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CARBOHYDRATE METABOLISM Lecture Notes 2022

Carbohydrates are a large group of compounds that serve many functions in organisms. They can be divided into monosaccharides, disaccharides, oligosaccharides, and polysaccharides depending on their size. Glycolysis is the major pathway for glucose breakdown that occurs in the cytosol of cells. It involves a series of enzyme-catalyzed reactions that splits glucose into two pyruvate molecules, generating a small amount of ATP in the process.

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0% found this document useful (0 votes)
37 views20 pages

CARBOHYDRATE METABOLISM Lecture Notes 2022

Carbohydrates are a large group of compounds that serve many functions in organisms. They can be divided into monosaccharides, disaccharides, oligosaccharides, and polysaccharides depending on their size. Glycolysis is the major pathway for glucose breakdown that occurs in the cytosol of cells. It involves a series of enzyme-catalyzed reactions that splits glucose into two pyruvate molecules, generating a small amount of ATP in the process.

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202210034
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© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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What are Carbohydrates?

• The term carbohydrates refer to a very large


group of compounds that are:
CARBOHYDRATE METABOLISM
– Hydrated carbons with the general formula
Cn(H2O)m

– Polyhydroxy aldehydes, polyhydroxy ketones or


the compounds that yield these compounds after
Nigani Willie (MSc, BSc ) hydrolysis
Discipline of Biochemistry And Molecular Biology
Division of Basic Medical Sciences
School of Medicine And Health Sciences
University of Papua New Guinea
Taurama Campus

Hydroxyl Aldehyde Ketone


Some General Facts
• Most abundant organic compounds in the
plant world
• Most abundant biomolecules on Earth
D-Glucose D-Fructose α-D-Glucose
(α-D-Glucopyranose) • Certain carbohydrates (sugar and starch) are a
dietary staple in most parts of the world
• Oxidation of carbohydrates is the central
energy-yielding pathway in most non-
photosynthetic organisms

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Uses of Carbohydrates in Organisms Uses of Carbohydrates in Organisms


• substrate for energy in most organisms • participate in recognition and adhesion
between cells
• Insoluble carbohydrate polymers serve as
structural and protective elements • more complex carbohydrate polymers
– in the cell membranes and cell walls covalently attached to proteins or lipids act as
– in connective tissues of animals signals that determine the intracellular
location or metabolic fate of these molecules
• Lubrication (synovial fluid) for skeletal joints
• components of nucleotides and nucleic acids
(DNA and RNA)

Carbohydrates classification Monosaccharide Disaccharide Oligosaccharides Polysaccharides

• simple sugars
Carbohydrates can be divided into four major • consist of a single • Consists of two • Short chains of 2 – • Consists of more
polyhydroxy monosaccharides 10 than 10
classes: aldehyde or monosaccharide monosaccharide
polyhydroxy units unites
1) Monosaccharides ketone
• carbohydrate that • Can be hydrolyzed • Will yield 2 – 10 • Will yield more
cannot be into two monosaccharides than 10
2) Disaccharides hydrolyzed any monosaccharides when completely monosaccharides
further hydrolyzed when completely
hydrolysed
3) Oligosaccharides • Eg. glucose, • Eg. Lactose, • Eg. Raffinose
galactose, fructose sucrose, maltose • Eg. Amylose,
4) Polysaccharides amylopect,
glycogen,
cellulose,

The word “saccharide” is derived from the Greek


word sakcharon, meaning “sugar”

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Amylose
amylose

Amylopectin α-1,6 Glycosidic bond α-1,4 Glycosidic bond


amylopectin
glycogen

CARBOHYDRATE METABOLISM GLYCOLYSIS


• Glycolysis, the major pathway for glucose, occurs
in the cytosol of cells
• From the Greek word glykys, meaning “sweet”
and lysis, meaning “splitting”
• In glycolysis, one molecule of glucose (a 6-carbon
GLUCOSE compound) is split into two molecules of
pyruvate (a 3-carbon compound)
Glycolysis
• Glycolysis, like most other metabolic pathways,
involves a series of enzyme-catalysed reactions
PYRUVATE

