This presentation is about bioenergetics. It talks about energy changes and equilibrium during different biological reactions, how exergonic and endergonic reactions are combined as sequential reactions in body, how the body system is following the law of thermodynamics etc. Role of enzymes in thermodynamics is also explained
This presentation is about bioenergetics. It talks about energy changes and equilibrium during different biological reactions, how exergonic and endergonic reactions are combined as sequential reactions in body, how the body system is following the law of thermodynamics etc. Role of enzymes in thermodynamics is also explained
Energy and the biological systems are joined together and no biological world is almost impossible without ATP. This study material intends to explore the beauty of ATP to drive different biological processes.
Basic information about the four law of Thermodynamics with chemistry point of view.
8 slide = Chemical Reactions
16 slide = Reversible and Non-Reversible Reactions
KEY CONCEPTS
8.1 An organism’s metabolism transforms matter and
energy, subject to the laws of thermodynamics
8.2 The free-energy change of a reaction tells us whether or not the reaction occurs
spontaneously
8.3 ATP powers cellular work by coupling exergonic reactions to endergonic reactions
8.4 Enzymes speed up metabolic reactions by lowering energy barriers
8.5 Regulation of enzyme activity helps control metabolism
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
More Related Content
Similar to BIOENERGETICS of Metabolism of Various Metabolic Processes
Energy and the biological systems are joined together and no biological world is almost impossible without ATP. This study material intends to explore the beauty of ATP to drive different biological processes.
Basic information about the four law of Thermodynamics with chemistry point of view.
8 slide = Chemical Reactions
16 slide = Reversible and Non-Reversible Reactions
KEY CONCEPTS
8.1 An organism’s metabolism transforms matter and
energy, subject to the laws of thermodynamics
8.2 The free-energy change of a reaction tells us whether or not the reaction occurs
spontaneously
8.3 ATP powers cellular work by coupling exergonic reactions to endergonic reactions
8.4 Enzymes speed up metabolic reactions by lowering energy barriers
8.5 Regulation of enzyme activity helps control metabolism
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
TEST BANK For Williams' Essentials of Nutrition and Diet Therapy, 13th Editio...kevinkariuki227
TEST BANK For Williams' Essentials of Nutrition and Diet Therapy, 13th Edition Schlenker & Gilbert, Verified Chapters 1 - 25, Complete Newest Version.pdf
TEST BANK For Williams' Essentials of Nutrition and Diet Therapy, 13th Edition Schlenker & Gilbert, Verified Chapters 1 - 25, Complete Newest Version.pdf
TEST BANK For Timby's Introductory Medical-Surgical Nursing, 13th American Ed...kevinkariuki227
TEST BANK For Timby's Introductory Medical-Surgical Nursing, 13th American Edition by Donnelly-Moreno, Verified Chapters 1 - 72, Complete Newest Version.pdf
TEST BANK For Timby's Introductory Medical-Surgical Nursing, 13th American Edition by Donnelly-Moreno, Verified Chapters 1 - 72, Complete Newest Version.pdf
EATING DISORDERS (Psychiatry-7)by dr Shivam sharma.pptxShivam Sharma
For any queries ,contact shvmshrm@outlook.com
---
## Introduction to Eating Disorders
Welcome to this comprehensive presentation on Eating Disorders, a critical and often misunderstood area of mental health. This presentation is designed to provide in-depth knowledge and insights into the various aspects of eating disorders, making it valuable for both postgraduate medical aspirants preparing for the INI-CET and the general public seeking to understand these complex conditions.
### Objectives:
1. **Understanding Eating Disorders**: Gain a clear understanding of what eating disorders are, their types, and their distinguishing characteristics.
2. **Etiology and Risk Factors**: Explore the underlying causes and risk factors that contribute to the development of eating disorders.
3. **Clinical Features and Diagnosis**: Learn about the clinical features, diagnostic criteria, and the importance of early detection.
4. **Management and Treatment**: Review the current approaches to managing and treating eating disorders, including medical, psychological, and nutritional interventions.
