Carbohydrate

Metabolism
 Metabolism
Metabolism, which is the sum of all the chemical
changes occurring in a cell, a tissue, or the body.

Metabolism consists of catabolism and anabolism.

• Catabolism: degradative pathways, usually energy-

yielding!

• Anabolism: biosynthetic pathways, energy-requiring!

Figure (1): Showing three stages of catabolism.
Figure (2): Comparison of catabolic and anabolic
pathways
 Metabolism
 Catabolic pathways converge to a few end products.
 Anabolic pathways diverge to synthesize many
biomolecules.
 Some pathways serve both in catabolism and
anabolism.
 Such pathways are amphibolic.
• Catabolism is oxidative: substrates lose reducing
equivalents, usually H- ions.
• Anabolism is reductive: NADPH provides the
reducing power (electrons) for anabolic processes.
 Digestion of Carbohydrates
1- In mouth:
• Digestion of carbohydrates starts in the mouth by salivary α-amylase enzyme.
• This enzyme is produced by the salivary gland. Its optimum pH is 6.7 and it
is activated by chloride ion.
• salivary α-amylase acts on dietary starch and glycogen breaking some α-(1-
4) bonds to form a mixture of maltose and smaller branched oligosaccharide
molecules called starch dextrins (amylodextrin, erythrodextrin and
achrodextrin).
• Because both starch and glycogen also contain α-(1-6) bonds, the resulting
digest contains isomaltose.
• Because food remains for short time in the mouth, digestion of starch and
glycogen may be incomplete and gives a partial digestion. The digestion
product in the mouth gives maltose, isomaltose and starch dextrins.
 Digestion of Carbohydrates
2- In stomach:
• No digestion in the stomach for carbohydrate because of the
high acidity inactivates salivary α-amylase.
3- In small intestine:
- When the acidic contents of stomach reach the small
intestine, they are neutralized by bicarbonate secreted by
pancreas, and the pancreatic α-amylase continues the process
of starch digestion into maltose, isomaltose, sucrose and
lactose.
• The optimum pH for pancreatic α-amylase is 7.1
. Sucrase
Sucrose Glucose + Fructose
Lactase
Lactose Glucose + Galactose
Maltase
Maltose Glucose + Glucose
 Digestion of Carbohydrates

Digestion of Cellulose:
• The human body cannot produce β-(1-4) amylase so that they are
unable to digest cellulose β-(1-4) glucosidic linkage. So cellulose
passes as such in stool.
• Cellulose helps water retention during the passage of food along the
intestine producing larger and softer feces, so preventing constipation.
 Transport of glucose

•Glucose cannot diffuse directly into cells,

but enters by one of two transport
mechanisms:
• Na+-independent, facilitated diffusion
transport system
•or a Na+-monosaccharide cotransporter
system.
 Passive transport (facilitated diffusion) of
Monosaccharides
• This system is mediated by a family of 14 glucose transporters in cell
membranes. They are designated GLUT-1 to GLUT-14 (glucose
transporter isoforms 1-14).
• In facilitated diffusion, glucose movement follows a concentration
gradient, that is, from a high glucose concentration to a lower one. For
example, GLUT-1, GLUT -3, and GLUT-4 are primarily involved in
glucose uptake from the blood.
• In contrast, GLUT-2, which is found in the liver and kidney, can
either transport glucose into these cells when blood glucose levels are
high, or transport glucose from these cells when blood glucose levels
are low (for example, during fasting). GLUT-5 is unusual in that it is
the primary transporter for fructose (instead of glucose) in the small
intestine and the testes.
Na+-monosaccharide cotransporter system

• This is an energy-requiring process that transports glucose

―against‖ a concentration gradient—that is, from low glucose
concentrations outside the cell to higher concentrations
within the cell.
• This system is a carrier-mediated process in which the
movement of glucose is coupled to the concentration gradient
of Na+ , which is transported into the cell at the same time.
• The carrier is a sodium-dependent–glucose transporter or
SGLT. This type of transport occurs in the epithelial cells of
the intestine, renal tubules, and blood brain barrier
 Carrier protein
K+ +
Na

Na+ G

Cell membrane
ADP+Pi

ATPase
Sodium Na+ G
pump

ATP

K+

Cytoplasm
Na+ G

To capillaries
Mechanism of active transport of glucose
 Disorders of carbohydrate digestion

1- Lactose intolerance:
• This is a deficiency of lactase enzyme that hydrolyzes lactose into
glucose and galactose.
• Lactase deficiency may be congenital which develops soon after
birth or acquired which occurs later on life.
• The deficiency of lactase enzyme leads to accumulation of lactose in
small intestine which increased osmotic pressure, so water will be
drawn from the mucosa into the large intestine causing osmotic
diarrhea. Moreover, bacterial fermentation action on lactose leads to
formation of carbon dioxide which causes flatulence and abdominal
cramps.
• Treatment simply removes lactose from diet.
 Disorders of carbohydrate digestion

2- Sucrase deficiency:
•This is an inherited deficiency of the sucrase.
• Symptoms are the same as those described in
lactase deficiency.
Fate of absorbed sugars
 Overview of glycolysis