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Preparatory Phase
• The first five steps of glycolysis
• glucose is phosphorylated at the expense
• The breakdown of glucose via glycolysis is the of two ATP molecules
• glyceraldehyde 3-phosphate (and
sole source of metabolic energy for many dihydroxyacetone phosphate) are
generated
animal tissues and cell types (e.g. RBCs, renal • dihydroxy acetone can be converted to
glyceraldehyde 3-phosphate by triose
medulla, brain and sperm) phosphate isomerase

• The glycolysis pathway may be divided into two


phases: The Payoff Phase
• final five steps of glycolysis

1. Preparatory Phase • glyceraldehyde 3-phosphate is


converted to pyruvate
• 2 ATP molecules and NADH are
2. Payoff Phase generated for every glyceraldehyde 3-
phosphate that is converted to
pyruvate
• Thus 4 ATP molecules are synthesised
in the payoff phase, i.e. net yield of 2
ATP molecules in glycolysis

arsenate

Phosphoglycerate kinase
1-arseno-3-phosphoglycerate

3-Phosphoglycerate + HEAT

• Enolase is inhibited by fluoride.


• To prevent glycolysis in the
estimation of glucose, blood is
collected in tubes containing
fluoride.

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Glycolysis Summary: Fates of Pyruvate:

Pyruvate
1 Glucose
2 ATP

2 ADP

2 Glyceraldehyde 3-phosphate
4 ADP 2 NAD+

+ 4 ATP 2 NADH

2 Pyruvate

Fates of Pyruvate: Fates of Pyruvate:

Pyruvate Pyruvate
NAD+ NAD+ NADH
Pyruvate Pyruvate
dehydrogenase dehydrogenase Lactate
complex complex dehydrogenase

NADH NADH NAD+

Acetyl-CoA Acetyl-CoA Lactate

Kreb’s Cycle Kreb’s Cycle

AEROBIC CONDITIONS AEROBIC CONDITIONS ANAEROBIC CONDITIONS

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Fates of Pyruvate:
Glucose Entry into Cells/Tissues
Pyruvate Tissue Location Function
NAD+ NADH Pyruvate Facilitative bidirectional transporters
Pyruvate
Lactate Brain, kidney, colon, placenta,
dehydrogenase
dehydrogenase GLUT 1 Uptake of glucose
complex Pyruvate erythrocyte
decarboxylase
NADH NAD+ Liver, pancreatic B cell, small
GLUT 2 Rapid uptake and release of glucose
intestine, kidney
Acetyl-CoA Lactate Acetaldehyde
GLUT 3 Brain, kidney, placenta Uptake of glucose
Heart and skeletal muscle,
GLUT 4 Insulin-stimulated uptake of glucose
adipose tissue
Alcohol
dehydrogenase GLUT 5 Small intestine Absorption of glucose

Kreb’s Cycle Ethanol Sodium-dependent unidirectional transporter


+
Active uptake of glucose from lumen of
CO2 intestine and reabsorption of glucose
SGLT 1 Small intestine and kidney
in proximal tubule of kidney against a
in yeast
AEROBIC CONDITIONS ANAEROBIC CONDITIONS concentration gradient

Glucose metabolism in Erythrocytes Glucose metabolism in Erythrocytes


Glucose
• Glucose Transporter 1 • Glycolysis metabolism
Glucose
(GLUT1) transports glucose in RBCs also produces
through plasma an intermediate called
membrane into the 2,3-biphosphoglycerate
erythrocyte cytosol (2,3BPG) 2,3 BPG
Pyruvate
• Since RBCs lack Pyruvate 2,3 BPG • The interaction of
mitochondria glycolysis in 2,3BPG with the Hemoglobin

RBCs is anaerobic haemoglobin in RBCs


1

2

• Thus the end product of regulates O2-binding to


glycolysis in RBCs is lactic haemoglobin and Lactate 2,3-BPG

acid (lactate) Lactate oxygen release in the


tissues 2 1

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Brain Cells Muscles/Heart Cells

• use GLUT4 to transport glucose into cytosol


• use GLUT3 (does not require insulin) to
transport glucose into cytosol • GLUT4 is insulin-dependent

