Lecture 1

Dr. Fatima Muccee

Assistant professor
School of Biochemistry and Biotechnology
University of the Punjab
Outline of the pathways for the
catabolism of carbohydrate, protein, and
fat. All these pathways lead to the
production of acetyl-CoA, which is
oxidized in the citric acid cycle, ultimately
yielding ATP by the process of oxidative
phosphorylation.
Carbohydrate metabolism
Digestion and absorption of
carbohydrates
Sites of digestion
Mouth & intestinal lumen

Final products of carbohydrate digestion

Glucose
Galactose
Fructose

Enzyme Glycoside hydrolases (glycosidases)

Hydrolysis of a glycosidic bond

Types of Glycoside hydrolases

Salivary α – amylase

Pancreatic α – amylase

Intestinal disaccharidases
 Salivary α – amylase
 α(1→4)- and β(1→4)-endoglucosidases in nature
 Human = no β(1→4)-endoglucosidases
 Acts on dietary starch and glycogen [α(1→4) & α(1→6)]
 Starch (amylose + amylopectin)
 Hydrolyze α(1→4) bonds of glycogen and starch
 Human = no cellulose digestion (as cellulose contains
β(1→4) linkages between glucose residues)
 Branched amylopectin and glycogen (α(1→6) bonds)
 Amylase = no hydrolysis of α(1→6) bonds
 Amylase on glycogen and amylopectin = a mixture of
short, branched and unbranched oligosaccharides known
as dextrins.
 Why carbohydrates don’t undergo
hydrolysis in stomach?

Carbohydrate digestion halts temporarily

in the stomach, because the high acidity
inactivates salivary α-amylase.
 Pancreatic α – amylase

 Digestion of starch

 Acid of stomach neutralized by pancreatic

bicarbonate
 Intestinal disaccharidases
 Final digestive processes
 Occur primarily at the mucosal lining of the upper
jejunum
 Isomaltase α(1→6) in isomaltose glucose
 Maltase α(1→4) bond in maltose and malto-
triose glucose
 Sucrase α(1→2) bond in sucrose

glucose and fructose

Lactase (β-galactosidase)

β(1→4) bond in lactose

galactose and glucose

Trehalase

α(1→1) trehalose
(disaccharide of glucose found in mushrooms
and other fungi)
 Intestinal enzymes

 Transmembrane proteins
 Brush border on the luminal surface of the intestinal
mucosal cells.
 Sucrase and isomaltase
Sucrose-isomaltase complex
Cleaved into two functional subunits
 Maltase = maltase glucoamylase protein (MGA)
Cleaves maltose and maltotriose
Glucoamylase activity = Cleaves α(1→4) glycosidic
bonds in dextrins
 Intestinal absorption of
monosaccharides
 Duodenum and upper jejunum

 Galactose and glucose

> Absorption in mucosal cells

> Active transport
> Transport protein = Sodium-dependent glucose

co-transporter 1 (SGLT-1)

> Counter-current uptake of sodium ions

 Fructose

> Facilitated diffusion

> Sodium-independent monosaccharide transporter

(GLUT-5)
Absorption by intestinal
mucosal cells of the
monosaccharide products of
carbohydrate digestion. SGLT-1
= sodium-dependent glucose
transporter.
 Mechanisms for glucose transport

A. Sodium-independent facilitated diffusion

transport system

B. Sodium–monosaccharide cotransport system

 A. Sodium-independent facilitated diffusion
transport system

> Family of 14 glucose transporter isoforms = GLUT-1 to GLUT-14

> Each transporter = two conformational states

> Monomeric proteins (single polypeptide chain)

> Binding with extracellular glucose = conformational change of

transporter
Schematic representation
of the facilitated transport
of glucose through a cell
membrane. [Note:
Glucose transporter
proteins are monomeric
and contain 12
transmembrane α helices.]
Tissue specificity of glucose transporter
gene expression
> GLUT-3 = Neurons

> GLUT-1 = Erythrocytes and the blood–brain barrier but is low in adult

muscle

> GLUT-4 = Muscle and adipose tissue

> GLUT-2 = Liver, kidney, and β cells of the pancreas

The number of GLUT-4 transporters active in these tissues is
increased by insulin.
 Specialized functions of glucose
transporter isoforms
> Facilitated diffusion
> Transporter mediated
> No energy
> Glucose uptake from blood = GLUT-1, GLUT-3 and GLUT-4
> GLUT-2 = Liver and kidney
High blood glucose = transport glucose from blood to cells
Low blood glucose = transport glucose from cells to blood
> GLUT-5 = Small intestine and testes
Transport fructose
 B. Sodium monosaccharide co-transport system

 Energy dependent

 Against conc. gradient

 Glucose transport coupled with conc. gradient of sodium ions

 Sodium dependent glucose transporter (SGLT)

 Epithelial cells of intestine, renal tubules and choroid plexus

Glycolysis
Fermentation
Glycolysis is regulated at three enzyme-
catalyzed reactions

Hexokinase

Phosphofructose kinase

Pyruvate kinase
Effect of insulin and glucagon on
the synthesis of key enzymes of
glycolysis in liver.

Gene transcription and

synthesis of glucokinase,
phosphofructokinase, and PK
are decreased when plasma
glucagon is high and insulin is
low (for example, as seen in
fasting or diabetes)
 Hexokinase

> Glucose 6-phosphate formation

> Hexokinase = feedback inhibition by product of reaction

> Phosphorylation of glucose is inhibited if there is a buildup of

glucose‐6‐ phosphate.

> This regulation reduces the rate of formation of glucose ‐6 ‐phosphate.

 Phosphofructose kinase

> Most important regulatory step of glycolysis is the phosphofructokinase

reaction.

> Allosteric enzyme

> Activated by fructose 6-bisphosphate, ADP, AMP and Pi.

> Inhibited by ATP, citrate and H+ ions.

 Pyruvate kinase
> Inhibited by ATP, acetyl-CoA and fatty acids

> Activated by fructose-1,6-bisphosphate