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Lecture

BIO CHEMISTRY

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9 views

Lecture

BIO CHEMISTRY

Uploaded by

dohaebada8
Copyright
© © All Rights Reserved
Available Formats
Download as PPTX, PDF, TXT or read online on Scribd
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Lecture(3)

CARBOHYDRATES METABOLISM
Cellular Respiration is an example of a metabolic pathway. Series
of chemical reactions take placed in cells. All the reactions involved
.in cellular respiration can be grouped into three main stages

,Glycolysis -1
,The Krebs cycle -2
.Electron transport chain & Oxidative phosphorylation -3
:GLYCOLYSIS
The Central Pathway of Glucose Degradation
Definition: Glycolysis means breakdown of glucose into pyruvate
and/or lactate, the process occurs in cell cytosol, it occurs in the
presence of oxygen and in its absence resulting in the conversion of
.glucose into pyruvate or lactate respectively
Site: cytoplasm of all tissue cells, but it is of physiological
importance in
Tissues with no mitochondria: RBCs, cornea, and .1
.lens
Tissues with few mitochondria: Testis, leucocytes, medulla .2
.of the kidney, retina, skin, and gastrointestinal tract
Tissues undergo frequent oxygen lack: skeletal muscles especially during .3
.exercise
:Stages of glycolysis
Stage (I) (the energy requiring stage): One molecule of glucose is
)converted into two molecules of glyceraldehyde-3-phosphate. b
.These steps require 2 molecules of ATP (energy loss)
: Stage (II) (the energy producing stage) .2
The 2 molecules of glyceraldehyde-3-phosphate are converted into
pyruvate (aerobic glycolysis) or lactate (anaerobic glycolysis b)
.These steps produce ATP molecules (energy production)
:Reactions of glycolytic pathway
The series of reactions of glycolytic pathway which degrades
.glucose to pyruvate are represented below
Stage (I): This is a preparatory phase. Before the glucose molecule
can be split, the rather asymmetric glucose molecule is converted to
almost symmetrical form, fructose 1,6-diphosphate by donation of
.two phosphate groups from ATP
Step (1): Phosphorylation of glucose in the cell and begins
.interring glycolysis (this step is spontaneous and irreversible)
This step is notable for two reasons: (1) glucose 6-phosphate
cannot diffuse through the membrane, because of its negative
charges, and (2) the addition of the phosphoryl group begins to
destabilize glucose, thus facilitating its further metabolism. The
transfer of the phosphoryl group from ATP to the hydroxyl group on
.carbon 6 of glucose is catalyzed by hexokinase or glucokinase
Glucose-6-P, intermediate forming an important branch point in
.metabolism
Step (2): The Formation of fructose 6-phosphate from
glucose 6-phosphate
-The next step in glycolysis is the isomerization of glucose 6
phosphate to fructose 6-phosphate, i.e., a conversion of an aldose
.into a ketose by phosphoglucose isomerase
Step (3): The Formation of fructose 1,6-bisphosphate from
fructose 6-phosphate
.A second phosphorylation reaction follows the isomerization step
-Fructose 6-phosphate is phosphorylated by ATP to fructose 1,6
.bisphosphate (F-1,6-BP), (this step is irreversible)