• Glycolysis yields pyruvate which is • Glycolysis yields pyruvate which is


subsequently oxidised to H20 and CO2 subsequently oxidised to H20 and CO2

• The pentose phosphate pathway is active; • Glycogenesis also occurs in these cells;
produces NADPH needed for reduction significant quantities of glycogen are made
reactions which are stored for later use

Adipocytes (Fat Cells) Live Cells


• also use GLUT4 (requires insulin)
• also use GLUT2 (does not require insulin)
• Glycolysis yields pyruvate which is oxidised by
pyruvate complex to acetyl-CoA
• Greatest number of uses for glucose
• acetyl-CoA is primarily used for fatty acid
synthesis
• In addition glycolysis, liver cells also use
• Glycolysis also provides glycerol 3-phosphate; glucose in Glycogenesis, Pentose Phosphate
required for TAG synthesis Pathway (Hexose Monophosphate Shunt) and
Uronic Acid pathway
• Adipocytes also carry out glycogenesis and
glycogenolysis

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Significance of Glycolysis CARBOHYDRATE METABOLISM


• Generation of ATP and NADH can occur
under anaerobic conditions and in cells that GLYCOGEN
lack mitochondria (e.g. RBCs)
Glycogenesis
• Formation of pyruvate from glucose sets the
stage for complete oxidation to CO2 and H2O
(in mitochondria) under aerobic conditions or GLUCOSE
for fatty acid synthesis
Glycolysis
• Production of 2,3-biphosphoglycerate (2,3-
BPG), vital component of erythrocytes, PYRUVATE
regulates haemoglobin affinity for 02

GLYCOGENESIS Glycogen Structure


• Glycogen synthesis, glycogenesis, occurs
mainly in the liver but due to its greater mass,
muscle contains more glycogen

• Muscle glycogen is a readily available source


of glucose for glycolysis within the muscle
itself; • Glycogen is a branched polymer of α-D-glucose
• The glucose residues are linked by an α-1,4-glycosidic bond
• Liver glycogen functions to store and export • Every tenth or so glucose residue has an additional α-1,6
glucose to maintain blood glucose between bond to another glucose
meals • These branches are extended by additional α-1,4-linked
glucose residues

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GLYCOGEN

GLYCOGENESIS
UTP
Branching
enzyme
Glycogen
synthase

Glycogen primer
UDP-Glucose
2Pi PPi

Glycogenin
• The pre-existing glycogen molecule, or “glycogen primer,” is UDP-glucose
pyrophosphorylase

necessary to initiate glycogenesis


Glucose 1-phosphate UTP
• The glycogen primer may be formed from another primer phosphoglumutase
known as glycogenin Glucose 6-phosphate
• Glycogenin is a protein that is glycosylated on a specific Mg2+ hexokinase/
glucokinase

tyrosine residue with a UDP-glucose GLUCOSE

GLYCOGEN GLUCAGON GLYCOGEN


EPINEPHRINE

UTP UTP
Branching Branching
enzyme enzyme
Glycogen Glycogen
cAMP synthase
cAMP synthase

Glycogen primer Glycogen primer


UDP-Glucose UDP-Glucose
2Pi PPi 2Pi PPi

UDP-glucose Glycogenin UDP-glucose Glycogenin


pyrophosphorylase pyrophosphorylase

Glucose 1-phosphate UTP Glucose 1-phosphate UTP


phosphoglumutase phosphoglumutase

Glucose 6-phosphate Glucose 6-phosphate


Mg2+ hexokinase/ Mg2+ hexokinase/
glucokinase glucokinase

GLUCOSE GLUCOSE

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INSULIN GLYCOGEN
CARBOHYDRATE METABOLISM

UTP

Glycogen
Branching
enzyme GLYCOGEN
cAMP synthase

UDP-Glucose
Glycogen primer Glycogenolysis Glycogenesis
2Pi PPi

UDP-glucose
pyrophosphorylase
Glycogenin GLUCOSE

Glucose 1-phosphate UTP


Glycolysis
phosphoglumutase

Glucose 6-phosphate
Mg2+ hexokinase/
glucokinase
PYRUVATE
GLUCOSE

GLYCOGENOLYSIS
GLYCOGENOLYSIS GLYCOGEN
Pi

• Glycogenolysis is the degradation of glycogen


to glucose Glucose 1-phosphate

phosphoglumutase

Glucose 6-phosphate
• Glycogenolysis is a separate pathway, NOT a
Glucose 6-
reverse of glycogenesis phosphatase