The Embden-Meyerhof Pathway

 Essentially all cells (cytosol) carry out
glycolysis (break down of glucose & producing
small amount of energy).
 Ten reactions; same in all cells but differ in
rates.
Two phases:
 First phase (energy investment phase)
 Second phase produces (energy generation phase)
 Products are pyruvate, ATP and NADH
 Three possible fates for pyruvate
 Reactions of glycolysis

(1) Phosphorylation of glucose: Glu Glu-6-p

by (hexokinase, found in all cells or glucokinase
, in the liver & β-cells of pancreas), irreversible
step, (to trap Glu), rate limiting step.
 Glucose-6-phosphate:

Glucose-6-phosphate cannot easily cross plasma

membrane.
 Points of comparison Glucokinase Hexokinase

Tissue distribution Liver and β-cells of pancreas Most tissues

Substrate specificity Acts on glucose only Acts on glucose, fructose and galactose.

Km and Vmax Have high Km and high Vmax (low Have low Km and low Vmax (high affinity for
affinity for glucose) glucose)

Inhibition by glucose-6- Not inhibited by reaction product. Inhibited by reaction product.

phosphate

Carbohydrate diet on activity Affected by fasting or by high Not affected by fasting or by high
carbohydrate diet carbohydrate diet

Insulin hormone Its synthesis is induced by insulin Not induced by insulin.

Diabetes mellitus Decreased in diabetes M. No change in diabetes M.

 Reactions of glycolysis
(2)Isomerization of Glu-6-p: Glu-6-pFru-6-p by
phosphoglucose isomerase, reversible step.
(3) Phosphorylation of Fru-6-P: Fru-6-P Fru-1,6-bisP
by phosphofructokinase-1 (PFK-1), irreversible step,
rate limiting step.
(4) Cleavage of Fru-1,6-bisP: by aldolase A to dihydroxy-
acetone phosphate and glyceraldhyde-3-phosphate,
reversible step.
(5) Isomerization of dihydroxy-acetone phosphate: by
triose phosphate isomerase, interconvert of dihydroxy-
acetone phosphate to glyceraldhyde-3-phosphate, the
result is 2 molecule of glyceraldhyde-3-phosphate.
 Reactions of glycolysis
(6) Oxidation of glyceraldhyde-3-phosphate: to
1,3 bisphosphoglycerate (1,3 BPG) by
glyceraldhyde-3-phosphate dehydrogenase.

(7) Formation of ATP from 1,3 BPG and ADP: 1,3

BPG is high energy phosphate group used in
synthesis of ATP in a reaction catalyzed by
phosphoglycerate kinase. In this reaction 2 ATP is
formed and 3 -PG. (ATP synthesis from a high-
energy phosphate known as substrate-level
phosphorylation)
 Reactions of glycolysis
(8) Shift of the phosphate group from C-3 to C-2:
reversible reaction, by mutase to form 2-PG.

(9) Dehydration of 2 PG: by enolase to form

phosphoenolpyruvate (PEP) which is high energy
phosphate group.
 Reactions of glycolysis
(10) Formation of pyruvate: (substrate level
phosphorylation), PEP  Pyruvate (end product
of aerobic glycolysis) by pyruvate kinase,
irreversible reaction.

(11) Reduction of Pyruvate to lactate: by lactate

dehydrogenase, it is the end product of anaerobic
glycolysis.
 Energy yield of glycolysis
Reaction ATP (+ or -)

1- Hexokinase / Glucokinase - one ATP

2- PFK-1 - one ATP

3-Glyceraldehyde-3-P dehydrogenase (aerobic) + 2 NADH+H+ × 3 = + 6 ATP

4- Phosphoglycerate kinase + 2 × 1 = + 2 ATP

5- Pyryvate Kinase + 2 × 1 = + 2 ATP

Total aerobic glycolysis + 8 ATP

Total anaerobic glycolysis + 2 ATP

Figure (3): Two phases of aerobic glycolysis
 Glycolysis in RBCs

• RBCs. contain no mitochondria, thus:

• They depend only upon glycolysis for energy
production (= 2ATP).
• Even under aerobic condition, glycolysis terminates
in lactate due to the enzymatic machinery of
pyruvate oxidation is not present in RBCs. (due to
absence of mitochondria).
Synthesis of 2,3 bisphosphoglycerate in
red blood cells.
 Synthesis of 2,3 bisphosphoglycerate in
red blood cells.
 Some of 1,3 bisphosphoglycerate is converted to 2,3 bisphosphoglycerate (2,3
BPG) by action of bisphosphoglycerate mutase.
 2,3 bisphosphoglycerate found in trace amount in most cells but at high
concentration in the red blood cells (increases Oxygen delivery).
The concentration of 2,3-BPG in the RBC increases in response to chronic
hypoxia, such as that observed in chronic obstructive pulmonary disease
(COPD), or at high altitudes, Intracellular levels of 2,3-BPG are also elevated
in chronic anemia. Elevated 2,3-BPG levels lower the oxygen affinity of
hemoglobin, permitting greater unloading of oxygen in the capillaries of the
tissue
 2,3 bisphosphoglycerate is hydrolyzed by phosphatase to 3 phosphoglycerate
(an intermediate of glycolysis).