Presentation 1 of Physiology.pptx

Submitted To: Madam Sidra Yaseen
Submitted By: Group 4
Subject : Physiology
Department : Pharmacy
The University of Lahore

Name Registration no.
Iman Asif 70147105
Abram Imran
Ayman Fayaz
m. Ubaid Ur Rehman
Sonia zaman
Uzair Ashraf
Hammad Ashraf
Aliza Saleem
M. Bilal Rana
Areeb Fatima
Aliza Shehzadi
Group 4 Members

Metabolism of Carbohydrates
Introduction to metabolism
“Metabolism is the sum of chemical processes that make it possible for the cells to
continue living.”
Release of Energy from Foods
 Many of the chemical reactions in the cells are aimed at making the energy in foods
available to the various physiological systems of the cell.
 For instance, energy is required for muscle activity, secretion by the glands, synthesis
of substances in the cells, and many other functions.

Coupled Reactions
 All the energy foods—carbohydrates, fats, and proteins—can be oxidized in the
cells, and during this process, large amounts of energy are released.
 These same foods can also be burned with pure oxygen outside the body in an actual
fire, also releasing large amounts of energy; in this case, however, the energy is
released suddenly, all in the form of heat.
 The energy needed by the physiologic processes of the cells is not heat.
 Our body require energy in the form of ATP.
 To provide this energy, the chemical reactions must be “coupled” with the systems
responsible for these physiologic functions.

Free energy
 The amount of energy liberated by complete oxidation of a food is
called the free energy.
 It is generally represented by the symbol ΔG.
 It is usually expressed in terms of calories per mole of substance.
 For instance, the amount of free energy liberated by complete
oxidation of 1 mole (180 grams) of glucose is 686,000 calories.

Adenosine Triphosphate (ATP) is “Energy Currency” Of Body
ATP is an essential link between energy-utilizing and energy-producing functions of body.
ATP is central link between energy-
producing & energy-utilizing systems of
Body. ADP, adenosine Diphosphate ; Pi,
Inorganic Phosphate

Energy Derived
Energy derived from oxidation of carbohydrates , proteins and fats which is used to convert
ADP to ATP which is then consumed by various reactions of body that are necessary for :-
1. Active Transport of molecules across Cell Membrane
2. Contraction of Muscles and performance of mechanical work
3. Conduction of Nerve Impulses
4. Cell Division and Growth
5. Other Physiological Functions (Metabolism & Reproduction)

Structure Of ATP
ATP is chemical Compound that is present in all cells . ATP is combination of
adenine , ribose and three phosphate radicals .
The last Two phosphate radicals are connected with the remainder of the molecule by
high-energy bonds , which are indicated by the symbol ~

Amount of Free Energy
In Each of these high-energy bonds per mole of ATP is about :
• 7300 Calories ➡️ under standard conditions
• 12,000 Calories ➡️ under usual conditions of temperature & concentration of reactants in
body.
From ATP
• After loss of one Phosphate Radical  Becomes ADP
•After loss of second Phosphate Radical Becomes AMP

Principal Purpose of This Chapter
 How the energy from carbohydrates can be used to form ATP in the cells
 Normally 90% or more of all the carbohydrates utilized by the body are for
this purpose .

Central role of gulcose and carbohydrate of metabolism
 Glucose cannot easily diffuse through the pores of the cell membrane.
 Maximum molecular weight of particles that can diffuse readily is about 100,
 glucose has a molecular weight of 180.
 glucose does pass to the interior of the cells with a reasonable degree of freedom by the
mechanism of facilitated diffusion.
 If the concentration of glucose is greater on one side of the membrane than on the other
side.
 Glucose will be transported from the high-concentration area to the lower concentration
area than in the opposite direction.