GLUCOSE

• Glycogen is readily available source of glucose

*Glucose-6-phosphatase is absent from brain and muscle cells

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GLYCOGENOLYSIS GLYCOGENOLYSIS
GLYCOGEN GLYCOGEN
Pi Pi

Glucose 1-phosphate Glucose 1-phosphate

phosphoglumutase cAMP phosphoglumutase cAMP

Glucose 6-phosphate Glucose 6-phosphate

Glucose 6- Glucose 6-
phosphatase phosphatase INSULIN

GLUCOSE GLUCOSE
GLUCAGON GLUCAGON

EPINEPHRINE EPINEPHRINE

*Glucose-6-phosphatase is absent from brain and muscle cells *Glucose-6-phosphatase is absent from brain and muscle cells

Clinical Aspects Glycogenosis Name Cause of Disorder Characteristics


Type I Von Gierke’s disease Deficiency of Glycogen overload in renal
glucose-6- tubule cells and hepatocytes;
• Glycogen storage disease (glycogenoses) phosphatase Hypoglycemia, lacticacidemia,
refers to a group of inherited disorders ketosis, hyperlipemia

characterized by deposition of an abnormal Type II Pompe’s disease Deficiency of Fatal, accumulation of glycogen
lysosomal α-1-4- in lysosomes, heart failure.
type or quantity of glycogen in the tissues glucosidase
and 1-6-
glucosidase
• Some recently discovered deficiencies are of
Adenylyl kinase and cAMP-dependent Type III Limit dextrinosis,
Forbes’ or Cori’s
Absence of
debranching
Accumulation of a characteristic
branched polysaccharide
protein kinase disease enzyme

Type IV Amylopectinosis, Absence of Accumulation of polysaccharide


• Some of the conditions described have Andersen’s disease branching
enzyme
having few branch points; Death
due to cardiac or liver failure in
benefited from liver transplantation first year of life

From Harper’s Biochemistry 1996

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Glycogenosis Name Cause of Disorder Characteristics


Type V Myophosphorylase Absence of muscle Diminished exercise tolerance;
GLUCONEOGENESIS
deficiency, phosphorylase muscles have abnormally high
glycogen content (2.5–4.1%);
Little or no lactate in blood
after exercise
• The formation of glucose from non-hexose
precursors is called gluconeogenesis
Type VI Hers’ disease Deficiency of liver
phosphorylase
High glycogen content in liver,
tendency toward hypoglycemia
(“formation of new sugar”)

Type VII Tarui’s disease Deficiency of As for type V but also


phosphofructokinase possibility of hemolytic anemia • Gluconeogenesis occurs in all organisms and is
in muscles and
erythrocytes
essential for survival as glucose levels have to
be maintained to support metabolism of
Type VIII Deficiency of liver
phosphorylase kinase
As for type VI. tissues/cells that use glucose as their primary
substrate

From Harper’s Biochemistry 1996

Glucose

hexokinase

Gluconeogenesis Glucose 6-phospate

Fructose 6-phospate
• In humans, gluconeogenesis enables the Phosphofructokinase-1

maintenance of blood glucose levels long Fructose 1, 6-phospate

after all dietary glucose has been absorbed Dihydroxyacetone phosphate Glyceraldehyde 3-phosphate
and completely oxidized and glucose stored
as glycogen has been used up 1,3-Biphosphoglycerate

3-Phosphoglycerate
• Important precursors of glucose in animals
are: lactate, pyruvate, glycerol and amino 2-Phosphoglycerate

acids (alanine and glutamine) Phosphoenolpyruvate (PEP)

