pathway

Overview of Glucose Metabolism

• Under aerobic conditions glucose is converted to pyruvate by glycolysis while generating two ATPs

• Under aerobic conditions, pyruvate is further oxidized by the citric acid cycle and oxidative phosphorylation to generate CO2 and H2O

• Under anaerobic conditions, pyruvate is instead converted to a reduced end product, that is,

In muscle: lactate - homolactic fermentation

In yeast: ethanol + CO2 - alcoholic fermentation

(note: fermentation is an anaerobic biological reaction process)


Glucose

Metabolism


Glycolysis

• Glycolysis is the breakdown (catabolism) of glucose to pyruvate under aerobic conditions

To understand the pathway at 4 levels:

1. The chemical interconversion steps or the sequence of reactions by which glucose is converted to the pathway end’s product , i.e., pyruvate

2. The mechanism of the enzymatic conversion of each pathway intermediates and its successor

3. The energetics of the conversion, ∆G and ∆

4. The mechanisms controlling the flux (rate of flow) of metabolites through the pathway

• Glycolysis converts C6 glucose to two C3 pyruvate

• The free energy released in this process is harvested to synthesise ATP from ADP and Pi

• They are 10 reactions involved in the glycolysis, all catalaysed by 10 specific enzymes

• The enzymes of glycolysis are located in the cytosol where they are only loosely

associated

Glycolysis can be divided into two stages:

Stage 1:

Energy investment

Reactions 1-5 of the pathway are involved

Hexose (C6)glucose is phosphorylated and cleaved to yield 2 molecules of triose

(C3) glyceraldehydes -3-phosphate (GAP)

The process consumes 2 ATPs

Stage 2:

Energy recovery

Reactions 6-10 of the pathway are involved

The two molecules of GAP are converted to pyruvate

The process generates 4 ATPs

Glycolysis


Slide 6

The reactions of glycolysis


• There are 10 reactions catalyzed by 10 different enzymes

1. Hexokinase: First ATP Utilization

2. Phosphoglucose Isomerase

3. Phosphofructokinase: Second ATP Utilization

4. Aldolase

5. Triose Phosphate Isomerase

6. Glyceraldehyde-3-Phosphate Dehydrogenase: First “High Energy” Intermediate Formation

7. Phosphoglycerate Kinase: First ATP Generation

8. Phosphoglycerate Mutase

9. Enolase: Second “High energy” Intermediate Formation

10. Pyruvate Kinase: Second ATP Generation

Glycolysis: Reaction 1

• The reaction is the conversion of

glucose to form glucose-6-phosphate

(G6P)

• First ATP Utilization

• The reaction involves the transfer of a

phosphoryl group from ATP to glucose

to form glucose-6-phosphate (G6P)

• The reaction is catalyzed by

hexokinase (HK)

• The reaction needs Mg2+ ion

• Uncomplex ATP is inhibitory

Note: Kinase enzyme catalyzes the transfer of

phosphoryl groups between ATP and other

molecules


Why is Mg2+ required in any kinase enzyme activity?

Mg2+ complexed with ATP at the phosphate oxygen atoms

This shield their negative charges, making the γ-phosphorous atom of ATP more

accessible for the nucleophilic attack by the C6-OH group of glucose

Other divalent ions which can replace Mg2+ is Mn2+

α β γ 1

2 3

4

5

6




glucose-6-phosphate (G6P) to form

fructose-6-phosphate (F6P)


phosphoglucose isomerase (PGI)

• This reaction is the isomerization of

an aldose to a ketose

• The proposed mechanism for the PGI

reaction involves the general acid-

base catalysis by the enzyme

• Involves ring opening and ring

closure between C1 and O

aldose

ketose



• The reaction is the conversion of fructose-6-phosphate

(F6P) to form fructose-1,6-bisphosphate (FBP)

• The reaction is catalyzed by phosphofructokinase (PFK)

• Second ATP Utilization

• Reaction is similar to hexokinase

reaction, catalyzing the nucleophilic attack by C1-OH

group of F6P on the electrophilic γ-phosphorous atom of

Mg2+-ATP complex

• PFK catalyzes one of the pathway’s rate-determining

reaction, it function with large negative free energy

changes

• One of the 3 non-equilibrium rxn in glycolysis (others

are HK and PK)