Transport Of Glucose Through Cell Membrane
 The final products of carbohydrate digestion areglucose, fructose, and galactose.
 Absorption from the intestinal tract, much of the fructose
 And almost all the galactose are rapidly converted into glucose in the liver.
 Therefore, little fructose and galactose are present in the circulating blood.
 Therefore, glucose-6-phosphate can be degraded to glucose and phosphate, and the
glucose.
 When the liver releases the monosaccharides back into the blood, the final product is
almost entirely glucose.

Insulin Decrease In Facilitated Diffusion
 The rate of glucose transport, as well as transport of some other monosaccharides, is
greatly increased by insulin.
 Large amounts of insulin are secreted by the pancreas.
 The rate of glucose transport into most cells increases to 10 or more times the rate of
transport when no insulin is secreted.
 Amounts of glucose that can diffuse to the insides of most cells of the body in the absence
of insulin.with the exception of liver and brain cells. far too little to supply the amount of
glucose normally required for energy metabolism.
 In effect, the rate of carbohydrate utilization by most cells is controlled by the rate of
insulin secretion.

Phosphorylation Of Glucose
●Glucose enters the cell and combines with phosphate radical.
 Phosphorylation is prompted mainly by the enzyme glucokinase (in
liver) and by hexokinase (in other cells).
 Mostly, phosphorylation of glucose is irreversible.
 But reversible in some cells (liver cells, renal tubular, and interstitial
epithelial cells) due to another enzyme, glucose phosphatase.
 It can reverse the action.

 In most tissues, phosphorylation serves to capture glucose in the cell.
 That is, because of its instantaneous binding with phosphate, the glucose
will not diffuse back out, except from those special cells.

Glycogen is stored in Liver & Muscle
 After absorption into a cell, glucose can be used immediately for the
release of energy to the cell.
 Glucose can be stored in the form of glycogen.
 All cells of the body are capable of storing at least some glycogen.
 Liver cells & muscle cells can store glycogen up to 8% & 3% of their
weight, respectively.
 The glycogen molecule can be polarized to any molecular weight.
 Most of the glycogen precipitates in the form of solid granules.

• This conversion of glucose to glycogen allows for a large amount of
carbohydrates to be stored without altering intracellular fluid
osmotic pressure, unlike low-molecular weight soluble
monosaccharides.
• High concentration of low molecular weight soluble
monosaccharides would play havoc with the osmotic relations
between intracellular and extracellular fluids.

Glycogenolysis
 Glycogenolysis means break down of glucose
 Glycogen is converted into glucose by the help of phosphorylase enzyme which is activated by
two following hormones
1)Epinephrine
• Initial effect of hormone is the formation of cyclic AMP in the cells to activate phosphorylase.
• When the sympathetic nervous system Is stimulated ,it increase the availability of glucose for
rapid energy metabolism
2) Glucagon
• when the concentration of glucose falls too low in body ,this hormone is secreted by the alpha
cells of pancreas.
• stimulation of formation of cyclic AMP occur which promotes the conversion of liver
glycogen to glucose and release in blood.
• In this way blood glucose concentration become rise in the body.

Release of Energy from Glucose by the Glycolytic Pathway:
 Because complete oxidation of 1 gram-mole of glucose releases 686,000 calories of
energy and only 12,000 calories of energy are required to form 1 gram-mole of ATP,
energy would be wasted if glucose were decomposed all at once into water and carbon
dioxide while forming only a single ATP molecule.
 Fortunately, cells of the body contain special enzymes that cause the glucose molecule
to split a little at a time in many successive steps, so that its energy is released in small
packets to form one molecule of ATP at a time, thus forming a total of 38 moles of ATP
for each mole of glucose metabolized by the cells.

Glycolysis
 Glycolysis means splitting of the glucose molecule to form two molecules of pyruvic
acid.
 Glycolysis occurs by 10 successive chemical reactions.
 Each step is catalyzed by at least one specific protein enzyme.
 Note that glucose is first converted into fructose-1,6 diphosphate and then split into
two three-carbon-atom molecules, glyceraldehyde-3-phosphate, each of which is then
converted through five additional steps into pyruvic acid.