5. **Prevention and Awareness**: Discuss strategies for prevention, early intervention, and increasing awareness about eating disorders.
This presentation aims to bridge the gap between academic knowledge and practical understanding, providing you with the tools to recognize, diagnose, and effectively manage eating disorders. Whether you are preparing for a medical exam or seeking to educate yourself or others about these serious conditions, this presentation will equip you with essential information and practical insights.
Let's begin our journey into understanding eating disorders and the significant impact they have on individuals and society.
---
For any queries ,contact shvmshrm@outlook.com
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Why invest into infodemic management in health emergenciesTina Purnat
A lecture discussing the challenge of health misinformation and information ecosystem in public health, how this impacts demand promotion in health, and how this then relates to responding to misinformation and infodemics in health emergencies. Appended with lots of tools, guidance and resources for people who want to do more reading.
Mastering Wealth: A Path to Financial FreedomFatimaMary4
### Understanding Wealth: A Comprehensive Guide
Wealth is a multifaceted concept that extends beyond mere financial assets. It encompasses a range of elements including money, investments, property, and other valuable resources. However, true wealth also includes non-material aspects such as health, relationships, and personal fulfillment. This guide delves into the various dimensions of wealth, exploring how it can be created, sustained, and enjoyed.
#### Defining Wealth
Traditionally, wealth is defined as the abundance of valuable resources or material possessions. It includes financial assets like cash, savings, stocks, bonds, and real estate. However, a broader understanding of wealth considers factors such as personal well-being, emotional health, social connections, and intellectual growth. This holistic view recognizes that true wealth is not solely about accumulating money but also about enhancing one's quality of life.
#### The Importance of Financial Wealth
Financial wealth remains a critical component of overall wealth. It provides security, freedom, and the ability to pursue opportunities. Key elements of financial wealth include:
1. **Savings**: Money set aside for future use. It is crucial for emergencies, large purchases, and financial goals.
2. **Investments**: Assets purchased with the expectation that they will generate income or appreciate over time. Common investments include stocks, bonds, mutual funds, real estate, and businesses.
3. **Income**: Regular earnings from work, investments, or other sources. Consistent income is essential for maintaining and growing wealth.
4. **Debt Management**: Effectively managing debt ensures that it does not erode financial wealth. This includes paying off high-interest debt and using credit wisely.
#### Creating Wealth
Creating wealth involves generating and accumulating financial and non-financial resources. The process can be broken down into several key strategies:
1. Education and Skill Development: Investing in education and skills enhances earning potential. Higher education, professional certifications, and continuous learning can lead to better job opportunities and higher salaries.
2. Entrepreneurship: Starting and running a successful business can be a significant source of wealth. Entrepreneurship requires innovation, risk-taking, and effective management.
3. Investing: Making smart investments is essential for wealth creation. This involves understanding different types of investments, assessing risks, and making informed decisions. Diversifying investments can reduce risk and increase potential returns.
4. Saving and Budgeting: Effective saving and budgeting help accumulate wealth over time. Setting financial goals, creating a budget, and sticking to it are foundational steps in wealth creation.
5. Real Estate: Investing in property can provide rental income and capital appreciation. Real estate is a tangible asset that can hedge against inflation
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TEST BANK For Advanced Practice Nursing in the Care of Older Adults, 2nd Edit...kevinkariuki227
TEST BANK For Advanced Practice Nursing in the Care of Older Adults, 2nd Edition by Laurie Kennedy-Malone, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK For Advanced Practice Nursing in the Care of Older Adults, 2nd Edition by Laurie Kennedy-Malone, Verified Chapters 1 - 19, Complete Newest Version.pdf
2. • Living organisms must work to stay alive, to
grow and to reproduce
• All living organisms have the ability to
produce energy and to channel it into
biological work
• Living organisms carry out energy
transductions, conversions of one form of
energy to another form
3. • Modern organisms use the chemical
energy in fuels (carbonhydrates, lipids) to
bring about the synthesis of complex
macromolecules from simple precursors
• They also convert the chemical energy
into concentration gradients and electrical
gradients, into motion and heat, and, in a
few organisms into light (fireflies, some
deep-sea fishes)
4. • Biological energy transductions obey the
same physical laws that govern all other
natural processes
• Bioenergetics is the quantitative study of the
energy transductions that occur in living cells
and of the nature and function of the chemical
process underlying these transductions
5. Goals of this lecture
• Review the laws of thermodynamics
• Understand the quantitative relationships
among free energy, enthalpi and entropy
• Describe the special role of ATP in
biological energy exchanges
7. Laws of thermodynamics
• 1. For any physical or chemical change,
the total amount of energy in the universe
remains constant; energy may changed
from or it may be transported from one
region to another, but it can not be
created or destroyed
8. • 2. The universe always tends toward
increasing disorder: in all natural
processes the entropy of the universe
increases
9. • The reacting system may be an organism, a
cell or two reacting compounds. The reacting
system and its surroundings together
constitute the universe.
