Cellular
respiration is a catabolic process which involves the intracellular oxidation
of glucose or organic moleculesthrough
series of enzymatic reaction producing energy in the form of ATP with the
release of CO2 and H2O as byproducts.
This is the summarized video on Electron transport chain
3 stages of cellular respiration:
1. Glycolysis (Glyco=Glucose; lysis= splitting) is the
oxidation of glucose (C 6) to 2 pyruvate (3 C) with the formation of ATP and
NADH.
2.The
Krebs cycle, Citric acid cycle or TCA cycle is an eight step cyclic reactions
in which acetyl CoA is oxidized producing CO2, reduced coenzymes (NADH + H+ and
FADH2), and ATP.
3. Electron Transport Chain:
ETC is
the step by step transfer of high energy electrons through a series of electron
carriers located in multienzyme complexes, finally reducing molecular O2
to form water with the formation of ATP by chemiosmosis.
EXACT SITE OF REACTION
Organelle: Mitochondrion
Site of Electron transport chain: Mitochondrial Inner membrane
Proton (H+) pumped into the intermembrane space creating proton gradient
ATP synthesis occurs towards the matrix region (see the above figure)
Background info: At the beginning of electron transport
chain we have NADH and FADH2 synthesized during Kerb’s cycle and glycolysis.
Approximately only 4 ATP are synthesized directly (2 from glycolysis and 2 from
Krebs cycle) from a glucose molecule. The rest ~32-34 ATP are synthesized
during Electron transport chain (ETC) by chemiosmosis.
Now let as move into the detail
1. Electron flow and Energy release:
NADH and FADH2 donates high energy electrons
that pass through different protein complexes and electron carriers in the ETC.
As the electrons moves from high energy to low
energy level, some amount of energy is released. The final electron acceptor is
O2 which splits and takes up H+ to form water (H2O)
2. Proton movement and gradient formation
The energy released during electron flow is used
to pump proton (H+ ions) from matrix side to the intermembrane space of
mitochondrion. (see figure). This creates a proton gradient
or (Electrochemical gradient or proton motive force) across the inner
mitochondrial membrane (that is higher concentration of H+ ions in the
intermembrane space compared to the matrix).
3. Proton motive force (PMF) driven ATP
synthesis
The H+ ions should move to matrix to maintain
equilibrium (to balance H+ ion concentration). As phopholipid bilayer of inner
mitochondrial membrane is impermeable, the only way out is through the protein
complex called ATP synthase which spans the inner mitochondrial membrane and
has a proton channel.
The flow of H+ ions through ATP synthase
provides energy for the addition of phosphate to ADP thus forming ATP. (just
like turbine in hydroelectric power plant where water forces turbine movement,
here flow of H+ ions drives ATP synthesis)
The proton gradient (Proton motive force) driven
ATP synthesis is called Chemiosmosis.
Hope things are clear. Watch the video for
better understanding. Thank you and enjoy learning Biology
Fats
are macronutrients with highest energy storing potential. They are insoluble in
water.
Ester
bond formation in fats?
Watch this simple 2 minute video
Fats
are
made up of two types of smaller molecules: glycerol and fatty acids
Glycerol
is a 3-C alcohol with a hydroxyl group attached to each carbon
A fatty
acid consists of a carboxyl group attached to a long hydrocarbon skeleton
In a
fat, 3 fatty acids are joined to 1 glycerol by ester linkage, forming triacylglycerol,
or triglyceride
Here the OH of the carboxyl group (-COOH) group of each fatty acid bonds with 1st, 2nd and 3rd carbon OH of the glycerol by ester linkage relaesing 3 molecules of water (H2O)
The
Krebs cycle, Citric acid cycle or TCA cycle is an eight step cyclic reactions
in which acetyl CoA is oxidized producing CO2, reduced coenzymes (NADH + H+ and
FADH2), and ATP.
Site of Reaction:
Mitochondrial matrix in Eukaryotes
Cytoplasm in Prokaryotes
All
enzymes are present in mitochondrial matrix except succinate dehydrogenase
which is bound to inner mitochondrial membrane
Pyruvate
formed in Glycolysis enters mitochondrion and is converted to acetyl CoA which
enters Krebs cycle.
Step 1: Condensation reaction
Acetyl
CoA (C2) is added to oxaloacetate (C4) to form citrate (C6).
Step1
Enzyme: Citrate synthase
Coenzyme
A (CoA-SH) is removed in the process.
Step 2:Isomerization
Citrate
(C6) is isomerized forming isocitrate (C6).
Step2
Enzyme: Aconitase
2
step process: First step involves dehydration of citrate to cis-aconitase
(unstable product)
Second
step involving rehydration of cis-aconitase into isocitrate.