Formation of ATP during Glycolysis
 Despite the many chemical reactions in the glycolytic series, only a small portion of the
free energy in the glucose molecule is released at most steps.
 However, between the 1, 3-diphosphoglyceric acid and the 3-phosphoglyceric acid stages,
the packets of energy released are greater than 12,000 calories per mole.
 Thus, a total of 4 moles of ATP are formed for each mole of fructose-1, 6-diphosphate that
is split into pyruvic acid.
 Yet, 2 moles of ATP are required to phosphorylate the original glucose to form fructose-1,
6-diphosphate before glycolysis could begin.
 Therefore, the net gain in ATP molecules by the entire glycolytic process is only 2 moles
for each mole of glucose utilized. This amounts to 24,000 calories of energy that becomes
transferred to ATP.

Conversion of Pyruvic Acid to Acetyl Coenzyme A
 The next stage is the conversion of the two pyruvic acid molecules into two
molecules of acetyl coenzyme A (acetyl CoA), in accordance with the
following reaction:

 Coenzyme A is a derivative of the vitamin pantothenic acid.
 In this conversion, no ATP is formed, but up to six molecules of ATP are formed
when the four released hydrogen atoms are later oxidized.
Conversion of Pyruvic Acid to Acetyl Coenzyme A

Citric Acid Cycle (Krebs cycle)
 The next stage in the degradation of the glucose molecule is called the citric acid
cycle.
 It is also called the tricarboxylic acid cycle (TCA cycle) or the Krebs cycle in honor
of Hans Krebs for his discovery of this cycle.
 These reactions all occur in the matrix of mitochondria.
 The citric acid cycle is a sequence of chemical reactions in which the acetyl portion
of acetyl-CoA is degraded to carbon dioxide and hydrogen atoms.
 The released hydrogen atoms add to the number of these atoms that will subsequently
be oxidized releasing tremendous amounts of energy to form ATP.

Citric Acid Cycle (Krebs
cycle)

The above figure shows the different stages of the chemical reactions in the citric acid cycle.
The substances to the left are added during the chemical reactions, and the products of the chemical
reactions are shown to the right.
Note at the top of the column that the cycle begins with oxaloacetic acid, and at the bottom of the
chain of reactions, oxaloacetic acid is formed again.
Thus, the cycle can continue repeatedly.
In the initial stage of the citric acid cycle, acetyl-CoA combines with oxaloacetic acid to form citric
acid.
The coenzyme A portion of the acetyl-CoA is released and can be used repeatedly for the formation
of still more quantities of acetyl-CoA from pyruvic acid.
The acetyl portion, however, becomes an integral part of the citric acid molecule.
During the successive stages of the citric acid cycle, several molecules of water are added, as shown
on the left and carbon dioxide and hydrogen atoms are released at other stages in the cycle, as shown
on the right in the figure.

 The net results of the entire citric acid cycle are provided below
 Two molecules of ATP are formed, as follows.
Formation of ATP in the Citric Acid Cycle
 The citric acid cycle itself does not cause a great amount of energy to be released; a
molecule of ATP is formed in only one of the chemical reactions—during the change
from α-ketoglutaric acid to succinic acid.
 Thus, for each molecule of glucose metabolized, two acetyl-CoA molecules pass
through the citric acid cycle, each forming a molecule of ATP, or a total of two
molecules of ATP formed.
Citric Acid Cycle (Krebs cycle)

 As already noted at several points in this discussion, hydrogen atoms are released
during different chemical reactions of the citric acid cycle—4 hydrogen atoms during
glycolysis, 4 during formation of acetyl-CoA from pyruvic acid, and 16 in the citric
acid cycle; thus a total of 24 hydrogen atoms are released for each original molecule
of glucose.
 However, the hydrogen atoms are not simply turned loose in the intracellular fluid.
 Instead, they are released in packets of two, and in each instance, the release is
catalyzed by a specific protein enzyme called a dehydrogenase.
Function of Dehydrogenases and Nicotinamide Adenine
Dinucleotide in Causing Release of Hydrogen Atoms in the
Citric Acid Cycle