• In the laboratory some chemical or physical
processes can be carried out in closed
systems and no material or energy is
exchanged with the surroundings
• However living organisms are open systems.
They exchange both material and energy
with their surroundings
10. • Living systems are never at equilibrium with
their surroundings
• Gibbs free energy (G): G expresses the
amount of energy capable of doing work
during a reaction at constant temperature
and pressure.
11. • When a reaction proceeds with the release
of free energy (that is, when the system
changes so as to posses less free energy)
ΔG has a negative value and the reaction
is said to be exergonic
• In endergonic reactions, the system gains
free energy and ΔG is positive
• The unit of ΔG is joules/mole or
calories/mole
12. • Enthalpy (H): H is the heat content of the
reacting system. H reflects the number
and kinds of chemical bounds in the
reactants and products.
• When a chemical reaction releases heat, it
is said to be exothermic, the heat content
of the products is less than that of the
reactants and ΔH has a negative value
• Reacting systems that take up heat from
their surroundings are endothermic and
have positive values of ΔH
13. • The unit of ΔH is joules/mole or
calories/mole
• Entropy (S): S is a quantitative expression
for the randomness or a disorder in a
system
• The unit of ΔS is joules/mole. Kelvin
14. • Under the constant temperature and pressure
changes in free energy, enthalpy and entropy in
biological systems are related to each other by
the equation
• ΔG= ΔH - TΔS
• ΔG= Change in Gibbs free energy of the
reacting system (Gproducts– Greactives)
• ΔH= Change in enthalpy of the reacting
system(Hproducts – Hreactives)
• T= Absolute temperature
• ΔS= Change in entropy of the reacting
system(Sproducts – Sreactives)
15. • Living organisms preserve their internal
order by taking free energy from their
surroundings in the form of nutrients or
sunlight and returning to their
surroundings an equal amount of energy
as heat and entropy
16. Example:The oxidation of glucose
• Aerobic organisms extract free energy from
glucose obtained from their surrouindings by
oxidizing the glucose with oxygen (also
obtained from surroundings). The end products
of this oxidation reaction are CO2 and H2O and
they are returned to the surroundings. At the
end of this process, the surroundings undergo
an increase in entropy, whereas the organism
itself remains in a steady state and no change
occurs in its internal order
17.
18. • Whenever a chemical reaction results in
an increase in the number of molecules
the entropy of the surroundings increases
• Whenever a solid substance is converted
into liquid or gaseous forms the entropy of
the surroundings increases. Because this
transformations allow the molecule more
freedom for movement
19. Cells require sources of free energy
• Living organisms acquire free energy from
nutrient molecules. Cells transform this
free energy into ATP and other energy-rich
compounds
• They are capable of providing energy for
biological work at constant temparature.
20. • The composition of a reacting system tends to
continue changing until equilibrium is reached.
At the equilibrium the rates of the forward and
revers reactions are equal and no further
change occurs in the system.
21. • The Keq is defined by the molar
concentrations of products and reactants
at equilibrium
• aA+bB cC+ dD
• [C]c [D]d
• Keq =
• [A]a [B]b
22. • When a reacting system is not at equilibrium,
the tendency to move toward the equilibrium
represents a driving force. The magnitude of this
driving force is expressed as free energy
change (ΔG).
