Dr.H.MOHAMMAD HANAFI, MBBS (Syd).MS.

MEDICAL FACULTY UNAIR

Blog : http//mhanafi123.wordpress.com

INTRODUCTION
Carbohydrate is a staple food of
Indonesian, as many others, specially
of Asian and African countries. In
general, the source of carbohydrate in
food derived from rice, but some are
derived from corn, sago, cassava,
potatoes, sweet potatoes, and bananas.

 In rice amylum is the major

component. Others are minerals,
vitamins, and fibers

Amylum : amylopectin and

amylose
Classification of Carbohydrate
Hetero polysaccharides
Homo polysaccharides
Oligosaccharides
Disaccharides
Monosaccharide's

Digestion and absorption

Amylase pancreas (alfa amylase)
Endopolysaccharidase : break up alfa
link ( 1 4 ), except on the tip of
polymers, and near the branch points.
Result of digestion : glucose, maltose,
maltotriose, iso maltose, and
oligosaccharides (limit dextrins)
Intestinal enzymes : maltase, lactase,
sucrase, limit dextrase etc.
Active absorption : glucose and galactose

Blood & guts: Putting it together for

glucose transport
glucose

Fig. 11-44

Transfer of Glucose and Other Sugars

Through The Lipid Bilayer
Because the lipid bilayer of the eucaryotic plasma
membrane is impermeable for hydrophilic molecules,
glucose is transported across the plasma membrane
by membrane associated carrier proteins, glucose
transporters. There are 2 different types of
transporter proteins, which mediate the transfer of
glucose and other sugars through the lipid bilayer:
+

Na -coupled carrier system (SGLT)

The facilitative glucose transporters
(GLUT)

PATH WAYS IN CARBOHYDRATE

METABOLISM
Glycolysis
Glycogenesis
Glycogenolysis
Pyruvate oxidation
TCA Cycle
(final common pathway)

Hexose Mono-phosphate
Shunt or Pentose
Phosphate Pathway
Gluconeogenesis
Uronic Acid pathway
Fructose and Galactose
metabolism
Hexosamine

GLYCOLYSIS
Change : glucose pyruvate
glucose lactic acid
Function : produce ATP
Site : cytoplasm
Aerobic glycolysis forms 7 ATP
Anaerobic glycolysis forms 2 ATP

Pyruvate

Lactate

G 6P

HEXOKINASE GLUCOKINASE
Found in all cells
except pancreas
Inhibited by ( G 6P )
Km for glucose low
Catalyze the reaction
Fructose (F) F 6P

Found in liver and

pancreas
G 6P has no effect
Km for glucose high
The only enzyme for
G G 6P

G 6P F 6P

Phosphofructokinase
6 CH OPO 2
2
3

1CH2OH

OH

ATP ADP

HO

3 OH

fructose-6-phosphate

6 CH OPO 2
2
3

Mg2+

1CH2OPO32

H
4

OH

HO

3 OH

fructose-1,6-bisphosphate

Regulator enzyme
PFK-1
F 6P F 1,6 BP One way reaction

PHOSPHO FRUCTO KINASE 1

( PFK 1 )
Activators :
ADP
AMP
Pi
NH3
F 2,6 BP
( fructose 2,6 Bis
Phosphate )
F6P

Inhibitors
ATP
Citric acid
2,3 BP Glycerate
( in erythrocytes)
Free Fatty Acid
Acetyl-CoA
Ketone bodies

Ketone bodies :
Acetoacetate
Betahydroxy Butyrate
Acetone
O

CCCCOOH
OH
|
CCCCOOH

CCC

UNIQUE ROLE OF 2,6 BP

In the liver
The most potent positive allosteric
activator for enzyme
Phosphofructokinase-1 (PFK-1),
and
It relieves inhibition of PFK-1
by ATP, and affinity for F 6 P
Inhibit Fructose 1,6-bisphosphatase
( Km for F 1,6 BP )

F 6P

F2,6 BP
PFK-2

cAMP Dependent
Protein Kinase
Protein Protein P
( few proteins )

Phosphofructokinase-2 (PFK-2) is also

a phosphatase (bifunctional enzyme)
Bifunctional enzyme has two activities:
6-phosphofructo-2-kinase activity, decreased by
phosphorylation
Fructose-2,6-bisphosphatase activity, increased by
phosphorylation

kinase
ATP

ADP

fructose-2,6-bisphosphate

fructose-6-phosphate
Pi

phosphatase

2
CH
OPO
1
2
3

2C

HO 3C
H 4C

Aldolase

2
CH
OPO
2
3
3

OH

2C

OH

1CH2OH

2
CH
OPO
2
3
6

fructose-1,6bisphosphate

O
1C

H 2C OH
2
CH
OPO
3
2
3

dihydroxyacetone glyceraldehyde-3phosphate
phosphate

Triosephosphate Isomerase

F 1,6 BP
Gld 3P + DHAP

Triosephosphate Isomerase
H
H

OH

H H

CH2OPO32

dihydroxyacetone
phosphate

OH
C
C

+ +

H H

OH

CH2OPO32

enediol
intermediate

O
C

OH

CH2OPO32

glyceraldehyde3-phosphate

In Glycolysis DHAP is converted into

glyceraldehyde -3P

Glyceraldehyde-3-phosphate
Dehydrogenase
H

+H
NAD+ NADH

1C

OH

+ Pi

2
CH
OPO
2
3
3

glyceraldehyde3-phosphate

OPO3

1C

OH

2
CH
OPO
2
3
3

1,3-bisphosphoglycerate

6. Glyceraldehyde-3-phosphate Dehydrogenase
catalyzes:
glyceraldehyde-3-P + NAD+ + Pi
1,3-bisphosphoglycerate + NADH + H+