Twenty of the 24 hydrogen atoms immediately combine with nicotinamide adenine
dinucleotide (NAD+), a derivative of the vitamin niacin, in accordance with the
following reaction:
Dinucleotide in Causing Release of Hydrogen Atoms in the
Citric Acid Cycle

 This reaction will not occur without intermediation of the specific dehydrogenase or
without the availability of NAD+ to act as a hydrogen carrier.
 Both the free hydrogen ion and the hydrogen bound with NAD+ subsequently enter
into multiple oxidative chemical reactions that form large quantities of ATP.
 The remaining four hydrogen atoms released during the breakdown of glucose—the
four released during the citric acid cycle between the succinic and fumaric acid
stages—combine with a specific dehydrogenase but are not subsequently released
to NAD+.
 Instead, they pass directly from the dehydrogenase into the oxidative process.
Dinucleotide in Causing Release of Hydrogen Atoms in
the Citric Acid Cycle

Function of Decarboxylases in Causing Release of Carbon
Dioxide
 Referring again to the chemical reactions of the citric acid cycle, as well as to
those for the formation of acetyl-CoA from pyruvic acid, we find that there are
three stages in which carbon dioxide is released.
 To cause the release of carbon dioxide, other specific protein enzymes, called
decarboxylases, split the carbon dioxide away from the substrate.
 The carbon dioxide is then dissolved in the body fluids and transported to the
lungs, where it is expired from the body.

Formation of large quantities of ATP by oxidation of Hydrogen-The process of oxidative
Phosphorylation
• Two molecules formation Glycolysis
• Two molecules formation Citric Acid cycle
• But 90% ATP formed during oxidation of H2
• Function of early stages (Glycolysis and Citric acid cycle etc.)
Making Hydrogen available for oxidation
• Each H2 atom
H+ ion
e- This e- combine with O2 and H2O to form OH-
• Then this OH- combine with the hydrogen to form H2O
• During this reaction energy is released to form ATP which is called oxidative
Phosphorylation and mechanism is called chemiosmotic mechanism.

Chemiosmotic Mechanism
 The released Hydrogen are always in pairs .
 One combine with NAD+ to form NADH
 Others H+ ion
 e- released enter into ETC
 Several components of ETC (Flavoprotein , Iron Sulphide protein , ubiquinone , cytochrome B
, Cl , C, A3)
 Finally e- reached to cytochrome A3 which is called cytochrome oxidase because it can give 2
electron and 2 e- ion which can reduce elemental oxygen to form ionic oxygen which combine
with H2 ion to form H2O.
 During this energy released which causes synthesis of ATP.
 Now energy is synthesis in the form of ADP (H+ ion combine with it and form ATP).
 This ATP then is transfer across the membrane with the knobe like structure( F1 and FO
particles )

Mitochondrial Chemiosmotic mechanism of oxidative phosphorylation for forming large quantities of
ATP. This figure shows the relationship of the oxidative and phosphorylation steps at the outer and inner
membranes of the mitochondrion. Fes, iron sulfide protein; FMN, flavin mononucleotide; Q, ubiquinone.
Chemiosmotic Mechanism

ATP formation during the breakdown of glucose
We can determine the total number of ATP molecules that can formed by the energy of
one molecule of glucose.
By Substrate level Phosphorylation:
• ATP produced by glycolysis: 2ATP
• ATP produced by Krebs Cycle: 2ATP
• Total: 4ATP
By Oxidative phosphorylation:
Oxidative phosphorylation is also needs NADH and FADH2 that produces ATP.
NADH produced by:
1. Glycolysis: 2NADH
2. Link reaction/Pyruvate oxidation: 2NADH
3. Krebs Cycle: 6NADH
4. Total: 10 NADH