Step 3: Dehydrogenation (1st
NADH synthesis) and decarboxylation(reduction in C atom: C6 to C5)
Isocitrate
(C6) is converted into alphaketoglutarate (C5).
Step3
Enzyme: Isocitrate dehydrogenase
2
step process: First step isocitrate is dehydrogenated to oxalosuccinate (C6)
(intermediate product) NAD+ is reduced, forming NADH + H+
Second
step: Decarboxylation of oxalosuccinate(C6) to α-ketoglutarate (C5).
Carbondioxide is removed.
Coenzyme
A is released, Substrate level phosphorylation of guanosine diphosphate (GDP)
to guanosine triphosphate (GTP). GTP is then hydrolyzed to form ATP
Step 6: Dehydrogenation (FADH2
synthesis)
Succinate(C4)
is converted to fumarate (C4).
Step
6 Enzyme: succinate dehydrogenase in inner mitochondrial membrane
During
this step, FAD is reduced forming FADH2.
Step 7: Hydration
Fumarate(C4)
is converted to malate(C4) with the addition of water.
Step
7 Enzyme: Fumarase (Fumaric acid hydratase)
Step 8: Dehydrogenation
(3rd NADH synthesis)
Final
step: Malate (C4) is converted to oxaloacetate(C4)
Step
8 Enzyme: Malate dehydrogenase
In
the process, NAD+ is reduced to form NADH + H+.
In
metabolic pathways, enzymes catalyzing essentially irreversible reactions are
potential sites of control. In glycolysis, the reactions catalyzed by
hexokinase, phosphofructokinase, and pyruvate kinase are virtually
irreversible; hence, these are the regulatory enzymes in Glycolysis.
This is our 5 minute video Regulatory Enzymes and rate limiting step of Glycolysis
Regulatory Enzyme 1 : Hexokinase
Step 1: Phosphorylation of glucose to glucose-6 phosphate (Hexokinase)
This reaction requires energy and so it is
coupled to the hydrolysis of ATP to ADP and Pi.
• Enzyme: hexokinase. It has a low Km for glucose; hexokinase phosphorylates
glucose that enters the cell
• Irreversible step. So the phosphorylated glucose gets trapped inside thecell.
Glucose transporters transport only free glucose
Hexokinase Activators:AMP/ADP (indicating low
energy or ATP therefore activates hexokinase
Inhibitors: Glucose-6-phosphateInhibitors
If G6P accumulates in the cell, there is
feedback inhibition of hexokinase till the G6P is consumed
Regulatory Enzyme 2 and Rate limiting
step : Phosphofructokinase (PFK)
Step 3: Phosphorylation of fructose-6- bisphosphate.(PFK)
Phosphorylation of the hydroxyl group on
C1forming fructose-1,6- bisphosphate.
Enzyme: phosphofructokinase. This allosteric enzyme regulates the pace of
glycolysis (rate limiting step).
The rate limiting step is the slowest (irreversible) step
in a pathway, which determines how fast the whole pathway can be carried
out.
ATP is used
Second irreversible reaction of the glycolytic pathway.
Definition: In Feed-forward activation, a metabolite
produced early in a pathway activates an enzyme that catalyze a reaction further
down the pathway
Feed Forward activation in Glycolysis
Pyruvate kinase (Step 10 enzyme) is activated by Fructose-1,6-bisphosphate
(3 rd step metabolite)
Fructose-1,6- bisphosphate is formed by the phosphorylation of
fructose-6- bisphosphate by the enzyme Phosphofructokinase (PFK). This
is the committed step or rate limiting step of Glycolysis. Excess Fructose-1,6- bisphosphate in the rate limiting step activates
the formation of final product of the reaction; pyruvate by activating the
enzyme in the final step; pyruvate kinase.
Glycolysis (Glyco=Glucose; lysis= splitting) is the
oxidation of glucose (C 6) to 2 pyruvate (3 C) with the formation of ATP and
NADH.
It is also called as the Embden-Meyerhof
Pathway
Glycolysis is a universal pathway; present in all organisms:
from yeast to mammals.
It is a universal anaerobic process where oxygen is not
required
First phase of cellular reparation in aerobic organisms
It occurs in the cytosol of cell cytoplasm in both
eukaryotes and prokaryotes
In the presence of O2, pyruvate is further
oxidized to CO2.
In the absence of O2, pyruvate can be fermented to lactate or ethanol.
Net Reaction:
Glucose + 2NAD+ + 2 Pi + 2 ADP = 2 pyruvate +
2 ATP + 2NADH + 2 H2O
Here is the video that explains 10 Steps of Glycolysis
2 stages of Glycolysis
First
phase: Preparatory Phase or investment phase Phosphorylation of
Glucose and its conversion to Glyceraldehyde 3-phosphate. 2 ATP used in this
pahse
Second
phase: Payoff phase
Oxidative conversion of Glyceraldehyde 3-phosphate to
pyruvic acid
(4 ATP and 2 NADH produced)
10 Steps of Glycolysis
Reaction 1: Phosphorylation of glucose to glucose-6 phosphate
This reaction
requires energy and so it is coupled to the hydrolysis of ATP to ADP and Pi.
