Biochemistry presentation
Student name: shiraz Khan
Teacher name : sir Imran
Topic name :Glycolyis
PharmD 1st proff
Section ; B
Date 27/3/023
Aerobic glycolyis
● Glycolyis that occurs in presence of oxygen.
● Through the process of glycolysis, one molecule of glucose breaks down to
form two molecules of pyruvate. Depending on the microcellular environment
(specifically, oxygen availability, energy demand, and the presence or
absence of mitochondria), pyruvate has several separate fates
● In mitochondria-containing cells, pyruvate can enter the citric acid cycle within
the mitochondrial matrix and undergo oxidative phosphorylation. It is named
due to its dependence on oxygen as the final electron acceptor, oxidative
phosphorylation cannot take place in the absence of oxygen.
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Aerobic glycolyis
● In aerobic glycolyis Pyruvate passes through oxidative Phosphorylation.
● Through aerobic respiration how many ATP are produced (mcq) ?
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Anaerobic glycolyis
● Glycolyis that occurs in the absence of oxygen.
● Moreover, as the enzymes of both the citric acid cycle and electron transport chain are within the mitochondria,
cells lacking mitochondria (e.g., erythrocytes) cannot rely on oxidative phosphorylation for energy production.
● In erythrocytes and oxygen-deprived tissue, pyruvate remains within the cytoplasm and converts to lactate, a
process referred to as anaerobic glycolysis. This final reaction allows for the regeneration of NAD+, a cofactor
that must be available in high enough intracellular concentrations for the earlier reactions of glycolysis to
remain favorable. Compared to oxidative phosphorylation, however, anaerobic glycolysis is significantly less
efficient, providing a net production of only___ ATP per glucose molecule (versus ___ ATP per glucose
molecule produced during oxidative phosphorylation).
● Under anaerobic conditions, pyruvate has a different fate. Instead of entering mitochondria, the cytosolic
enzyme lactate dehydrogenase converts pyruvate to lactate. Although lactate itself is not utilized by the cell as
a direct energy source, this reaction also allows for the regeneration of NAD+ from NADH. NAD+ is an oxidizing
cofactor necessary to maintain the flow of glucose through glycolysis . 3
Anaerobic glycolyis
● It is a rapid process, approximately ___ times faster than oxidative
phosphorylation.
● Anaerobic glycolysis will tend to slow down as tissue NADH and protons
accumulate to inhibit GAPDH and [Link] (Glyceraldehyde
3-phosphate dehydrogenase
● During anaerobic glycolysis, the reduced cofactor, NADH+ H+ (which eqals
NADH2), formed by the enzyme GAPDH is reconverted to NAD+ during the
formation of lactate.
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Significance of glycolyis
● Glycolysis is the principal route for glucose metabolism for the production of ATP
molecules
● An important biochemical significance is the ability of glycolysis to provide ATP in
the absence of oxygen and allows tissues to survive anoxic episodes.
● It generates precursors for biosynthetic pathway,
● e.g. – Pyruvate may be transaminated to amino acid alanine. In the liver, pyruvate
provides substrate,acetyl-CoA for fatty acid biosynthesis.
● Glycerol-3-phosphate, which is required for the synthesis of triacylglycerol is
derived from glycolytic pathway.
● In erythrocytes, glycolysis supplies 2,3-BPG which is required for the transport of
oxygen by Hb.
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Regulation of glycolysis
1. The glycolytic pathway has a dual role
1. it degrades glucose to generate ATP
2. It provides building blocks for the synthetic reaction such formation of fatty acids
3. In metabolic pathways enzymes catalyzing irreversible reactions are potential sites of
control
4. In glycolysis the reaction catalyzed by :
● Hexokinase
● Phosphofructokinase-I ( pFK) and Pyruvatekinase are virtually irreversible and function as
regulatory enzymes
● The activity of such enzymes can be regulated by
● Allosteric effectors
● Covalent modification
● By increasing or decreasing the amount of these enzymes at the level of transcription.
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Hexokinase and glucokinase
● Hexokinase is an allosteric enzyme, that is inhibited by its product
glucose-6-phosphate.
● Liver glucokinase is an inducible enzyme that increases its synthesis in
response to and decreases in response to glucagon.
Phosphofructokinase-l
● Phosphofructokinase-l is activated by:
● – Fructose-6-phosphate (substrate)
● – AMP (which signals low energy state)
● – Fructose 2,6-bisphosphate.
● Phosphofructokinase-I is inhibited by citrate,c-AMP and ATP (which signals
high energy state slowing down the glycolysis
● Phosphofructokinase-I is an inducible enzyme that increases its synthesis in
response to insulin and decreases in response to glucagon.
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Pyruvate kinase
● Pyruvate kinase is an inducible enzyme that increases in concentration with
high insulin levels and decreases with glucagon.
● It is activated by fructose-1, 6-bisphosphate and inactivated by ATP
8.
Role of fructose 2,6-bisphosphate
in glycolysis
● Fructose 2,6-bisphosphate (F2,6-BP) is considered to be the most important regulatory
factor(activator) for controlling PFK and, ultimately,glycolysis in the liver .F2,6-BP is
synthesized from fructose 6-phosphate by the enzyme phosphofructokinase called
PFK-2 (PFK-1 is the glycolytic glycolytic enzyme).