FADH2 produced by
 Krebs Cycle: 2-FADH2
 1NADH is equal to the 3ATP under Oxidative phosphorylation.
 1-FADH2 is equal to the 2ATP under Oxidative phosphorylation or ETC.
 So, If 10 NADH enters ETC (electron transport chain) for Oxidative
phosphorylation and FADH2 enter the ETC.
 10NADH×3ATP= 30 ATP
 2-FADH2×2ATP= 4 ATP
 Total= 34 ATP

Total ATP produced by the breakdown of glucose
 By Substrate level of Phosphorylation: 4 ATP
 By the Oxidative phosphorylation: 34 ATP
 Total: 38 ATP
So, the 38 ATP produced by the breakdown of glucose.
 456,000 calories of energy can be stored in the form of ATP.
 Whereas, 686,000 calories are released during the complete oxidation of each molecule of
glucose.
 This represent an overall maximum efficiency of energy transfer 66% energy and 34 %
remaining become heat that cannot used in cell functioning.

Effect of ATP and ADP cell concentration in controlling the rate of
glycolysis
 Continuous release of energy from glucose when the cell do not need energy is a
wasteful process.
 So, the effect of ATP and ADP cell concentration is used in controlling the rate of
glycolysis.
 First way:
 In the first way, ATP inhibits the enzyme phosphofructokinase.
 This enzyme promote the formation of fructose 1,6- diphosphate.
 It can slow the net effect of ATP or stop the glycolysis, in return carbohydrates
metabolism stop.

 Excess ADP produced which then control the glycolysis process is set in
motion.
2nd way:
Excess citrate ions inhibits phosphofructokinase, Thus preventing the process
from getting ahead of citric acid ability to the use of pyruvic acid.
 Conversely, ADP cause the opposite change in this enzyme, it reduces the
inhibition of phosphofructokinase and increase the activity of ADP.

 3rd way:
 ATP,ADP,AMP system controls carbohydrates metabolism, energy released from fats,
protein and various chemicals.
 If all the ADP is converted in to ATP, additional ATP cannot produced.
 As a result entire sequence involved in use of food stuff, glucose and fats and
formation of ATP stop.
 But when the ATP is used to energized the fiction of cell, AMP and ADP are formed
which instantly convert to ATP.

Definition
“Anaerobic glycolysis is a metabolic pathway that converts
glucose to pyruvate without the need for oxygen.”
Anaerobic Release of Energy—
Anaerobic Glycolysis

Steps:
1)Glucose Phosphorylation :
Glucose is phosphorylated to glucose 6-phosphate by hexokinase.
2)Fructose 1,6-bisphosphate cleavage:
Glucose 6-phosphate is converted to fructose 1,6-bisphosphate by
phosphoglucose isomerase and phosphofructokinase.
3)Glyceraldehyde 3-phosphate dehydrogenase:
Fructose 1,6-bisphosphate is cleaved into two three-carbon sugars,
dihydroxyacetone phosphate and glyceraldehyde 3-phosphate.
Dihydroxyacetone phosphate is rapidly converted to glyceraldehyde 3-phosphate
by triose phosphate isomerase.

4)Phosphoglycerate kinase:
Glyceraldehyde 3-phosphate is oxidized to 1,3-bisphosphoglycerate by
glyceraldehyde 3-phosphate dehydrogenase. 1,3-Bisphosphoglycerate then
transfers a phosphate group to ADP to form ATP in a reaction catalyzed by
phosphoglycerate kinase.
5) Phospho glyceromutase:
Phospho glyceromutase shifts the phosphate group from the third carbon to the
second carbon of 3-phosphoglycerate.
6)Enolase:
Enolase dehydrates 2-phosphoglycerate to form phosphoenolpyruvate.
7)Pyruvate kinase:
Pyruvate kinase transfers a phosphate group from phosphoenolpyruvate to ADP
to form ATP in the final step of glycolysis

Products
1) 2 pyruvate molecules
2) 2 ATP molecules
3) 2 NADH molecules
4) 2 H+ ions

Net ATP yield
2 ATP molecules per molecule of glucose

Importance
Anaerobic glycolysis is an important pathway for
energy production during strenuous exercise and in
hypoxic conditions. It is also a major source of lactate,
which is a substrate for gluconeogenesis and a signaling
molecule.