Mechanisms that control PFK activity:

ATP is both a substrate and also an allosteric inhibitor of

enzyme

ADP, AMP reverse the inhibitory effect of enzyme,

therefore they are activators



• The reaction is the cleavage of fructose-1,6-

bisphosphate (FBP) to form the two trioses,

glyceraldehyde -3-phosphate (GAP) and

dihydroxyacetone phosphate (DHAP)

• Bisphosphate, not diphosphate as the

phosphoryl gp are not linked

• The reaction is catalyzed by aldolase

• This reaction is an aldol cleavage between

C3 and C4 which requires carbonyl at C2

and hydroxyl at C4

• The two trioses are interconvertible and thus

can enter a common degradative path

• Each trioses has a phosphoryl gp

• Carbon atoms of 1, 2 and 3 of glucose

become atom 3, 2 and 1 of DHAP and 4, 5

and 6 of glucose become 1, 2 and 3 of

GAP


Mechanism for base-catalysed aldol cleavage

The presence of enolate intermediates



• Reaction 4 results in the

production of glyceraldehyde -3-

phosphate (GAP) and

dihydroxyacetone phosphate

(DHAP), which are ketose-aldose

isomers

• Only GAP will continue to be

degraded in the glycolysis

• Reaction 5 is the interconversion

of GAP to DHAP, occurs via an

enediol or enediolate

intermediate

• This reaction is catalyzed by

triose phosphate isomerase

(TIM) ERT 211/1 - Chapter 3


• Involves the oxidation and

phosphorylation of glyceraldehyde -3-

phosphate (GAP) by NAD+ and Pi to

form 1,3-bisphosphoglycerate (1,3-BPG)


glyceraldehyde-3-phosphate

dehydrogenase

• The reaction is very exergonic and this

drives the synthesis of “high energy”

compound, 1,3-BPG

• 1,3-BPG is one of the phosphate

compounds with high standard free

energy, higher than ATP


Slide 15


Table 3.2: Standard Free Energies of Phosphate Hydrolysis of some biological

compound


• The reaction is the conversion of 1,3

bisphosphoglycerate (1,3-BPG)

to form 3-phosphoglycerate (3PG)


phosphoglycerate kinase (PGK)

• The reaction results in a generation

of its first ATP molecules in the

presence of ADP and Mg2+


Mechanism of phosphoglycerate kinase (PGK) reaction




3-phosphoglycerate (3PG) to

form 2-phosphoglycerate (2-PG)


phosphoglycerate mutase

(PGM)

• Note: a mutase catalyzes the

transfer of a functional group

from one position to the another

on a molecule

• The reaction is a necessary

preparation for the next reaction

which generates a “high energy”

phosphoryl compound for use in

the ATP synthesis


Proposed reaction mechanism for phosphoglycerate mutase (PGM)

•The active form of the enzyme

contains Phos-His residue at the

active site

Step 1: 3-PG binds to PGM in

which His is phosphorylated

Step 2: The phosphoryl gp is

transferred to the substrate,

resulting in an intermediate 2,3-

PG.enzyme complex

Steps 3 and 4: The complex

decomposes to form 2-PG with

regeneration of the

phosphoenzyme

•Occasionally, 2,3-BPG

dissociates from enzyme leaving

an inactive dephosphoenzyme

like in Step 5



• The reaction is the conversion

of 2-phosphoglycerate (2-

PG) to phosphoenolpyruvate

(PEP)

• This reaction is catalyzed by

enolase

• The reaction generate a

second “High energy”

intermediate compound, PEP

(refer to Table 13-2)


Remember

Table 13-2, Page 362-Standard Free Energies of Phosphate Hydrolysis of some

biological cpds



• The final reaction in glycolysis is the

conversion of phosphoenolpyruvate

(PEP) to form pyruvate

• The reaction is catalyzed by pyruvate

kinase (PK)

• One of the 3 non-equilibrium rxn in

glycolysis (others are HK and PFK)

• This reaction involves the coupling of

PEP hydrolysis to pyruvate to the

synthesis of ATP from ADP

• Thus the reaction generates the second

ATP molecules


Mechanism of the Reaction Catalyzed by

Pyruvate Kinase (PK) • Reaction requires both monovalent (K+) and divalent ions (Mg+)

