CARBOHYDRATE

METABOLISM
 CARBOHYDRATE METABOLISM

The process in brief:

1.  Starch is the principal carbohydrates ingested by humans.

Digestion of starch begins in the mouth where the enzyme
ptyalin (an amylase and maltase) catalyzes the hydrolysis of
starch into dextrins. Sucrose and lactose are not digested in
the mouth.
2.  Ptyalin continues to function as food passes through the
esophagus, but is quickly inactivated when it comes in contact
with the acidic environment of the stomach.
 CARBOHYDRATE METABOLISM

The process in brief:

3.  The primary site of carbohydrate digestion is the small intestine where
another amylase, amylopsin converts the remaining starch molecules
along with the dextrins to maltose. Maltose is then cleaved into 2
glucose units by maltase; sucrose into glucose and fructose by sucrase;
and lactose, to glucose and galactose by lactase.
 CARBOHYDRATE METABOLISM

The process in brief:

4.  Ultimately, the complete hydrolysis of polysaccharides and disaccharides

produce 3 monosaccharide units: glucose, fructose, and galactose, which are
then absorbed by active transport through the walls of the small intestine into the
bloodstream.
 CARBOHYDRATE METABOLISM

The process in brief:

5.  Following absorption the monosaccharides are carried by the portal vein to
the liver where galactose and fructose are enzymatically converted to
glucose.

6. The glucose may then pass into the general circulatory system to be
transported to the tissues or converted to glycogen reserve in the liver.
 CARBOHYDRATE METABOLISM

The process in brief:

7.  The glucose in the tissues may be:

a) oxidized to CO2 and H2O (ATP)

b) converted to fat
c) converted to muscle glycogen
Major pathways in
carbohydrate
metabolism
 ATP
reducing power
building blocks

de novo aerobic oxidation

synthesis
glucose anaerobic oxidation

glycogen
 alcoholic
fermentation
anaerobic oxidation
of glucose:
aerobic oxidation
of glucose

no O2 more energy, but

take longer time

lactic acid
fermentation
 Steps of Respiration
S  Glycolysis: cytoplasm

S  Citric Acid Cycle: mitochondrial matrix

S  Oxidative

Phosphorylation:
Inner
membrane
ANAEROBIC OXIDATION

Ø  In the formation of pyruvate

from glucose, one molecule
of NAD+ is reduced to
NADH for each molecule of
pyruvate formed.

Ø  To regenerate NAD+, two

electrons are transferred from
each NADH molecule to an
acceptor molecule. When
oxygen supplies are low in
muscle cells, the acceptor is
pyruvic acid, and lactic acid is
formed.

Ø  In yeasts, acetaldehyde is the

acceptor, and ethanol is formed.
Ø  This anaerobic
fermentation is the basis of
beer and wine production.
 Oxidation / Reduction
S  When electrons are transferred to oxygen (very
electronegative), they release energy that the cell
can use.
Important Respiration Terms

S  NAD+ (nicotinamide adenide

dinucleotide): coenzyme electron
acceptor

S  NAD+ becomes NADH

S  Electron transport chain

S
Ø  The coenzyme flavin adenine dinucleotide (FAD) can accept one or two hydrogen atoms. The addition of
one electron together with a proton (i.e., a hydrogen atom) generates a semiquinone intermediate. The
semiquinone is a free radical because it contains an unpaired electron (denoted by a blue dot), which is
delocalized by resonance to all the flavin ring atoms. The addition of a second electron and proton (i.e.,
a second hydrogen atom) generates the reduced form, FADH2. Flavin mononucleotide (FMN) is a
related coenzyme that contains only the flavin – ribitol phosphate part of FAD (highlighted in blue).
 GLYCOLYSIS

S  The  first  stage  of  glucose  metabolism  in  organisms  from  bacteria  to  
humans  is  called  glycolysis.    

S  It  is  series  of  reac8ons  in  the  cytoplasm  that  converts  the  6-­‐carbon  
glucose  molecule  into  two  3-­‐carbon  pyruvate  fragments.    

S  also  called  Embden-­‐Meyerhof  Pathway,  aCer  the  scien8sts  who  

elucidated  the  degrada8on  of  glucose  and  glycogen  in  the  absence  of  O2.    