Pyruvate kinase

Pyruvate

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Glucose

hexokinase

Gluconeogenesis Glucose 6-phospate

3 irreversible (i.e.
Fructose 6-phospate cannot be reversed in
• Gluconeogenesis occurs largely in the liver Phosphofructokinase-1 gluconeogenesis)
(and to a smaller extent in the renal cortex) Fructose 1, 6-phospate
reactions of GLYCOLYSIS

Dihydroxyacetone phosphate Glyceraldehyde 3-phosphate

• 7/10 enzymatic reactions of gluconeogenesis


1,3-Biphosphoglycerate
are the reverse of glycolysis reactions
3-Phosphoglycerate

• 3 reactions in glycolysis are irreversible and 2-Phosphoglycerate


cannot be used in gluconeogenesis
Phosphoenolpyruvate (PEP)

Pyruvate kinase

Pyruvate

Glucose Glucose
Gluconeogenesis: 1st Bypass
Bypass 3 Bypass 3
Glucose 6-phospate • In Glucose 6-phospate

GLUCONEOGENESIS,
Fructose 6-phospate these 3 reactions are Fructose 6-phospate

Bypass 2
‘bypassed’ by a Bypass 2
Fructose 1, 6-phospate
separate set of Fructose 1, 6-phospate
enzymes
• The bypass reactions
Dihydroxyacetone phosphate Glyceraldehyde 3-phosphate Dihydroxyacetone phosphate Glyceraldehyde 3-phosphate
are highly exergonic
and cannot be
1,3-Biphosphoglycerate 1,3-Biphosphoglycerate
reversed in glycolysis
3-Phosphoglycerate 3-Phosphoglycerate

2-Phosphoglycerate 2-Phosphoglycerate

Phosphoenolpyruvate (PEP) Phosphoenolpyruvate (PEP)

Bypass 1 Bypass 1
Pyruvate Pyruvate

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Glucose
Gluconeogenesis: 1st Bypass Glucose
Gluconeogenesis: 2nd Bypass
Bypass 3
Glucose 6-phospate Glucose 6-phospate

• When lactate is the


Fructose 6-phospate precursor for pyruvate, Fructose 6-phospate

Bypass 2 the pathway (pyruvate Mg2+ Fructose 1,6-bisphosphatase


Fructose 1, 6-phospate
PEP) is much shorter Fructose 1, 6-phospate

Dihydroxyacetone phosphate Glyceraldehyde 3-phosphate Dihydroxyacetone phosphate Glyceraldehyde 3-phosphate


• Lactate conversion to
pyruvate produces
1,3-Biphosphoglycerate NADH in the cytosol so 1,3-Biphosphoglycerate

malate export to
3-Phosphoglycerate cytosol is not really 3-Phosphoglycerate
necessary
2-Phosphoglycerate 2-Phosphoglycerate

Phosphoenolpyruvate (PEP) Oxaloacetate Phosphoenolpyruvate (PEP)

Pyruvate Oxaloacetate Malate Pyruvate

Glucose
Gluconeogenesis: 3rd Bypass
Mg2+ Glucose 6-phosphatase
Glucose 6-phospate
Gluconeogenesis
• Glucose 6-phosphate is
Fructose 6-phospate
dephosphorylated by • The intermediates in the TCA cycle; citrate,
Glucose 6-phosphatase isocitrate, α-ketoglutarate, succinyl CoA,
Fructose 1, 6-phospate
to yield free glucose
succinate, fumurate, and malate; all can be
Dihydroxyacetone phosphate Glyceraldehyde 3-phosphate
• Glucose 6-phosphatase
oxidised to pyruvate
1,3-Biphosphoglycerate
is Mg2+-dependent and
is found in hepatocytes
3-Phosphoglycerate and renal cells but NOT • Thus the intermediates of the TCA cycle can all
present in muscles or be used to synthesise glucose via the
2-Phosphoglycerate brain gluconeogenesis pathway
Phosphoenolpyruvate (PEP)

Pyruvate

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Glucose
Gluconeogenesis
Gluconeogenesis Summary:
Glucose 6-phospate

