DIGESTION, ABSORPTION & TRANSPORT

OF CARBOHYDRATES
MAJOR DIETARY CARBOHYDRATES
 DIGESTION & ABSORPTION OF CHO
DIGESTION
Monosaccharides Glucose, Galactose, Fructose
- no hydrolysis prior to absorption

Disaccharides - Sucrose, Maltose, Lactose

-breakdown into monosaccharides intestinal

surface enzymes (disaccharidases).

Polysaccharides - Starch, Glycogen, Oligomers
Mouth : salivary amylase ( 1,4 glycosidase or
endoglycosidase)
mucin, a gl;ycoprotein for lubrication and
dispersion of CHO.
STARCH Maltose + Isomaltose + Limit Dextrin
Small Intestine:
exocrine pancreatic secretions
- contain bicarbonate
- pancreatic amylase (1,4 glycosidase)
- disaccharides and dextrins
intestinal surface enzymes : brush border
membrane of the absorptive cells in the
intestinal villi.
- Sucrase-Isomaltase complex
- Glucoamylase complex ( exoglucosidase -
acts on 1,4 glycosidic bonds at the non-
reducing ends)
Sucrase-Isomaltase Complex
- B-Glycosidase complex (Lactase)
INTESTINAL
SURFACE
ENZYMES
ACTION OF SALIVARY AND PANCREATIC AMYLASE
ABSORPTION
Two Types of Glucose Transport Proteins in the Intestinal Absorptive cells.
Na+ - dependent monosaccharide transporter ( active symport )
- specific for glucose and galactose
Facilitative monosaccharide transporter ( no energy expenditure)
- more specific for fructose than glucose.
 TRANSPORT OF MONOSACCHARIDES INTO TISSUES

GLUT 1 : RBC, Blood brain barrier, kidney ,colon and other cells
Specilized to provide steady flow of glucose
GLUT 2: Liver, B cells of pancreas , kidney
Requires high [glucose] for half saturation; high Km
GLUT 3: Neuronal cells of the Brain
Higher affinity for glucose than GLUT 1 ; low Km
GLUT 4: Major transporter in the muscle and adipocytes (
Insulin dependent
GLUT 5: Small Intestines and kidney
Fructose transport
 GLYCOLYSIS

EMBDEN MEYERHOF PATHWAY

 GLYCOLYSIS

Preparatory or Priming

Phase

ENZYMES;

1. HEXOKINASE

2. PHOSPHOGLUCOSE ISOMERASE

3. PHOSPHOFRUCTOKINASE 1

4. ALDOLASE

5.. TRIOSE PHOSPHATE ISOMERASE

 GLYCOLYSIS
PAYOFF PHASE

ENZYMES:

6. GLYCERALDEHYDE-3-PO4

DEHYDROGENASE

7. PHOSPHOGLYCERATE KINASE

8. PHOSPHOGLYCEROMUTASE

9. ENOLASE

10. PYRUVATE KINASE

GLUCOSE OVERVIEW OF GLYCOLYSIS
ATP

GLUCOSE-6-PO
ADP 4

FRUCTOSE-6-PO4
ATP

ADP
FRUCTOSE-1,6 - bisPO4

DIHYDROXY ACETONE GLYCERALDEHYDE-3-PO4

PHOSPHATE NAD + PI

1,3 DIPHOSPHOGLYCERATE
NADH
ADP

3-PHOSPHOGLYCERATE
ATP

2-PHOSPHOGLYCERATE
ATP ADP

PYRUVATE PHOSPHOENOLPYRUVATE
 FATE OF PYRUVATE
AEROBIC GLYCOLYSIS

CH3 NAD+ NADH + H CH3

C = O C = O

COO- PYR. DEHYDROGENASE S - CoA

Pyruvate Acetyl-CoA
ANAEROBIC GLYCOLYSIS

CH3 NADH NAD+ CH3

C = O H- C-OH

COO- LACTATE DEHYDROGENASE COO-

 FATE OF NADH FROM GLYCOLYSIS

AEROBIC GLYCOLYSIS

- REDUCING EQUIVALENTS ARE SHUTTLED INTO THE MITOCHONDRIA

- TWO SHUTTLE SYSTEMS

GLYCEROPHOSPHATE SHUTTLE = 2 ATPs

(skeletal muscle and brain mitocondria )