Step 1: Nucleophilic attack of phosphorus atom of PEP by β-phosphoryl oxygen of ADP, thus displacing enolpyruvate and forming ATP; the reaction is endergonic

Step 2: Enolpyruvate converts to pyruvate, and this is a very exergonic reaction

• Overall reaction of PEP to pyruvate is exergonic


Summary on Glycolysis

• The overall reaction of glycolysis is:

Glucose + 2NAD+ + 2ADP + Pi → 2NADH + 2Pyruvate + 2ATP + 2H2O + 4H+

• The reaction occurs in 10 enzymatically catalysed reactions

• The mechanisms of the 10 glycolytic enzymes have been elucidated through chemical and kinetic measurements combined with X-ray structural studies

• 3 of the 10 reactions are non-equilibrium, which ensure the pathway go forward:

Reaction 1: Glucose to G6P by HK

Reaction 3: F6P to FBP by PFK

Reaction 10: PEP to pyruvate by PK


The Three Products of Glycolysis

1. ATP

2. NADH

3. PYRUVATE

1. ATP

• 2 ATP per molecule of glucose were invested and subsequently 4ATP were generated by substrate-level phosphorylation, giving a net yield of 2ATP per glucose

• ATP produced satisfies most of the cell’s energy needs.

2. NADH

• 2 NAD+ are reduced to 2 NADH

• Reduced NADH represent a source of free energy that can be recovered by subsequent oxidation

• Under aerobic condition, electron pass from reduced coenzymes thru’ a series of electron carriers to the final oxidizing agent, O2, in a process known as electron transport

• The free energy of electron transport drives the synthesis of ATP from ADP

• In aerobic organism, the sequence of events also serves to regenerate oxidized NAD+

• Under anaerobic conditions, NADH must be reoxidized by other means in order to keep the glycolytic pathway supplied with NAD+


The Three Products of Glycolysis (cont…)

3. PYRUVATE

• 2 pyruvate molecules are produced

• Under aerobic condition, complete oxidation of

pyruvate to CO2 and H2O via citric acid cycle and

oxidative phosphorylation, where ATP is generated

• In anaerobic metabolism, pyruvate is metabolized to

a lesser extent to regenerate NAD+, via a process

known as fermentation


THE PENTOSE PHOSPHATE PATHWAY

•Why the Pentose Phosphate Pathway (The PPP)

An alternative mode of glucose oxidation where G6P is converted to R5P or

hexoses to pentoses, and R5P and its derivatives are required for the synthesis of

RNA, DNA, etc.

The production of NADPH

•Tissues most heavily involved in lipid biosynthesis (liver, mammary gland, adipose tissue

and adrenal cortex) are rich in the PPP enzymes

•About 30% of the glucose oxidation in liver occurs via the PPP


THE PENTOSE PHOSPHATE PATHWAY (continue…)

•NADH vs NADPH

They are not metabolically interchangeable

NADH uses the free energy of metabolite oxidation to synthesise ATP (oxidative

phosphorylation), whereas NADPH uses the free energy of metabolite oxidation for

reductive biosynthesis (eg. biosynthesis of fatty acid and cholesterol require NADPH in

addition to ATP)

This differentiations is possible because the dehydrogenases involved in oxidative

and reductive metabolism are highly specific for their respective coenzymes, NADH or

NADPH


Nicotinamide nucleotides in catabolism and biosynthesis

• NAD+ is the cofactor for most enzymes that act in the direction of substrate oxidation

(dehydrogenases) whereas NADPH usually functions as a cofactor for reductases,

enzymes that catalyze substrate reduction

• NADPH is synthesized either from NADP+ in the PPP or from NADH through the action

of mitochondrial energy-linked transhydrogenase

• NADP+ is synthesized from NAD+ by an ATP-dependent kinase reaction



Overall rxn:

3 G6P + 6 NADP+ + 3 H2O 6 NADPH + 6 H+ + 3 CO2 + 2 F6P + GAP

Occurs in 3 stages:

Stage 1: Oxidative rxn (Rxn 1-3) which yield NADPH and ribulose-5-phosphate (Ru5P)