•
• Under standard conditions (250C), when
reactants and products are initially at the 1 M
concentrations the force driving the system
toward equilibrium is defined as the
standard free energy change (ΔG0)
23. • By this definiation, standart state for reactions
involves [H+] = 1M or pH=0.
• However most biochemical reactions occur in
well-buffered aqueous solutions near pH=7
• For convenience of calculations, biochemists
define a different standard state in which the
concentration of [H+] is 10-7 M , and for
reactions that involve Mg2+ (available in most
reactions involving ATP), its concentration in
solution is commonly taken to be constant at
1mM
•
24. • Physical constants based on this biochemical
standard state are called standard
transformed constants and written as ΔG'0
and K'eq to distinguish them from the
untransformed constants which are used by
chemists.
25. • ΔG'0 is the difference between the free energy
content of the products and the free energy
contents of the reactants under standard
conditions
• ΔG'0 = ΔG'0
products– ΔG'0
reactives)
• When ΔG'0 is negative, the products contain
less free energy than the reactants and the
reaction will proceed spontaneously under
standard conditions
• When ΔG'0 is positive, the products contain
more free energy than the reactants and the
reaction will tend to go in the revers direction
under standard conditions
26. • Each chemical reaction has a characteristic
standard free energy change which may be
positive, negative or zero depending on the
equilibrium constant of the reaction
• ΔG'0 tell us in which direction and how far a
given reaction must go to reach equilibrium
when the initial concentration of each
component is 1M, the pH is 7, the temparature
is 250C.
• Thus ΔG'0 is a constant; a characteristic for a
given reaction
27. Actual free energy change
• Actual free energy change (ΔG) is a function
of reactant and product concentrations and of
the temparature prevailing during the reaction
which will not necessarily match the standard
conditions as defined before
28. • ΔG of any reaction proceeding spontaneously
toward its equilibrium is always negative,
become less negative as the reaction proceeds,
and is zero at he point of equilibrium, indicating
that no more work can be done by the reaction
• ΔG and ΔG'0 for a reaction like that
• A+B C+D
• is written as
• [C] [D]
• ΔG=ΔG'0 + RTln
• [A] [B]
29. • An example:
• A+B C+D
• Reaction is taking place at the standard
temparature and pressure
• But the concentrations of A,B,C and D are not
equal and none of them at the 1M concentration
• In order to determine actual ΔG under these
non-standard concentrations as the reaction
proceeds from left to right, we enter the actual
concentrations of A,B,C and D in this equation.
30. • Rest of the terms in the equation (R,T, ΔG'0 )
are standard values
• When the reaction is at equilibrium there is no
force driving the reaction in either direction and
ΔG is zero, thus equation reduces to
• [C] [D]
• 0= ΔG'0 + RTln
• [A] [B]
• ΔG'0 = -RT lnK'eq ΔG'0
31. • The criteria for spontaneity of a reaction is
the value of ΔG not ΔG'0
• Standard free energy changes are additive.
• In the case of two sequential chemical reactions,
• A B ΔG'0
1
• B C ΔG'0
2
32. • Since the two reactions are sequential, we
can write the overall reaction as
• A C ΔG'0
total
• The ΔG'0 values of sequential reactions
are additive.
• ΔG'0
total = ΔG'0
1 + ΔG'0
2
33. • A B ΔG'0
1
• B C ΔG'0
2
• Sum: A C ΔG'0
1 + ΔG'0
2
• This principle of bioenergetics explains how
a thermodynamically unfavorable
(endergonic) reaction can be driven in the
forward direction by coupling it to a highly
exergonic reaction through a common
intermediate
34. • The main rule in biochemical reactions in
living organisms:
• All endergonic reactions are coupled to
an exergonic reaction. There is an
energy cycle in cells that links anabolic
and catabolic reactions.