● F2,6-BP is hydrolysed by fructose 2,6-bisphosphatase. The function ofsynthesis and
degradation of F2,6-BP is broughtout by a single enzyme (same polypeptide withtwo
active sites) which is referred to the enzyme synthesis and degradeF2,6-Bp
● The activity of PFK-2 and fructose 2,6bisphosphatase is controlled by covalent
modification which, in turn, is regulated by cyclic AMP (cAMP is the second messenger
for certain hormones). Cyclic AMP brings about dephosphorylation of the bifunctional
enzyme,resulting in inactivation of active site responsible for the synthesis of F2,6-BP
but activation of the active site responsible for the hydrolysis ofF2,6-BP.
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Role of fructose 2,6-bisphosphate
in glycolysis
● Pyruvate kinase also regulates glycolysis. This enzyme is inhibited by ATP
and activated byF1,6-BP. Pyruvate kinase is active (a) in dephosphorylated
state and inactive (b) in phosphorylated state. Inactivation of pyruvatekinase
by phosphorylation is brought about bycAMP-dependent protein kinase. The
hormone—glucagon inhibits hepatic glycolysis by this mechanism.
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Pasteur effect
● The inhibition of glycolysis by oxygen (aerobic condition) is known as Pasteur
effect.
● It was discovered by Louis Pasteur, more than a century ago, while studying
fermentation by yeast.
● He observed that when anaerobic yeast cultures were exposed to air, the
utiliziation of glucose decreased by nearly seven fold.
● In the aerobic condition, the levels of glycolytic intermediates from fructose
1,6-bisphosphate onwards decrease while the earlier intermediates
accumulate. This clearly indicates that Pasteur effect is due to the inhibition of
the enzyme phosphofructokinase.
● The inhibitory effect of citrate and ATP (produced in the presence of oxygen)
on phosphofructokinaseexplains the Pasteur effect.
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Crabtree effect
● The phenomenon of inhibition of oxygen consumption by the addition of
glucose to tissues having high aerobic glycolysis is known as Crabtree effect.
● Basically, this is opposite to that of Pasteur effect. Crabtree effect is due to
increased competition of glycolysis for inorganic phosphate (Pi) and NAD+
which limits their availability for phosphorylation and oxidation.
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Glycolysis and dental caries
● Dental caries refers to the destruction or decalcification of hard teeth due to
organic acids released by bacterial infections. The anaerobic bacteria (e.g.
Streptococcus mutans,Lactobacillus sps) that colonize the oral cavily
contribute to the development of dental caries.
● These bacteria grow optimally on refined and fermentable sugars (e.g.
sucrose of chocolates, candies) by utilizing anaerobic glycolysis. Lactic acid
and other acids (produced by bacteria) erod tooth enamel and dentin, and
dissolve hydroxyapatite matrix of teeth that results in cavity formation. Low
levels of fluoride, from tooth pastes or when applied topically can inhibit the
enzyme enolase and reduce glycolysis and thus tooth decay. Further, fluoride
integrates into tooth surface to form fluoroapatite which offers resistance to
demineralization
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Glycolyis and dental caries
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pyruvate kinase Difficiency
● Pyruvate kinase deficiency is a condition in which red blood cells break down
faster than they should. This can lead to anemia (not enough red blood ).
● Red blood cells carry oxygen to all parts of the body. Pyruvate kinase helps
make the energy they need to do this. Without enough pyruvate kinase, the
red blood cells don't work as they should and break down too quickly.
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Lactic acidosis
● Lactic acid is a three carbon hydroxy acid. Elevation of lactic acid in the
circulation (normal plasma 4–15 mg/dl) may occur due to its increased
production or decreased utilization.
● Pyruvate is in equilibrium with lactate with a ratio of about 25 lactate to 1
pyruvate molecules. Thus, lactate is the normal endpoint of the anaerobic
breakdown of glucose in the tissues. The lactate exits the cells and is
transported to the liver, where it is oxidized back to pyruvate and ultimately
converted to glucose via the Cori cycle. However, all tissues can use lactate
as an energy source, as it can be converted quickly back to pyruvate and
enter into the Krebs cycle. In the setting of decreased tissue oxygenation,
pyruvate is not readily metabolized and its intracellular levels rise, causing
lactate levels to rise proportionally.
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Hexokinase Difficiency
● Genetic difect in the hexokinase of erythrocyte reduces the amount of
erythrocyte that transport oxygen so reduces the amount of oxygen that is
available for the tissue
● The red blood cell of these patients contain low conc of 2,3-BPG and low
conc of 2,3BPG result in less oxygen available to the tissue and result in
anemia
● 2,3BPG allow hemoglobin to release oxygen to the tissue.
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Mcqs about topic
● How many times anaerobic is faster than aerobic ● In erythrocytes, glycolysis supplies ____ which is
a) 200 required for the transport of oxygen by Hb.
b) 100 a) 3,2-BPG
c) 50 b) 2,3-BPG
d) 10 c) 1,2-BPG
● The step in which ATP production occurs in
d) 2,1BPG
glycolyis is
● In thee conversion of pyruvic acid to lactic acid
a) Preparative phase
b) Oxidative phase which enzyme
c) Reduction phase a) Lactate hydrogenase
d) Energy releasing phase b) Lactate dehydrogenase
c) Lactate oxidase
d) Lactate maltase
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● 1) b
● 2) b
● 3) b
● 4) b
Reference
Satyanarayan biochemistry
Panjak Naik biochemistry
Thank you
Alhamdulillah