3 G6P + 6 NADP+ + 3 H2O 6 NADPH + 6 H+ + 3 CO2 + 3 Ru5P

G6P generated from hexokinase on glucose (glycolysis) or glycogen breakdown

Only Rxn 1-3 of pathway are involved in the production of NADPH

2 molecules of NADPH are generated per 1 molecule of G6P that enter pathway

Stage 2: Isomerization and epimerization rxn (Rxn 4 and 5) which transform Ru5P either

to ribose-5-phosphate (R5P) or xylose-5-phosphate (Xu5P)

3 Ru5P R5P + 2 Xu5P



Stage 3: A series of C-C bond cleavage and formation rxn (Rxn 6-8) that convert 2

molecules of Xu5P and one molecule of R5P to 2 molecules of F6P and one molecule of

GAP

transketolase

transaldolase

transketolase

2 Xu5P + 1 R5P 2 F6P 1 GAP



1. Gluco-6-phosphate

dehydrogenase (G6PD)

2. 6-phospho-glucono-

lactonase

3. 6-phospho-gluconate

dehydrogenase

4. Ribulose-5-phosphate

isomerase

5. Ribulose-5-phosphate

epimerase

6. Transketolase

7. Transaldolase

8. Transketolase

Note: Epimers are sugars that

differ only by the

configuration at one carbon

atom



Relationship between

Glycolysis and The Pentose

Phosphate Pathway

•The PPP starts with G6P produces

in Step 2 of Glycolysis

•It generates NADPH for use in

reductive biosynthesis and R5P for

nucleotide biosynthesis

•Excess R5P is converted to

glycolytic intermediates by a

sequence of reactions that can

operate in reverse to generate

additional R5P, if needed


Entner Doudoroff (ED) Pathway

Overall stoichiometry of the reaction:

Glucose + ATP + NADP + → glyceralde 3-phosphate +

pyruvic acid + ADP + NADPH + H+

2 moles of ADP were phosphorylated by reacting one

mole of GA-3P to pyruvate through the same reaction

as used for this conversion in EMP pathway

Energy yield: onemole of ATP per mole glucose

processed


Summary of Carbon Catabolism

3 Glucose molecules enter glycolysis (EMP pathway), produce 6

ATP

3 Glucose molecules through the Pentose Phosphate Pathway and

then reenter glycolysis, produce 5 ATP

3 Glucose molecules enter ED pathway, produce 3 ATP


FERMENTATION

1. Homolactic Fermentation

•In muscle, under anaerobic condition e.g., during vigorous activity when the demand for ATP is

high and O2 is in short supply:

NADH is oxidised by pyruvate to generate NAD+ and lactate by lactate dehydrogenase

(LDH)

The reaction is reversible, so pyruvate and lactate level are readily equilibrated

The reaction is also known as anaerobic glycolysis, the stage where the conversion of

pyruvate to lactate is classified as Reaction 11

The overall process of an anaerobic glycolysis in muscle can be represented as:

Glucose + 2 ADP + 2Pi 2 Lactate + 2 ATP

The lactate may be:

exported out of the cell by blood to the liver where it is used to synthesise glucose, or

converted back to pyruvate, to enter the pathway for further degradation


1. Homolactic Fermentation (continue…)


FERMENTATION (continue..)

2. Alcoholic Fermentation

• In yeast, under anaerobic condition, pyruvate is converted to ethanol and CO2 while

regenerating NAD+

• Yeast produces ethanol and CO2 via 2 consecutive reactions:

The carboxylation of pyruvate to form acetaldehyde and CO2 as catalyzed by

pyruvate decarboxylase (enzyme not present in animals), then

The reduction of acetaldehyde to ethanol by NADH as catalysed by alcohol

dehydrogenase, thereby generating NAD+


Alcoholic Fermentation (continue…..)

The two reactions of alcoholic fermentation:

Thiamin

diphosphate

(TPP)-essential

cofactor of

pyruvate

decarboylase

1. Pyruvate

decarboxylase

2. Alcohol

dehydrogenase


Fermentation (continue..)

The Energetics of Fermentation

•Overall Reaction in alcoholic fermentation (from glucose)

Glucose + 2Pi +2ADP 2 Ethanol + 2CO2 + 2ATP ∆G = -196 kJ.mol-1

•Overall Reaction in homolactic fermentation (from glucose)

Glucose + 2Pi +2ADP 2 Lactate + 2ATP ∆G = -235 kJ.mol-1

•Each of these processes is coupled to the net formation of 2ATP molecules


Fermentation (continue..)