This reaction is catalyzed by phosphofructokinase (PFK), an


allosteric enzyme that plays a central role in the integration of much
.of metabolism
Step (4): The six-carbon sugar is cleaved into two three-carbon
fragments by aldolase
The second stage of glycolysis begins with the splitting of fructose
bisphosphate into glyceraldehyde 3-phosphate (GAP) and-1,6
dihydroxyacetone phosphate (DHAP). The products of the
remaining steps in glycolysis consist of three-carbon units rather
.than six-carbon units
This reaction is catalyzed by aldolase. This enzyme derives its
name from the nature of the reverse reaction, an aldol
condensation. The reaction catalyzed by aldolase is readily
reversible under intracellular conditions
Step (5): Dihydroxyacetone phosphate is isomerized to
glyceraldehyde-3-phosphate
,Glyceraldehyde 3-phosphate is on the direct pathway of glycolysis
whereas dihydroxyacetone phosphate is not. Unless a means exists
-to convert dihydroxyacetone phosphate into glyceraldehyde 3
phosphate, a three-carbon fragment useful for generating ATP will
be lost. These compounds are isomers that can be readily
interconverted: dihydroxyacetone phosphate is a ketose, whereas
.glyceraldehyde 3-phosphate is an aldose
The isomerization of these three-carbon phosphorylated sugars is
catalyzed by triose phosphate isomerase (TIM). This reaction is
.rapid and reversible
Stage (II)
It is the energy yielding stage. Reactions of this type in which an
aldehyde group is oxidized to an acid are accompanied by liberation
.of large amounts of potentially useful energy
-Step (6): Oxidation of glyceraldehyde 3-phosphate to 1,3
bisphosphoglycerate
The preceding steps in glycolysis have transformed one molecule of
glucose into two molecules of glyceraldehyde 3-phosphate, but no
energy has yet been extracted. On the contrary, thus for two
molecules of ATP have been invested. We come now to a series of
steps that harvest some of the energy contained in glyceraldehyde
phosphate. The initial reaction in this sequence is the conversion -3
-of glyceraldehyde 3-phosphate into 1,3-bisphosphoglycerate (1,3
BPG), a reaction catalyzed by glyceraldehyde 3-phosphate
.dehydrogenase
The oxidation of the aldehyde to an acid is coupled to the reduction
+ of NAD + to NADH/H

-Step (7): Conversion of 1,3-bisphosphoglycerate to 3


Phosphoglycerate
Keep in mind that, because of the actions of aldolase and triose
-phosphate isomerase, two molecules of glyceraldehyde 3
phosphate were formed and hence two molecules of ATP were
generated. These ATP molecules make up for the two molecules of
.ATP consumed in the first stage of glycolysis
Step (8): Conversion of 3-phosphoglycerate to 2-phosphoglycerate
The first reaction is a rearrangement. The position of the phosphoryl
-group shifts in the conversion of 3-phosphoglycerate into 2
phosphoglycerate, a reaction catalyzed by phosphoglycerate
.mutase
i.e., 3-Phosphoglycerate is isomerized to 2-phosphoglycerate. The
.phosphate ester is moved from carbon 3 to carbon 2
-Step 9: 2-Phosphoglycerate is dehydrated to form phosphoenol
pyruvate. The dehydration of the alcohol produces a double bond
between carbons 2 and 3 and creates a high-energy enol phosphate
.linkage
Step (10): Conversion of phosphoenolpyruvate to pyruvate
This reaction is catalyzed by the enzyme pyruvate kinase. The
hydrolysis of the phosphate from phosphoenolpyruvate is coupled to
the phosphorylation of ADP. The hydroxyl group that is produced
next to the carbon-carbon double-bond spontaneously isomerizes to
.a ketone
:Deregulation of Glycolysis in Cancer Cells
Glucose uptake and glycolysis is ten times faster in solid tumors
than in non-cancerous tissues. Tumor cells initially lack connection
to blood supply so limited oxygen supply. Tumor cells have fewer
mitochondrial, depend more on glycolysis for ATP. This lead to
.increase the levels of glycolytic enzymes in tumors cells
Biochemical Importance of Glycolysis
It is important energy source (8 ATPs) under aerobic condition or ●
under anaerobic condition. Mainly in contracting )2ATPs(
,muscles
.brain tissues and RBCs
It is the principal route for glucose oxidation and initiation of kreb's ●
.cycle via pyruvate and acetyl CoA
.It is the principal route for fructose and galactose metabolism ●
.It connects between the carbohydrates, lipid, and protein metabolism ●
.Its reversibility is in the process of gluconeogenesis ●
Glycolysis is the only energy source for RBCs and ending by lactate ●
formation due to the absence of mitochondria
Inhibition of glycolysis: Inhibitors are added to blood sample
before measurement of blood glucose level to prevent glycolysis
and false lower level of blood glucose. For example, Sodium
Fluoride is used when blood is collected for glucose estimations. In
the erythrocytes (RBC), it specifically inhibits the enzyme enolase of
the glycolytic pathway, preventing the consumption of glucose by
.the RBC’s if blood is left standing at room temperature

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