S  an  anaerobic  process;  each  step  takes  place  without  O2.      

Stage 1, which is the conversion of
glucose into fructose 1,6-
bisphosphate. The strategy of these
initial steps in glycolysis is to trap the
glucose in the cell and form a
compound that can be readily
cleaved into phosphorylated three-
carbon units.
Stage 2 is the cleavage of the fructose
1,6-bisphosphate into two three-
carbon fragments. These resulting
three-carbon units are readily
interconvertible.
Stage 3, ATP is harvested when the
three-carbon fragments are oxidized to
pyruvate.
General description of glycolysis
GLYCOLYSIS
What is the course of glycolysis?

From glucose to pyruvate, there are

10 steps, divided into 3 stages,
occurred in cytosol.
Glycolysis -is the sequence of
reactions that metabolizes one
molecule of glucose to two
molecules of pyruvate with the
concomitant net production of two
molecules of ATP.
 The process of glycolysis

consists of three
steps:
•  phosphorylation
•  isomerization
•  second
phosphorylation
Two ATP molecules are
needed .
 GLYCOLYSIS

S  one  of  its  advantages,  the  body  can  obtain  energy  from  glycolysis  
quickly,  without  wai8ng  for  a  supply  of  O2  to  be  carried  to  the  cells.    

S  occurs  in  cells  lacking  mitochondria,  e.g.,  erythrocytes  and  in  
certain  skeletal  muscle  cells  during  intense  muscle  ac8vity.    

S  produces  a  net  gain  of  2  ATP  by  a  process  called  substrate-­‐level  
phosphoryla8on.  
 Energy-Harvesting Steps

An enzyme passes a high-energy phosphate to ADP to

produce ATP
 The process of
glycolysis
Kinases are enzymes that catalyze the transfer of a phosphoryl group
from ATP to an acceptor.

requires Mg2 +

building block metabolic

intermediate
 The process of glycolysis

The isomerization of glucose 6-phosphate to fructose 6-

phosphate is a conversion of an aldose into a ketose.
Ø  The reaction catalyzed by phosphoglucose isomerase includes additional
steps because both glucose 6-phosphate and fructose 6-phosphate are
present primarily in the cyclic forms. The enzyme must first open the six-
membered ring of glucose 6-phosphate, catalyze the isomerization, and
then promote the formation of the five-membered ring of fructose 6-
phosphate.
The process of
glycolysis

Ø  This reaction is catalyzed by

This enzyme plays a central
phosphofructokinase (PFK), an role in the integration of
allosteric enzyme that sets the much of metabolism
pace of glycolysis.

The prefix bis- in bisphosphate means that two separate monophosphate

groups are present, whereas the prefix di- in diphosphate (as in adenosine
diphosphate) means that two phosphate groups are present and are
connected by an anhydride bond.
 Free-Energy Changes of Glycolytic Reactions in
Erythrocytes
Three (3) reactions of glycolysis are essentially irreversible in vivo.
Summary of GLYCOLYSIS

Energy-Harvesting Steps: 4 ATP

Energy-Investment Steps: - 2 ATP
Net ATP production : 2 ATP
In  carbohydrate  metabolism  there  are  at  least  2  direc8ons  that  the  
product  pyruvate  may  take:    
a.      If  there  is  adequate  oxygen,  an  aerobic  pathway  is  followed  and  
 
pyruvate  enters  the  Krebs  cycle.  

b.  If  there  is  insufficient  oxygen  available,  an  anaerobic  pathway  is  
 
followed  and  pyruvate  undergoes  a  series  of  reac8ons  to  produce  lac8c  acid.  

•  One  molecule  of  glucose  is  converted  to  two  molecules  of  
pyruvate.  
•  Under  aerobic  condi8ons,  pyruvate  is  oxidized  to  CO2  and  H2O  by  
the  citric  acid  cycle  and  oxida8ve  phosphoryla8on.    
•  Under  anaerobic  condi8ons,  lactate  is  produced,  especially  in  
muscle.    
•  Alcoholic  fermenta8on  occurs  in  yeast.  
•  The  NADH  produced  in  the  conversion  of  glucose  to  pyruvate  is  
reoxidized  to  NAD+  in  the  subsequent  reac8ons  of  pyruvate.  
S  Pyruvate  is  most  commonly  
metabolized  in  one  of  three  
ways,  depending  on  the  type  
of  organism  and  the  presence  
or  absence  of  O2  

•  Lactate  fermenta8on  is  the  anaerobic  metabolism  that  occurs  in  exercising  muscle.    