ANAEROBIC GLYCOLYSIS
MALATE-ASPARTATE SHUTTLE = 3 ATPs

- NADH is used by lactate

( liver, kidney,deydrogenase
heart mitochondria)

NADH NAD+
ENERGETICS OF GLYCOLYSIS

ANAEROBIC GLYCOLYSIS No. of ATP

. Glucose 2 Pyruvate 2 Lactate

Substrate level phosphorylation 4

Number of ATP used -2

AEROBIC GLYCOLYSIS

1. Glucose 2 Pyruvate NET 2 ATPs

Substrate level phosphorylation 4

2 NADH produced ( via Malate-Aspartate Schuttle X 3 ATP /NADH ) 6

( via glycerophosphate Shuttle X 2 ATP/ NADH )

2. 2 Pyruvate 2 Acetyl CoA

2 NADH produced X 3 ATP / NADH 6

3. 2 ( Acetyl CoA CO2 + H2O )

3 NADH X 3ATP / NADH 9 ATP

1 FADH2 X 2 ATP / FADH2 2 ATP

 GLUCOSE REGULATION OF GLYCOLYSIS

HEXOKINASE (GLUCOKINASE - Liver)

ATP

- broad specificity for hexoses (glucose only)

- low Km ( high Km )
GLUCOSE-6-PO4
PHOSPHOFRUCTOKINASE or PFK -1
- Feedback (product) inhibition ( - )

- Rate limiting step

FRUCTOSE-PO4

- Allosteric activators : AMP, ADP

ATP
Fructose 2,6 bisphosphate
PYRUVATE KINASE or PK

- Allosteric inhibitors : ATP, Citrate

- Feedforward activation: Fructose 1,6-bis
FRUCTOSE- 1,6- bis PO4
phosphate
NADH
-Inhibitors: ATP. Acetyl CoA, Alanine &

Phenylalamine
 IMPORTANCE OF GLYCOLYSIS

SKELETAL MUSCLE - anaerobic glycolysis

provides ATP when aerobic oxidation

becomes insufficient
HEART MUSCLE - during conditions of ischemia

poor glycolytic activity --- less ATP

BRAIN & RED BLOOD CELLS - Glucose

is the major source of fuel.

SOURCE OF IMPORTANT METABOLITES

ex. Glycerol backbone of fats (adipocytes)

2,3 DPG ( RBC)

 GLUCONEOGENESIS

SYNTHESIS OF GLUCOSE FROM

NONCARBOHYDRATE SOURCES
 GLUCONEOGENESIS

PROVIDES THE BODY WITH GLUCOSE WHEN CARBOHYDRATE IS NOT

AVAILABLE FROM THE DIET. ( ie. fasting, starvation, diabetes)

FOUND IN THE LIVER AND KIDNEY

ITS SUBSTRATES ARE GLUCOGENIC AMINO ACIDS, LACTATE , GLYCEROL,

PROPIONATE AND INTERMEDIATES OF THE TCA CYCLE..

OVERALL REACTION OF GLUCONEOGENESIS

ACTIVATED BY GLUCAGON IN RESPONSE TO HYPOGLYCEMIA.

+
2 PYRUVATE + 4 ATP + 2GTP + 2NADH + 2H + H2O

+
GLUCOSE + 2NAD + 4ADP + 2 GDP + 6Pi
 GLUCOSE

ATP

G G
1.