35. An example: The first step of glycolysis
• Glucose + Pi Glucose 6-phosphate+H2O
• ΔG'0 =13,8 kj/mol
• ΔG'0 >0 reaction is not spontaneous
36. • Another very exergonic cellular reaction:
• Hydrolysis of ATP
• ATP + H2O ADP + Pi
• ΔG'0 = -30,5 kj/mol
• These two reactions share the common
intermediates H2O and Pi and may be
expressed as sequential reactions:
37. • Glucose + Pi Glucose 6-phosphate+H2O
• ATP + H2O ADP + Pi
• Sum: Glucose+ATP Glucose 6-phosphate+ADP
• The overall standard free energy changes:
• ΔG'0 =13,8 kj/mol + (-30,5 kj/mol)= -16,7
kj/mol
• Overall reaction is exergonic
38. • Energy stored in ATP is used to drive to
synthesis of glycose 6-phosphate,
eventhough its formation from glucose and Pi
is endergonic.
• This strategy works only if compounds such
as ATP are continuously available.
39. Phosphoryl group transfer and ATP
• Living cells obtain free energy in a chemical
form by the catabolism of nutrient molecules
• They use that energy to make ATP from ADP
and Pi .
• ATP donates some of its chemical energy to
• 1. Endergonic processes such as the
synthesis of metabolic intermediates and
macromolecules from smaller precursors
40. • 2. The transport of substances across
membranes against concentration gradients
• 3. Mechanical motion (muscle contraction)
• This donation of energy from ATP can occur in
the two form
• A) ATP ADP+ Pi or
• B) ATP AMP+ 2 Pi
41. The free energy change for ATP
hydrolysis is large and negative
• The hydrolytic cleavage of the terminal
phosphoanhydride bond in ATP separates
one of the three negatively charged
phosphates and thus relieves some of the
electrostatic repulsion in ATP
• Released Pi is stabilized by the formation
of several resonance forms not possible in
ATP
42. • ADP2- is the other product of hydrolysis
and it immediately ionizes, releasing H+
into a medium of very low [H+] ( ̴ 10-7 M)
• Because the concentrations of the
products ot ATP hydrolysis are far below
the concentrations at equilibrium, mass
action favors the hydrolysis in the cell
43.
44. • Although the hydrolysis of ATP is highly
exergonic (ΔG'0 = -30,5 kj/mol), the ATP is
stable at pH 7, because the activation
energy for ATP hydrolysis is relatively high.
Rapid hydrolysis of ATP occurs only when
catalyzed by an enzyme
45. • The free energy change for ATP hydrolysis is
-30,5 kj/mol under standard conditions but
the actual free energy change (ΔG) of ATP
hydrolysis in living cells is very different.
• The cellular concentrations of ATP, ADP and
Pi are not same and are much lower than the
1 M standard conditions.
• In addition, Mg2+ in the cytosol binds to ATP
and ADP and for most enzymatic reactions
that involve ATP as phosphorly group donor,
the true substrate is MgATP-2. The relevant
ΔG'0 is therefore that for MgATP-2 hydrolysis.
46.
47. Compounds have large free
energy change
• Phosphorylated compounds
• Thioesters (Acetyl-CoA)
49. Phosphoenolpyruvate
• Phosphoenolpyruvate contains a phosphate ester
bond that undergoes to yield to enol form of pyruvate
• The enol form of pyruvate can immediately
tautomerize to the more stable keto form of pyruvate.
Because phosphoenolpyruvate has only one form
(enol) and the product, pyruvate, has two possible
forms, the product is more stabilized relative to the
reactant.
• This is the greatest contributing factor to the high
standard free energy change of hydrolysis of
phosphoenolpyruvate (ΔG'0 = -61,9 kj/mol)
50.
51. 1,3-bisphosphoglycerate
• 1,3-bisphosphoglycerate contains an
anhydride bond between the carboxyl group at
C-1 and phosphoric acid.