Fructose 6-phospate
Glucose

Fructose 1, 6-phospate

Dihydroxyacetone phosphate Glyceraldehyde 3-phosphate

1,3-Biphosphoglycerate Pyruvate

3-Phosphoglycerate

citrate, isocitrate,
2-Phosphoglycerate
α-ketoglutarate,
succinyl CoA,
succinate,
Phosphoenolpyruvate (PEP) Oxaloacetate Lactate
fumurate, malate Amino acids

Pyruvate Oxaloacetate Malate

Gluconeogenesis The Glucose-Alanine Cycle Gluconeogenesis


The Cori Cycle
• In the Cori (Glucose-Lactate) • The liver cells then
cycle, anaerobic glycolysis in convert lactate to The enzyme Alanine
aminotransferase
RBCs or muscle tissue produces glucose via (ALT) can transfer an
lactate which is transported up- gluconeogenesis; amino group from
glutamate to
taken by the liver the glucose can Glutamate Glutamate
pyruvate to form
α-ketoglutarate
then enter the α-ketoglutarate
alanine
bloodstream and
be transported to
cells or tissues for
• Alanine formed in the muscles is transported to the liver.
use
• Liver ALT converts alanine to pyruvate coupled with the formation of
glutamate from α-ketoglutarate
• Pyruvate can then be used to synthesize glucose via the gluconeogenesis.
• The glucose produced can be transported via the blood to cells and tissues

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Clinical Aspects Clinical Aspects


• Glucose is continuously filtered by the • In hyperglycemia (as in diabetes mellitus),
glomeruli but is normally completely the glomerular filtrate may contain more
reabsorbed in the renal tubules by active glucose than can be reabsorbed, resulting in
transport glucosuria

• The capacity of the tubular system to • Glucosuria occurs when the venous blood
reabsorb glucose is limited to a rate of glucose concentration exceeds the renal
about 350 mg/min threshold for glucose (9.5–10.0 mmol/L)

Clinical Aspects Clinical Aspects

• During pregnancy, foetal glucose • Premature and low birth-weight babies have
consumption increases with the risk of little adipose tissue
maternal and possibly foetal hypoglycaemia
• Therefore they are not able to generate
alternative fuels such as free fatty acids or
• Risk of hypoglycaemia is greater at this time ketone bodies during the transition from foetal
especially during long intervals between dependency to the free-living state
meals or at night
• Thus premature and low birth-weight babies
are more susceptible to hypoglycaemia

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CARBOHYDRATE METABOLISM CARBOHYDRATE METABOLISM

GLYCOGEN GLYCOGEN

Glycogenolysis Glycogenesis Glycogenolysis Glycogenesis

GLUCOSE GLUCOSE Pentose Phosphate


pathway
Ribose 5-phosphate,
NADPH

Glycolysis Gluconeogeneis Glycolysis Gluconeogeneis

PYRUVATE PYRUVATE

The Pentose Phosphate Pathway Glucose 6-phospate

Glucose 6- NADP+
• An alternate route for glucose metabolism phosphate
dehydrogenase

• Also known as Hexose Monophosphate Shunt NADPH + H+

Phosphogluconolactone
Glyceraldehyde 3-phosphate Glycolysis

• This pathway does not generate ATP but is


important for the production of: Ribulose 5-phosphate Xylulose 5-phosphate Fructose 6-phosphate

1. NADPH + H+
2. Ribose 5’-phosphate Ribose 5-phosphate

de novo synthesis
PRPP
of nucleotides

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Clinical Aspects Glutathione peroxidase reaction


• Genetic deficiency of glucose-6-phosphate • Glutathione peroxidase (in erythrocytes ) is
dehydrogenase (G6PD), results in impairment dependent upon a supply of NADPH
of NADPH generation
• NADPH in erythrocytes can be formed only via
• Deficient NADPH manifests as red cell
the pentose phosphate pathway
hemolysis (hemolytic anemia) when
susceptible individuals are subjected to
oxidants, such as primaquine, sulfonamides or • Glutathione peroxidase reduces organic
fava beans (Vicia fava—hence the term peroxides and H2O2 as part of the body’s
favism) defense against lipid peroxidation

