Lecture 1
Carbohydrate (CHO)Metabolism
By Prof.Dr. Munaf Salih Daoud
1- Glycolysis
Objectives:
a- Describe the role of ATP as an energy currency.
b- Explain what CHO are involved in by having an
overview to their role in human metabolism.
c- Explain glycolysis ( aerobic & anaerobic ) and
identify their importance.
d- Explain its regulation and the link with other
pathways through intermediate compounds.
Source of Energy ( E ):
The ultimate source of E for all living matters is the
sunlight which converts CO2 + H2O into CHO( starch) in
plants. Starch converts into glucose (Glc or G ) in the
body which give E on oxidation.
Plants(CO2+H2O)-sunlight photosynthesis→ Glc
→ starch-body→Glc-oxidation with ADP+Pi→
ATP ( E is conserved in ATP )
ATP is a nucleotide ( Adenine+Ribose+ 3
phosphates, it has 2 high-energy phosphate
bonds ( ~P ). It acts as a donor of a ~P to form
compounds of less free E of hydrolysis ( ∆G) like
Glc6-P , Fructose(Frc)6-P …etc.
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 ADP is another nucleotide ( with one ~P ) can
accept ~P from compounds of higher ∆G
like phosphoenolpyruvate(PEP) or creatine
–P found in muscle to form ATP in the
ATP/ADP cycle which shows the link
between processes that generate ~P &
those that utilize it.
Three major sources of ~P take part in E
conservation (E capture).
1-Glycolysis 2- TCA cycle 3- ETC&Ox.Phosph.
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 Phosphagen- act as storage forms of ~P e.g.
Creatine~P found in skeletal
muscles,heart,spermatozoa,brain).In rapid ATP
utilization as a source of E for muscle
contraction,phosphagens act as a donor of ~P to
maintain its concentration & when ATP/ADP ratio
is high,then phosphagens increase acting as a
store.
Biological E are either:
Exergonic- ∆G is negative, so reactions
proceeds spontaneously with loss of free E ( E
liberating) reactions. This occurs in Catabolic
Reactions( breakdown of molecules)
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Glycogen→Glc→CO2 + H2O (Glycogenolysis &
Glycolysis)
Endergonic- ∆G is positive so reactions proceeds
only if freeE can be gained (E is needed ). This
occurs in Anaerobic Reactions ( Synthesis of
molecules).
Glc → Glycogen ( glycogenesis)
Besides ATP,other nucleotides of high ~P are
GTP,CTP,& UTP used to supply E in protein,lipid,
& polysaccharide synthesis,respectively.Each is
formed by combination of ATP with GDP,CDP,&
UDP in order by a kinase enzyme.
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CHO Metabolism
1- carried out in every cell in the body.
2- Found in cytoplasm ( Cytosol).
Glycolysis,Glycogenesis,& Glycogenolysis.
in mitochondria( Membranes& Matrix), TCA
cycle, ETC& OX Phosph..
in both , Gluconeogenesis.
3- Alternative pathways are HMP shunt , Uronic acid
pathway.
1- Glycolysis
. Used by all tissues for oxidation ( breakdown ) of
Glc in 9 reactions to give E ( ATP )& intermediates for
other metabolic pathways ( Link ).
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Aerobic ( in presence of O2 ) Glc→ 2 pyruvates
or pyruvic acids.
Anaerobic ( in absence of O2 ) → 2 lactates
or lactic acids.
Reactions:
Glc(6-C ) with 1 ATP→ Glc6-P by
hexokinase(HK) or glucokinase(GK) then
→Frc6-P by isomerase then with 1 ATP →
Frc 1,6 bisP ( 6-C) by PFK-1 then cleaved
into 2 (3-C ) by Aldolase A ( cleavage
enzyme) → Glyceraldehyde 3-P (3-C)+
dihydroxyacetone phosphate DHAP(3-C)
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This step is interconvertible & 2( Glycerald. 3-P) is
formed by isomerase then with 2NAD by its
dehydrogenase → 2NADH + 1,3
bisphosphoglycerate (1,3bisPG) which combine
with 2ADP by kinase → 2(3PG) + 2ATP then →
2(2PG)by mutase then → PEP by enolase then
with ADP → 2ATP + 2 pyruvates by pyruvate
kinase(PK) ( Aerobically)….The 2 pyruvates with
2NADH by lactate dehydrogenase ( LDH) → 2NAD
+ 2 lactates ( Anaerobically )
[ N.B. 1,3 bisPG by mutase →2,3 bisPG then →by
phosphatase 3PG ,this occurs in RBCs].
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The 2,3biPG of high concentration (4mM) equal to
Hemoglobin ( Hb) binds to it & act as regulator of O2
transport by decreasing affinity of Hb to O2 thus
allowing O2 release in tissue capillaries .
▪ E production :
Aerobic glycolysis produces 2ATP+2NADH(
give 4 ATP if moves through Glycerol 3-Pshuttle
or 6 ATP if through malate shuttle) i.e. 6-8 ATP
per 1 Glc oxidized to 2 pyruvates.
Anaerobic glycolysis produces 2 ATP(
produced by substrate level phosphorylation.In
its pathway which occurs in exercised muscle (
due to lack of O2 or Hypoxia) or in RBCs ( lack of
mitochondria),the NADH cannot be oxidized
through ETC but used by pyruvate to form lactate by LDH
.This enzyme have Clinical significance & have 5
isoenzymes.The increased level of blood lactate above
normal limit is known as Lactic Acidosis. (a pathological
condition of many causes).
▪Anaerobic Glycolysis occurs in exercised
muscle,RBCs,Cancer cells in CancerCachexia . During
extended muscle exercise, ↑[lactate] move in blood to
liver to be reconverted to pyruvate which form Glc
by Gluconeogenesis ( Cori ̛s cycle).
Aerobic Glycolysis occurs in most tissues ( organs )
when O2 is available but it is low in Cardiac muscles
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Ischemic heart diseases.The brain is highly dependent
on Glc for its E supply & needs continuous supplement .
Regulation :
The key enzymes are HK,PFK-1 & PK .
1- PFK-1 is inhibited by ATP & citrate and activated by
cAMP,Frc6-P,Frc 2,6 bisP ( in liver).
2- Allosteric activation or inhibition of HK,PFK-1 &PK
by phosphorylation & dephosphorylation ( short- term
influences , minutes-hours)
3- Hormonal influence on the amount of enzyme
synthesized ( long- term increase of activity by 10-20
folds , hours-days).
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4- Well-fed ( after a meal of CHO) or high insulin
→high enzyme activity.
5- Starvation or Diabetes →low enzyme
activity.
6- PK , activated by Frc1,6 bisP & inhibited
by ATP, glucagon & epinephrine( adrenaline).
☻ Genetic defect , Inherited deficiences of
HK&PK cause Hemolytic Anemia due to
↓[ATP] important in maintaining the biconcave
shape of RBCs membranes and ↓[ 2,3 bisP]
important in O2 release in tissue capillaries .
☻glycolysis is inhibited by
iodoacetate,arsenate& fluoride.
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Other CHO that enters glycolysis:
1- Glycogen through formation of Glc6-P (
muscle).
2- Fructose through formation of Frc1-P by
fructokinase ( liver,kidnney,intestine,testis) i.e.
Fructolysis.Frc1-P is cleaved by Aldolase B (
predominantly found in liver) & bypass the main
regulatory steps catalyzed by PFK-1 resulting in the
formation of more pyruvate ( and Acetyl CoA) than
is required for ATP formation.
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