• Hydrolysis of this acyl phosphate is
accompanied by a large, negative, standard
free energy change (ΔG'0 = -49,3 kj/mol)
• This large, negative ΔG'0 can, again, be
explained in terms of the structure of reactants
and products
•
52. • When the water is added to anhyhride
bond of 1,3-bisphosphoglycerate, one of
the direct products, 3-phosphoglyceric
acid, can immediately lose a proton to give
the carboxylate ion, 3-phosphoglycerate,
which has two equally probable resonance
forms
• Removal of a direct product, 3-phospho-
glyceric acid, and formation of resonance-
stabilized ion favor the forward reaction.
53.
54. Phosphocreatine
• In the phosphocreatine, the P-N bond can
be hydrolyzed to generate free creatine
and Pi. The release of Pi and the
resonance stabilization of creatine favor
the forward reaction. The standard free
energy change of phosphocreatine is large
and negative (ΔG'0 = -49,3 kj/mol).
55.
56. Thioesters
• In thioesters a sulfur atom is replaced the
usual oxygen in the ester bond
• Thioesters have large, negative standard free
energy change of hydrolysis.
• Acetyl coenzyme A is one of many thioesters
important in metabolism. The acyl group in
these compounds is activated for trans-
acylation, condensation or oxidation-reduction
reactions.
57. • Hydrolysis of the ester bond generates a
carboxylic acid which can ionize and
assume several resonance forms.
• ΔG'0 = -31,4 kj/mol for acetyl-CoA hydrolysis
58.
59. Summary for hydrolysis reactions
• For hydrolysis reactions with large, negative
standard free energy changes, the products
are more stable than the reactants for one
or more of the following reasons:
• 1. The bond strain in reactants due to
electrostatic repulsion is relieved by charge
separation, as for ATP
• 2. The products are stabilized by ionization,
as for ATP, acyl phosphates, thioesters
60. • 3. The products are stabilized by isomerization
(tautomerization) as for phosphoenolpyruvate
• 4. The products are stabilized by resonance as
for creatine released from phosphocreatine,
carboxylate ion released from acyl phosphates
and thioesters and phosphate released from
anhydride or ester linkages
61. • The phosphate compounds found in living
organisms can be arbitrarily divided into two
groups based on their standard free energy
changes of hydrolysis.
• ‘High-energy’ compounds have a ΔG'0 of
hydrolysis more negative than -25 kj/mol; ‘low-
energy’ compounds have a less negative ΔG'0.
• Based on this criterion, ATP, with a ΔG'0 of
hydrolysis of -30 kj/mol is a high-energy
compound; glucose 6-phosphate is a low-
energy compound (ΔG'0 = -13,8 kj/mol)
62.
63. • The term ‘high-energy phosphate bond’
was used by biochemists to describe P-O
bond broken in hydrolysis reactions for a
long time. But it is incorrect and misleading
as it wrongly suggests that the bond itself
contains the energy.
• In fact, the breaking of all chemical bonds
requires an input of energy. The free
energy released by hydrolysis of phosphate
compounds does not come from the
specific bond that is broken;
64. • it results from the products of the reaction
having a lower free energy content than
the reactants
65. • As is evident from the additivity of free
energy changes of sequential reactions,
any phosphorylated compound can be
synthesized by coupling the synthesis to
the breakdown of another phosphorylated
compound with a more negative standard
free energy change of hydrolysis.
66. • Example:
• ΔG'0
• PEP + H2O Pyruvate + Pi -61,9
• ADP+ Pi ATP+ H2O +30,5
• +
• PEP + ADP Pyruvate + ATP -31,4
• Clevage of Pi from PEP releases more energy
than is needed to drive to condensation of Pi
with ADP, the direct donation of a phosphoryl
group from PEP to ADP is thermodynamically
feasible.
67. • Notice that while the overall reaction
above is represented as the algebraic sum
of first two reactions, the overall reaction
(third) does not involve Pi ; PEP donates a
phosphoryl group directly to ADP.
• We can describe phosphorylated
compounds as having a high or low
phosphoryl group transfer potential, on
the basis of their standard free energy
changes of hydrolysis
68. • Much of catabolism is directed toward the
synthesis of high-energy phosphate
compounds, but their formation is not an end
in itself; they are the means of activeting a
wide variety of compounds for further chemical
transformation.