Importance
 Carbohydrate utilise energy and degraded to pyruvic acid by glycolysis and then
oxidize.
 It is not only a process that is used to provide energy.
 Pentose phosphate pathway is another process for breakdown and oxidation of glucose.
 30% of the breakdown of glucose occur in liver.
 It provide energy of all enzyme of citric acid cycle.
 Alternative pathway for energy metabolism when certain enzyme abnormalities occur
in cell.

Explanation
 Pentose phosphate pathway can release one molecule of carbon dioxide and four
atoms of hydrogen with resultant formulation of 5 carbon sugar D-ribulose after
several stages of conversion.
 D-ribulose can change into several other 5,4,7,3 carbon sugar.
 Various combination of these sugar can resynthesized for every 6 molecule of glucose
that initially enter into the reaction.
 Pentose phosphate is a cyclic process in which one molecule of glucose is metabolised
for each revolution of the cycle.

 H can enter the oxidative phosphorylation pathway to form ATP.
 Or for the synthesis of fat or other substance such as NADPH because hydrogen
cannot combine with NAD as in glycolytic pathway.
 But combine with nicotinamide adenine dinucleotide phosphate(NADH) in the form
of NADPH can be used for synthesis of fats from carbohydrates.
 Glycolytic pathway for using glucose becomes slow because of cellular inactivity.
 NADPH is become abandoned to help convert acetyl- CoA also derived from
glucose into long fatty acid chain.

Ways of energy use
1. Formation of ATP
2. In the form of fats

Glucose conversion
 Extra glucose that continuously enter the cell is either store as glycogen or
converted into fat.
 Glucose is preferentially stored as glycogen until the cell can Store.
 Glycogen storing cells (primarily liver and muscle cells)approach saturation
with glycogen.
 Additional glucose convert into fat.

 Formation of the glucose from non-carbohydrate molecules (amino acid and glycerol of fats)
 Primary source for energy in tissues(Brain and RBC ).
 Prevent blood glucose reduction during fasting
 Liver play a key role in maintaining glucose by converting glycogen to glucose that mainly come from
lactate and amino acid.
 25% liver’s glucose synthesized by this process and same process is used for brain’s glucose during faster.
Gluconeogenesis

 When fasting is prolonged kidney prepare glucose from amino acid.
 60% of amino acid in protein is used to make Carbohydrate and other 40% of amino
acid conversion is impossible.
 Complicated amino acid converted into different sugar like 3,4,5,7 carbon atoms and
then phosphoglucose.
 All were done by interconversions.

REGULATION OF GLUCONEOGENESIS
The regulation of gluconeogenesis, the process of making glucose from non-carbohydrate
sources, is primarily controlled by:
Hormones
 Glucagon and cortisol stimulate gluconeogenesis, while insulin inhibits it.
Substrate availability
 High levels of glycerol, lactate, and amino acids provide substrates for gluconeogenesis.

Enzyme regulation
 Key enzymes like PEP carboxykinase and fructose-1,6-bisphosphatase are regulated by
hormones and allosteric factors.
Energy status
 Gluconeogenesis is activated during periods of low blood glucose or increased energy
demand.
Reciprocal regulation
 Gluconeogenesis and glycolysis are reciprocally regulated to maintain
glucose homeostasis.

BLOOD GLUCOSE
Blood glucose, or blood sugar, regulation involves:
Hormones
 Insulin lowers blood glucose, while glucagon raises it.
Glycogen storage
 The liver stores glucose as glycogen when levels are high and releases it when
needed.

Glucose uptake
 Cells take up glucose with the help of insulin receptors.
Dietary intake
Carbohydrate consumption affects blood glucose levels
Gluconeogenesis
 The liver can produce glucose from non-carbohydrate
sources when needed.

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