L
L GLUCOSE-6-PO4
U

Y FRUCTOSE-6-PO4
C

ATP O
C
2. N

O FRUCTOSE- 1,6- bis PO4 E

NADH O
OXALOACETATE (2)
L
G

Y ATP E
 GLUCOSE
GLUCONEOGENESIS
ATP

1.
OXALOACETATE
GLUCOSE-6-PO4

CO2
MALATE

FRUCTOSE-6-PO4 GTP

ATP MALATE

2. NADH

OXALOACETATE
FRUCTOSE- 1,6- bis PO4
CO2

NADH ATP

PYRUVATE
 THERMODYNAMIC BARRIERS PREVENT A SIMPLE REVERSAL OF

GLYCOLYSIS

THREE BY-PASS REACTIONS IN GLUCONEOGENESIS

PYRUVATE + CO2 + ATP OXALOACETATE + ADP + P

PYRUVATE CARBOXYLASE

OXALOACETATE + GTP PHOSPHOENOLPYRUVATE + GDP + PI

FRUCTOSE-1,6-bisPHOSPHATE + H20 FRUCTOSE-6-PHOSPHATE + Pi

PEP CARBOXYKINASE

FRUCTOSE-1,6-bisPHOSPHATASE

GLUCOSE-6-PHOSPHATE + H2O GLUCOSE + PI

GLUCOSE-6-PHOSPHATASE (liver)
 COVALENT MODIFICATION BY
GLYCOLYSIS & GLUCONEOGENESIS
REVERSIBLE PHOSPHORYLATION
SHARE THE SAME PATHWAY BUT IN

GLUCAGON (Epinephrine) inhibits

OPPOSITE DIRECTIONS, THEY MUST
glycolysis and stimulate gluconeogenesis
BE REGULATED RECIPROCALLY.
THREE TYPES OF MECHANISMS: by increasing the [cAMP].This in turn

INDUCTION / REPRESSION OF activates cAMP-dependent protein kinase

ENZYME SYNTHESIS. phosphorylation and inactivation of

ALLOSTERIC MODIFICATION
Pyruvate Kinase.
Insulin enhances the synthesis of
Pyruvate Carboxylase - Acetyl CoA
the key enzymes of glycolysis and
(Allosteric activator) lowers Km for the
antagonizes the effect of the
bicarbonate.
glucocortecoids and glucagon-

stimulated cAMP, which induce the Fructose-1,6-bisPhosphatase, - Fru-1,6

HEXOSE MONOPHOSPHATE SHUNT

PENTOSE PHOSPHATE PATHWAY

THE CORI CYCLE
HEXOSE MONOPHOSPHATE SHUNT or HMP SHUNT

MAJOR FUNCTIONS:
To provide NADPH for reductive biosynthesis

( ie. Fatty acid and cholesterol synthesis)

To provide PENTOSES, HEXOSES also trioses and tetroses, etc.

ACTIVE IN THE FOLLOWING TISSUES: liver, adipose tissues,

(ie. RIBOSE for nucleotides and nucleic acids)

lactating mammary glands, RBC, adrenal cortex, thyroid and testis.

SUMMARY OF PATHWAY

+
3 GLUCOSE-6-PO4 + 6 NADP 2 GLUCOSE-6-PO4 + 3 CO2

+
+ GLYCERALDEHYDE-3-PO4 + 6 NADPH + 6H
PENTOSE PHOSPHATE PATHWAY
 GLUCOSE-6-PHOSPHATE
O
NADP+ THE PENTOSE PHOSPHATE
XI
NADPH
D
H2O PATHWAY
A
6-PHOSPHOGLUCONOLACTONE
TI
NADP+
CO2
V
NADPH
E 6-PHOSPHOGLUCONATE
N

O
TK

O RIBULOSE-5-PHOSPHATE TA

I TK
XYLULOSE-5-PHOSPHATE + RIBOSE-5-PHOSPHATE
D

A
 IMPORTANCE OF HMP SHUNT

IN THE ERYTHROCYTES: - regeneration of reduced Glutathione

+
G-S-S-G (ox) + NADPH + H 2 G-SH (red) + H2O

Glutathione reductase

- PROTECT THE CELLS FROM THE DESTRUCTIVE EFFECT OF H2O2

- GLUCOSE-6-PHOSPHATE
PREVENTS THE FORMATION OF METHEMOGLOBIN (Fe-III ) WHICH IS INACTIVE IN
DEHYDROGENASE DEFICIENCY - LEADS