The Energetics of Fermentation (continue…)

•They are non-oxidative process

•No net oxidation and reduction

•NAD+ and NADH do not appear in the overall net reaction

•NADH formed in the oxidation of GAP is consumed in the reduction of pyruvate

•The regeneration of NAD+ in the reduction of pyruvate to lactate or ethanol sustains the

continued operation of glycolysis under anaerobic conditions

•Only a small fraction of the energy of glucose is released in the anaerobic conversion to

lactate or ethanol (2ATP per glucose vs. 38ATP per glucose in ox. phos.)

•The rate of ATP production is higher in anaerobic than in aerobic glycolysis

•Much more energy can be extracted aerobically via citric acid cycle and oxidative

phosphorylation step


METABOLISM OF OTHER HEXOSES

• Three other hexoses apart

from glucose are:

1. Fructose

2. Galactose

3. Mannose

• After digestion monosaccharides

enter the blood stream, which

carries them to various tissues

• Fructose, galactose and mannose

are converted to glycolytic

intermediates then metabolized

in the glycolytic pathway


METABOLISM OF OTHER HEXOSES (continue..)

1. Fructose

• From fruits and sucrose (a disaccharides of fructose and glucose)

• 2 pathways for the metabolism of sucrose because of the presence of different enzymes

in different tissues

• In muscle, fructose converts to F6P which then enter the glycolytic pathway. This only

require 1 step, thus 1 enzyme,HK

• In liver, fructose converts to intermediates and finally GAP which then enter the

glycolytic pathway. This require 7 steps thus 7 enzymes


METABOLISM OF OTHER HEXOSES (continue…)

Metabolism of

fructose

1. fructokinase

2. 2 Fructose-1-

phosphate

aldolase

3. Glyceraldehyde

kinase

4. Alcohol

dehydrogenase

5. Glycerol kinase

6. Glycerol

phosphate

dehydrogenase

7. Triose phosphate

isomerase

METABOLISM OF OTHER HEXOSES (continue..)

1. Fructose (continue…)

•In muscle, after Rxn 4, there are 2 pathway leading from glyceraldehyde to GAP, before

entering the pathway, both consume ATP

•NADH is oxidized in in Rxn 4 but is being reduced again in Rxn 6

•What happens when there is an excessive fructose in blood, eg. In IV feeds?

•Fructose intolerance-a genetic diseases with deficiency in Fructose-1-phosphate aldolase

Fructose-1-phosphate may be produced faster than aldolase can cleave,

accumulation of fructose-1-phosphate depletes Pi in liver, ATP drops, glycolysis and

production of lactate is activated, high concentration of lactate in blood is deadly


Metabolism of other HEXOSES (continue..)

2. Galactose

•Obtained from the hydrolysis of lactose from dairy products

•Lactose is disaccharide of galactose and glucose

•Hexokinase only recognise glucose, fructose and mannose but not galactose

•Epimerization rxn must occur before galactose enter glycolysis

•Galactose is converted to G6P which then enter the glycolytic pathway. This require 4 steps

and 4 enzymes



Metabolism of

galactose

1. Galactokinase

2. Galactose-1-

phosphate uridyl

transferase

3. UDP-galactose-4-

epimerase

4. phosphoglucomutase



2. Galactose (continue…)

•Galactosemia- a genetic disease characterized by the inability to convert galactose to

glucose

•Involve the deficiency of enzyme of Rxn 2

•Symptoms:

Failure to grow well

Mental retardation

Death from liver damage

•Treatment- galactose free diet



3. Mannose

•A product of digestion of polysaccharides and glycoprotein

•A C2 epimer of glucose (Epimer is sugars that differ only by the configuration at one C

atom)

•Mannose enter the glycolytic pathway after its conversion to F6P. It need 2 steps thus 2

enzymes



Metabolism of mannose

1. hexokinase

2. Phosphomannose isomerase


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CHAPTER 2: MAJOR METABOLIC PATHWAYS - …portal.unimap.edu.my/portal/page/portal30/Lecturer Notes...CHAPTER 2: MAJOR METABOLIC PATHWAYS ... Compounds (sugars, amino acids) ... Catabolism