Enzyme: hexokinase (regulatory step). It has a low Km for glucose; hexokinase phosphorylates
glucose that enters the cell
Irreversible step. So the phosphorylated glucose gets trapped inside thecell.
Glucose transporters transport only free glucose
Reaction 2: Isomerization of glucose-6-phosphate to fructose 6-phosphate.
The aldose sugar is converted into the keto isoform.
Enzyme: phosphoglucoisomerase.
This is a reversible reaction. The fructose-6-phosphate is quickly consumed
and the forward reaction is favored.
Reaction 3: is another kinase reaction. Phosphorylation of the hydroxyl
group on C1 forming fructose-1,6- bisphosphate.
Enzyme: phosphofructokinase. This allosteric enzyme regulates the pace of
glycolysis (rate limiting step).
ATP is used
Second irreversible reaction of the glycolytic pathway.
Reaction 4: fructose-1,6-bisphosphate splits into 2 3-carbon molecules,
one aldehyde and one ketone: dihyroxyacetone phosphate (DHAP) and glyceraldehyde
3-phosphate (GAP).
The enzyme is aldolase.
Reaction 5: DHAP and GAP are isomers and can readily inter-convert by the
enzyme triose-phosphate isomerase.
GAP is a substrate for the next step in glycolysis so all of the DHAP is converted
to GAP. So, 2 molecules of GAP are formed from each molecule of glucose
Up to this step 2 ATP is used Second phase: Payoff phase
2 GAP molecules generated from each glucose, therefore each of the remaining reactions
occur twice for each glucose molecule being oxidized.
Reaction 6: GAP is dehydrogenated by the enzyme glyceraldehyde 3-phosphate
dehydrogenase (GAPDH). In the process, NAD+ is reduced to NADH + H+ from NAD. Oxidation
is coupled to the phosphorylation of the C1
carbon.
1,3-bisphosphoglycerate is formed
Reaction 7: This high energy bond of BPG at C-1 is hydrolyzed to a
carboxylic acid and the energy released is used to generate ATP from ADP.
Enzyme:phosphoglycerate kinase.
Product: 3-phosphoglycerate.
Reaction 8: The phosphate group shifts from C3 to C2 to form 2-phosphoglycerate.
Enzyme:phosphoglycerate mutase.
Reaction 9: Dehydration reaction catalyzed by enolase (a lyase). A water
molecule is removed to form phosphoenolpyruvate which has a double bond between
C2 and C3.
Reaction 10: Enolphosphate is a high energy bond. It is hydrolyzed to
form the enolic form of pyruvate with the synthesis of ATP. Irreversible step
Enzyme: pyruvate kinase (regulatory enzyme)
Enol pyruvate quickly changes to a more
stable keto pyruvate.
11.Five Kingdom Classification- Robert H Whittaker
12.Nucleus- Robert Brown
13.Lysosome – Christian de Duve
14.Golgi Complex – Camillo Golgi
15.Mitochondria – Albert von Kolliker (The mitochondria is a double-membraned
cell organelle, known as the powerhouse of the cell which is present in all
eukaryotic cells.It was first discovered by Albert von Kolliker in the year
1857. It was named as bioblast by Richard Altman in the year 1886. The term
mitochondria was coined by Carl Benda in the year 1898.)
16.Gene on Chromosome- Walter S Sutton & Bovery. The term gene
coined by Johannsen
17.Chromosomes-Hofmeister
18.Cell Division (Mitosis) -Walther Flemming & Edward Strasburger
19.Meiosis - Oscar Hertwig (Meiosis was discovered
and described for the first time in sea urchin eggs in 1876 by the German
biologist Oscar Hertwig.)