•  Bacteria  also  use  lactate  fermenta8on  in  the  produc8on  of  yogurt  and  cheese.    

•  Yeast  ferment  sugars  of  fruit  and  grains  anaerobically,  using  pyruvate  from  glycolysis  
by the way
 PREPARATORY
REACTION

Pyruvate Conversion to acetyl-CoA

§  Occurs twice for each glucose molecule
§  Produces the substrate , acetyl CoA, that enters the
subsequent citric acid or Krebs cycle.
 Production of Acetyl-CoA
(Activated Acetate)

§  An irreversible oxidation process

§  A combined dehydrogenation and decarboxylation of pyruvate to the
acetyl group of acetyl-CoA
§  Pyruvate is oxidized to 2-carbon acetyl-CoA and releases CO2 .
§  High energy electrons are removed from pyruvate and taken up by
NADH. NAD+ accepts a hydrogen atom, producing NADH.
TRICARBOXYLIC  ACID  (TCA)  CYCLE  
 
S  also  called  KREBS  CYCLE  or  CITRIC  ACID  CYCLE  

S  aerobic  metabolism  

S  Takes  place  in  the  mitochondria  where  acetyl  CoA  is  oxidized  to  CO2  and  
H2O  

S  Amphibolic  (plays  a  role  in  both  catabolism  and  anabolism)  

 Citric Acid/Krebs Cycle
S  Citric acid cycle, tricarboxylic
acid (TCA) cycle or the Krebs
cycle (after its discoverer,
Hans Krebs)
S  Occurs in the matrix of the
mitochondria
•  Eight enzyme-catalyzed steps

S  A nearly universal central

catabolic pathway in which
compounds derived from the
breakdown of carbohydrates,
fats, and proteins are oxidized
to CO2, with most of the
energy of oxidation
temporarily held in the
electron carriers FADH2 and
NADH.
Krebs Cycle
Krebs Cycle (step 1)

§ Formation of Citrate
§ Irreversible condensation of two-
carbon acetyl-CoA with four
carbon oxaloacetate to form six-
carbon citrate

The  early  discovery  of  citric  acid  is  the  reason  the  pathway  is  called  
citric  acid  cycle.  Note  that  this  step  regenerates  CoASH.  
 Krebs Cycle (steps 2a & 2b)

§  Reversible isomerization of Citrate to

Isocitrate
§  The single enzyme aconitase catalyzes the
successive elimination and reincorporation
of a molecule of water with a net result of
isomerization of citric to isocitric acid
Krebs Cycle (step 3)
§ Formation of α-Ketoglutarate and CO2
§  Oxidative decarboxylation of isocitric acid to α-ketoglutaric
acid
§  Isocitrate dehydrogenase catalyzes oxidative
decarboxylation of isocitrate to form
α-ketoglutarate
§  Mn2+ in the active site interacts with the carbonyl group of
the intermediate oxalosuccinate, which is formed transiently
but does not leave the binding site until decarboxylation
converts it to α-ketoglutarate.
 Krebs Cycle (step 4)
§ Oxidative decarboxylation
§  Converts C5 α -Ketoglutarate to C4
Succinyl-CoA and CO2 by the action of the α-
ketoglutarate dehydrogenase complex
§  The only non-reversible reaction in the Krebs
Cycle and, as such, prevents the cycle from
operating in the reverse direction
§  NAD serves as electron acceptor and CoA as
the carrier of the succinyl group.
 Krebs Cycle (step 5)
§ Formation of Succinate
§  Reversible conversion of C4 Succinyl-CoA to
C4 Succinate by the action of succinyl-CoA
synthetase or succinic thiokinase.
§  The process requires the participation of the
cofactor GDP.
§  GTP can react with ADP to generate ATP;.
GTP + ADP à GDP + ATP
ΔG = 0 kJ/mol
ATP and GTP are energetically equivalent