The Pentose Phosphate Pathway Role of the pentose phosphate pathway in the Glutathione
peroxidase reaction of erythrocytes
• Oxidation here is achieved by dehydrogenation

• NADP+ is used as the hydrogen acceptor in the (Oxidized Glutathione)

pentose phosphate pathway

• The enzymes of the pathway are cytosolic (Reduced Glutathione)

• Deficiency, of the enzyme, Glucose-6-phosphate


dehydrogenase (G6PD), results in impairment of • The selenium-containing enzyme glutathione peroxidase
catalyzes the destruction of H2O2 and lipid hydroperoxides by
NADPH production reduced glutathione, protecting membrane lipids and
hemoglobin against oxidation by peroxides

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Clinical Aspects CARBOHYDRATE METABOLISM


• Genetic deficiency of G6PD results in
impairment of NADPH generation which GLYCOGEN
manifests as red cell hemolysis (hemolytic
anemia) when susceptible individuals are Glycogenolysis Glycogenesis
subjected to oxidants
Glucuronic
acid
Uronic Acid
pathway GLUCOSE Pentose Phosphate
pathway
Ribose 5-phosphate,
NADPH

• Oxidants known to cause hemolysis in G6PD


individuals include: primaquine, aspirin, or Glycolysis Gluconeogeneis
sulfonamides or fava beans (Vicia fava—hence
the term favism) PYRUVATE

Uronic Acid Pathway Cellular Respiration


Glucose
Mg2+ hexokinase/ • another alternative pathway for the
glucokinase
oxidation of glucose
Glucose 6-phosphate O2
Glucose
phosphoglumutase
• does not produce ATP

Glucose 1-phosphate UTP • Generates activated form of


Glucuronic acid, UDP-glucuronate KREB’S ELECTRON
UDP-glucose GLYCOLYSIS TRANSPORT CHAIN
pyrophosphorylase CYCLE* (Oxidative Phosphorylation)

2Pi PPi 2NAD+


H2O
UDP-Glucose e- CO2 CO2 e- H2O
2NADH + 2H+ Pyruvate
UPD-glucose dehydrogenase
ATP
UDP-Glucuronate Glucuronides, NADH ATP NADH,
(Conjugation reactions
in the Liver)
FADH2
Acetyl-CoA
Ascorbic acid Glucuronic acid Proteoglycans,
Glycosaminoglycans

*also known as the TCA cycle or the Citric Acid Cycle

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STUDY QUESTIONS
REFERENCES
• Define metabolism, anabolism and catabolism.
• Murray RK, Granner DK, Mayes, Rodwell VW. Harper’s Biochemistry • What is glycolysis? What is the significance of glycolysis?
24th Edition 1996 • What is aerobic glycolysis? What is anaerobic glycolysis?
• Describe the glycolysis in erythrocytes. What is 2,3 BPG?
• Delvin TM. Textbook of Biochemistry with Clinical Correlations 4th • List the components of the pyruvate dehydrogenase complex. What
Edition 2001 coenzymes and B vitamins are needed by this complex?
• What is the Citric Acid Cycle? What is its significance?
• Nelson DL and Cox MM. Lehninger Principles of Biochemistry • Describe glycogenesis and glycogenolysis.
3rd Edition, 2000, Worth Publishers, New York. • How are glycogenesis and glycogenolysis pathways regulated?
• What is gluconeogenesis?
• Koolman J and Roehm KH. Colour Atlas of Biochemistry 2nd Edition • What reactions of the glycolysis pathways are not reversed in
2005 gluconeogenesis?

STUDY QUESTIONS

• What is the Cori cycle? What is the significance of the Cori Cycle?
• What is the Alanine Cycle? What is the significance of Alanine
Cycle?
• What is the significance of the Pentose Phosphate Pathway?
• What is the significance of the Uronic acid pathway?
• What disease conditions may occur as a result of defects in
glycolysis?
• What disease conditions may occur as a result of defects in
glycogenesis?
• What disease conditions may occur as a result of defects in
glycogenolysis?
• What disease conditions may occur as a result of defects in
glyconeogenesis?

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