20.DNA Structure -Watson and Crick
21.Artificial Gene- Har Gobind Khorana
22.Process of Photosynthesis-
Jan Ingenhousz
23.Clavin Cycle- Melvin Calvin
24.Cell Respiration- Adolf Krebs
25.Antigen, Blood Group – Land Steiner
26.Autonomic Nervous System - James Langley
27.Blood Circulation-William
Harvey
28.Blood Transfusion-James
Blundell
29.Pencillin – Alexander Fleming (1928)
30.Insulin – Banting and Best
31.Chloroform – Harrison and Simpson
32.DDT – Paul Muller
33.Stethoscope - Rene Laennec
34.Heart Transplantation – Christian Barnard
35.Vaccination, Smallpox Vaccine – Edward Jenner
36.Louis Pasteur -Treatment of Rabies, Cure of Hydrophobia, Pasteurization
37.Developed one of the first successful polio vaccines
(Injectable) - Jonas Edward Salk
38.Oral Polio Vaccine– Albert Sabin
39.X-Ray – Wilhelm Roentgen
40.ElectroCardioGram (ECG) – Williem Einthoven
41.Electroencephalography (EEG)– Hans Berger
42.PCR (Polymerase Chain Reaction) – Kary B Mullis
43.Colour Blindness –John Dalton
44.Discovered that the Malaria parasite is transmitted by mosquitoes
- Ronald Ross
45.Charles
Louis Alphonse Laveran discovered parasitic protozoans as
causative agents of infectious diseases such as Malaria and Trypanosomiasis.diseases
46.Super
Bug – Anand Mohan Chakrabarty (Developed genetically engineered bacteria
(Pseudomonas, the oil eating bacteria) using plasmid transfer .)
47.Microscope
- Antonie Van Leeuwenhoek
48.Compound
Microscope was invented by
49.Zaccharias
Janssen and Hans Janssen
50.Electron
Microscopewas invented by - Knoll and
Ruska
51.DNA
Fingerprinting- Sir Alec Jeffreys
52.RNA
interference (RNAi) -Andrew Fire & Craig C. Mello
53.ATP
Discovery -Karl Lohmann
54.Enzyme
(Zymase) - Edward Buchne
55.The
first artificial heartJarvik-7 -
Designed by Willem Johan Kolff and Robert Jarvik.
56.Genetic
Code -Marshall Nirenberg
57.SixKingdom Classification- Carl Woese
58.Lamarck
- Theory of Inheritance of Acquired Characters (Lamarckism)
59.Fertilization
in Flowering Plants - Strasburger
60.Discoveries
in relation to Tuberculosis Robert Koch
61.Diphtheria
Antitoxin - Emil von Behring
62.Vitamins
– Hopkins
63.Antiseptic
Surgery - Joseph Lister
64.Magnetic
Resonance Imaging (MRI)-
65.Paul
C. Lauterbur & Sir Peter Mansfield Lister
66.IVF
- Robert Edwards
67.Chemotheraphy
- Paul Ehrlich
68.CT
Scan - Godfrey Hounsfield
69.Gene
Therapy – Anderson
70.Germ
Theory of Disease - Louis Pasteur (Robert Koch isolated specific bacteria that
cause TB and Cholera. He discovered the role of antibodies in immune response)
71.Classical
Conditioning - Ivan Pavlov
72.Principles
of Law of Inheritance- Gregor Mendel Oparin and Haldane
73.Theory of Chemical Evolution of Life -Oparin and Haldane
74.Discovery of Streptomycin - Selman Waksman -
75.Mutation Theory - Hugo de Vries
76.Temin and David Baltimore - Reverse Transcription
77.Artistole - First System of Classification of Living Things
78.Charles Darwin - Theory of Evolution by Natural Selection
79.Barabara Maclintok - Jumping Gene in Maize
80.First Cloned Mammal(Dolly) - Ian Wilmut
81.August Weismann -Germplasm theory
82.Green Fluorescent Protein (GFP) -
Osamu Shimomura
83.First
Hormone (Secretin) -Ernest Starling and William Bayliss
84.HeLa First Immortal Cell
line -George Otto Gey
85.(Acetyl Co A) Neurotransmitter - Otto Loewi
86.DNA Polymerase - Arthur Kornberg (1956)
87.First Recombinant (rDNA) molecule - Paul Berg
88.Law of
Minimum -Nitrogen
as essential nutrient in Plant - Liebig
89.The alpha helix and beta sheet in Protein
Secondary Structure - Linus Pauling
90.Discovery
of Restriction Enzymes and their application in Molecular Genetics -Arber,
Nathans, and Smith
91.Theory of Chemical Evolution of Life
92.Concept
of 'Ecosystem' - A G Tansley
93.Chromatography
- Mikhail Tswett
94.Gene
Linkage - William Bateson
95.DNA as
Genetic Material - Avery–MacLeod–McCarty
96.Central
Dogma of Molecular Biology- Francis Crick
97.Gene
Reguation Mechanismin Prokaryotes (Lac
Operon) - Jacob and Monod
98.Boveri–Sutton
Chromosome Theory(Chromosome
Theory of Inheritance)
99.Dideoxy
DNA Sequencing Method- Maxam–Gilbert and Sanger
100.Addison's
disease - Thomas Addison
101.Ribozyme
(Catalytic RNAs)-Sidney
Altman and Thomas Cech
102.Gene
discovery using Express Sequence Tags (ESTs)- Craig Venter
103.Molecular
Mechanisms of Circadian Rhythm -Dr. Michael Rosbash, Dr. Jeffrey Hall,Dr.
Michael Young