§  The step regenerates CoASH

 Krebs Cycle (step 6)
§ Formation of Fumarate
§  Reversible Oxidation of C4 Succinate to C4
Fumarate by the action of flavoprotein
succinate dehydrogenase
§  The only step in the cycle catalyzed by the
coenzyme FAD, not by NAD+
§  Involves dehydrogenation of succinate.
 Krebs Cycle (step 7)

§ Formation of L-Malate
§  Reversible Hydration (addition of
water across the double bond) of
C4 Fumarate to C4 Malate by the
action of Fumarase or fumarate
hydratase
§  Fumarase is highly stereospecific
producing only L-malate
 Krebs Cycle (step 8)
§ Regeneration of Oxaloacetate
§ The step involves the dehydrogenation
of L-malic acid to oxaloacetic acid by the
NAD-linked L-malate dehydrogenase
signifying the completion of the cycle.
§ Reversible Oxidation
(3 NADH/ mol acetyl CoA) x (2 acetyl CoA /mol glucose)
= 6 NADH /mol glucose
(1 FADH2 / mol acetyl CoA) x (2 acetyl CoA /mol glucose)
= 2 FADH2 /mol glucose /mol glucose
(1 ATP/ mol acetyl CoA) x (2 acetyl CoA /mol glucose)
= 2 ATP/mol glucose
Stoichiometry of Coenzyme Reduction and ATP Formation in the Aerobic Oxidation of Glucose via
Glycolysis, the Pyruvate Dehydrogenase Complex Reaction,
the Citric Acid Cycle, and
Oxidative Phosphorylation

-1
-1
4 or 6**
2
2
6
6
6
2
4
6
36-38

*This is calculated as 3 ATP per NADH and 2 ATP per FADH2. A negative value indicates
consumption.
** This number is either 4 or 6, depending on the mechanism used to shuttle NADH equivalents
from the cytosol to the mitochondrial matrix.
Summary  of  reac8ons  in  Citric  acid  cycle  

 
Summary  of  reac8ons  in  Citric  acid  cycle  
S  Pyruvate  dehydrogenase  complex:  

Pyruvate  +  CoA-­‐SH  +  NAD+    →  Acetyl-­‐CoA  +  NADH  +  CO2  +  H+  

S  Citric  acid  cycle:  

 
 
S  Overall  reac8on:  

S  Eventual  ATP  produc8on  per  pyruvate:  

Important  features  of  the  cycle:  
 
S  The  reac8ons  of  the  cycle  takes  place  in  the  mitochondrial  matrix,  except  the  succinate  
dehydrogenase  reac8on  that  involves  FAD.    

S  The  “fuel  “  for  the  cycle  is  acetyl  CoA,  obtained  from  the  breakdown  of  carbohydrates,  fats,  
and  proteins.  

S  Four  of  the  cycle  reac8ons  involve  oxida8on  and  reduc8on.  The  oxidizing  agent  is  either  NAD+  
(3x)  or  FAD  (once).    

S  In  redox  reac8ons,  NAD+  is  the  oxidizing  agent  when  a  carbon-­‐oxygen  double  bond  is  formed;  
FAD  is  the  oxidizing  agent  when  a  carbon-­‐carbon  double  bond  is  formed.  

S  The  three  NADH  and  the  one  FADH2  that  are  formed  during  the  cycle  carry  electrons  and  H+  to  
the  electron  transport  chain  through  which  ATP  is  synthesized.  

 
Important  features  of  the  cycle:  

 
S  Two  carbon  atoms  enter  the  cycle  as  acetyl  unit  of  the  acetyl  CoA,  and  two  
carbon  atoms  leave  the  cycle  as  two  molecules  of  CO2  

S  Four  B  vitamins  are  necessary  for  the  proper  func8oning  of  the  cycle:  riboflavin  
(in  both  FAD  and  α-­‐ketoglutarate  dehydrogenase  complex),  nico8namide  (in  
NAD+  ),  pantothenic  acid  (in  CoASH),  and  thiamin  (in  α-­‐ketoglutarate  
dehydrogenase  complex).  

S  One  high-­‐energy  GTP  molecule  is  produced  by  phosphoryla8on.