If oxygen available Respiratory Chain

in function, by mean of Malate shuttle
system oxidizes NADH
in the resp. syst ; 2.5 ATP released
NAD+ recovered, catalyzed by
malate dehydrogenase
Enzyme glyceraldehyde 3P dehydrogenase
required NAD+ in function

If R. C. not in function,
NADH will reduces Pyruvate into Lactate

Exergonic oxidation of the aldehyde

in glyceraldehyde-3-phosphate, to a
carboxylic acid, drives formation of
an acyl phosphate, a "high energy"
bond (~P).
This is the only step in Glycolysis in
which NAD+ is reduced to NADH.

Phosphoglycerate Kinase
O

OPO32 ADP ATP O

O
1C

H 2C OH
2
CH
OPO
2
3
3

1,3-bisphosphoglycerate

Mg2+

H 2C OH
2
CH
OPO
2
3
3

3-phosphoglycerate

This phosphate transfer is reversible (low G), since

one ~P bond is cleaved & another synthesized.
The enzyme undergoes substrate-induced conformational
change similar to that of Hexokinase.

Phosphoglycerate Mutase
O

C
1

C
1

H 2C OH
3 CH2OPO3

H 2C OPO3
2

3-phosphoglycerate

3 CH2OH

2-phosphoglycerate

Phosphate is shifted from the OH

on C3 to the OH on C2.

Fluoride
(-)

Enolase

O
C

H 2 C OPO32
3 CH2OH

H
O

O
C
C

OH

O
1

OPO32

CH2OH

2C

OPO32

3 CH2

2-phosphoglycerate enolate intermediate phosphoenolpyruvate

Fluoride in tooth paste inhibits oral bacterial growth

F is also used in glucose determination

Pyruvate Kinase
O

O
C
1
C
2

ADP ATP

OPO32

3 CH2

phosphoenolpyruvate

O
C

O
1

OH

3 CH2

enolpyruvate

3 CH3

pyruvate

This phosphate transfer from PEP to ADP is spontaneous.

PEP has a larger G of phosphate hydrolysis than ATP.
Removal of Pi from PEP yields an unstable enol, which
spontaneously converts to the keto form of pyruvate.
Required inorganic cations K+ and Mg++ bind to anionic residues at
the active site of Pyruvate Kinase.

Pyruvate Kinase
activity
Activators :
F 1,6 BP
In the liver F 1,6 BP
able to abolish inhibition
of ATP and Alanine

Inhibitors :
ATP
Free Fatty Acid
Acetyl CoA
Ketone bodies
Alanine
(in liver only)

Protein Kinase (P.K.) controls in

Glycogen.
cAMP dependent Protein Kinase
activated by cAMP.
cAMP synthesized from ATP
enzyme adenylyl cyclase
Glucagon activates adenylyl
cyclase (through G protein)

cAMP Dependent Protein Kinase

inhibits Glycolysis in two sites
1. PFK-1, with
decreasing F2,6 BP.
PFK-2-P catalyzes
F2,6 BP F6P + Pi.
Active cAMP
Dependent P.K.
converts
PFK-2 PFK-2-P
( ATP ADP )

2.Inactive Pyruvate
Kinase
PEP P
Pyruvate Kinase
PK-P
Pyruvate Kinase is
phosphorylated by
cAMP Dependent P.K.
Pyruvate Kinase phosphate
(PK-P) is inactive

If oxygen available
for respiratory chain activity,
Pyruvate is the end product of Glycolysis
with 7 ATP as high energy phosphate.
( older textbook still counting as 8 ATP).
In unaerobic Glycolysis of certain type of muscle
for sprinters, lack of oxygen cause inactive
respiratory chain. NADH will reduces Pyruvate,
and Lactate is the final product of Glycolysis.
NAD+ is ready as coenzyme for Glyceraldehyde
3P dehydrogenase

Lactate Dehydrogenase
O

C
C

NADH + H+ NAD+

CH3

pyruvate

O
C
HC

OH

CH3

lactate

NAD+ is the target product. Lactate is the by product.

Lactate is one of the substrate of gluconeogenesis, will
be taken up by the liver and changed into glucose.

Glycolysis in Erythrocyte
No mitochondria
No Respiratory enzymes
NADH reduces Pyruvate into Lactate
2,3 BP Glycerate
drives oxygen dissociation of
Oxy hemoglobin to release Oxygen
inhibits PFK-1

In the tissue where

oxygen required
but not ATP,
1,3 BP Glycerate
is converted into
2,3 BP Glycerate

Lactate release .
Tissues that normally derive much of their
energy from glycolysis and produce
lactate include brain, gastrointestinal
tract, renal medulla, retina, and skin.
Lactate production is also increased in
septic shock, and many cancers also
produce lactate.