CARRYING OXYGEN
HEMOLYTIC ANEMIA

THIAMINE DEFICIENCY CAN AFFECT THE TRANSKETOLASE

ACTIVITY.
 GLYCOGEN METABOLISM

GLYCOGENESIS : GLYCOGEN SYNTHESIS

GLYCOGENOLYSIS : GLYCOGEN DEGRADATION

THE GLYCOGEN STRUCTURE
TISSUE DISTRIBUTION OF CHO ENERGY RESERVES

TISSUE TYPE AMOUNT %TISSUE MASS CALORIES

Liver Glycogen 75 g 3 - 5% 300

Muscle Glycogen 250 g 0.5 - 1.0 % 1000

Blood & isGlucose

( Glycogen 10 g as glycogen
found in the cytoplasm - granules) 40
FUNCTIONS OF GLYCOGEN IN THE LIVER AND THE

SKELETAL MUSCLES.
IN THE LIVER

- THE GLYCOGEN STORES ARE A RAPIDLY REBUILT AND DEGRADED

STORE OF GLUCOSE - EVER RESPONSIVE TO SMALL AND RAPID

CHANGES IN BLOOD GLUCOSE LEVELS.

- FIRST LINE OF DEFENSE AGAINST DECLINING BLOOD GLUCOSE

CONCENTRATION ( HYPOGLYCEMIA).

IN THE MUSCLES
- IN RESPONSE TO STRESS ( fight or flight) HORMONES,

EPINEPHRINE,
- GLYCOGEN ISAND NOREPINEPHRINE,
AN IMPORTANT THE LIVER
FUEL SOURCE STIMULATES
WHEN THE ATP DEMANDS
GLYCOGENOLYSIS
 GLYCOGENOLYSIS

GLYCOGEN (n) + Pi GLUCOSE-1-PO4 +

PHOSPHORYLASE GLYCOGEN (n-1)

GLUCOSE-1-PO4 GLUCOSE-6-PO4
PHOSPHOGLUCOMUTASE
(LIVER)
GLUCOSE-6-PO4 + H2O GLUCOSE + Pi

GLUCOSE-6-PHOSPHATASE

EGLUCOSE [ GLUT 2 ] GLUCOSE

membrane (Blood)

Debranching enzyme:

Transglycosylase - moves short segment ofglucose residues bound to 1-6 to an adjacent 1-4

chain.
 GLYCOGENESIS

ATP + GLUCOSE GLUCOSE-6-PO4 + ADP

hexokinase

GLUCOSE-6-PO4 GLUCOSE-1-PO4

phospoglucomutase

GLUCOSE-1-PO4 + UTP UDP-GLUCOSE + PPi

Glu-1-PO4 uridyl transferase

UDP-GLUCOSE + GLYCOGEN (n) UDP + GLYCOGEN(n+1)

glycogen synthetase
GLYCOGENESIS

UDP-GLU UDP

core core
Glycogen

synthetase
6 UDP-GLU
Glycogen

6 UDP synthetase

core
core
4,6,transferase (branching enzyme)
 ENERGETICS OF GLYCOGENESIS

GLUCOSE-6-PO4 GLUCOSE-1-PO4

GLUCOSE-1-PO4 + UTP UDP-GLUCOSE + PPi

PPi + H2O 2 Pi

UDP-GLUCOSE + GLYCOGEN (n) GLYCOGEN(n+1) + UDP

NET:

UDP + ATP UTP + ADP

GLUCOSE-6-PO4 + ATP GLYCOGEN(n) + H2O

GLYCOGEN(n+1) + ADP + 2 Pi
STORAGE OF ONE GLUCOSE CONSUMES ONE ATP
MOBILIZATION OF HEPATIC GLYCOGEN BY GLUCAGON
ACTIVATION OF HEPATIC GLYCOGENOLYSIS BY EPINEPHRINE
THE END