• The transfer of a phosphoryl group to a
compound effectively puts free energy into that
compound, so that it has more free energy to
give up during subsequent metabolic
transformations.
69. • Because of its intermediate position on the
scale of group transfer potential, ATP can
carry energy from high-energy phosphate
compounds produced by catabolism to
compounds such as glucose, converting
them into more reactive species.
• ATP serves as the universal energy currency
in all living cells
70. • One more chemical feature of ATP is crucial
to its role in metabolism: although in
aqueous solution ATP is thermo-
dynamically unstable and is therefore a
good phosphoryl group donor, it is
kinetically stable.
• Because of high activation energies required
for uncatalyzed reaction ATP does not
spontaneously donate phosphoryl groups to
water or to the other potential acceptors in
the cell.
71. • ATP hydrolysis occurs only when specific
enzymes which lower the energy of
activation are present
• The cell is therefore able to regulate the
disposition of the energy carried by ATP
by regulating the various enzymes that act
on ATP
• Each of the three phosphates of ATP is
susceptible to nucleophilic attack and each
position of attack yields a different type of
product
72.
73. • Attack at the Ɣ phosphate displaces ADP and
transfers Pi,
• Attack at the ϐ phosphate displaces AMP and
transfers PPi,
• Attack at the α phosphate displaces PPi and
transfers adenylate
• Notice that hydrolysis of phospho anhydride bond
between α and ϐ phosphates releases much more
energy than hydrolysis of phospho anhydride bond
between ϐ and Ɣ phosphates. Because PPi formed
as a by-product of the adenylation is hydrolyzed the
two Pi releasing and thereby providing a further
energy push for the adenylation reaction
74. Examples
• Fatty acid activation reactions during the
fatty acid synthesis and /or oxidation
• Amino acid activation reactions during the
protein synthesis
• DNA and RNA synthesis
75. • Direct hydrolysis of ATP (ATP ADP+Pi )
is the source of energy in the conformational
changes that produce muscle contraction and
transport an ion or a molecule across a
membrane against concentration gradient (An
example: Na+- K+ exchange by Na+ K+
ATPaz)
76. Transphosphorylations between
nucleotides
• Although we have focused on ATP as the
cell’s energy currency and donor of phosphoryl
groups, all other nucleoside triphosphates
(GTP, UTP, CTP) and all the deoxynucleoside
triphosphates (dATP, dGTP, dTTP and dCTP)
are energetically equivalent to ATP. The free
energy changes associated with hydrolysis of
their phosphoanhydride linkages are very
nearly identical with those for ATP.
77. • In preparation for their various biological roles,
these other nucleotides are generated as the
nucleoside triphosphate (NTP) forms by
phosphoryl group transfer to the corresponding
nucleoside diphosphates (NDPs) and
monophosphates (NMPs)
• ATP is the primary high-energy phosphate
compound produced by catabolism in the
processes of glycolysis, oxidative
phosphorylation. Several enzymes carry
phosphoryl groups from ATP to the other
nucleotides
78. • Nucleoside diphosphate kinases, found in all
cells, catalyzes the reaction
• Mg2+
• ATP+NDP(or dNDP) ADP+NTP(or dNDP)
• Although this reaction is fully reversible the
relatively high ATP/ADP ratio in cells normally
drives the reaction to the right, with the net
formation of NTPs and dNTPs
•
79. • Phosphoryl group transfers from ATP result in
an accumulation of ADP. For example, when
muscle is concracting vigorously ADP
accumulates and interferes with ATP-
dependent contraction.
• During periods of intense demand for ATP, the
cell lowers the ADP concentration, and at the
same time acquires ATP, by the action of
adenylate kinase:
• Mg2+
• 2ADP ATP + AMP
80. • This reaction is fully reversible, so after the
intense demand for ATP ends, the enzyme can
recycle AMP by converting it to ADP which can
then be phosphorylated to ATP in mitochondria
• A similar enzyme guanylate kinase, converts
GMP to GDP at the expense of ATP. By-
pathways such as these, energy conserved in
the catabolic production of ATP is used to
supply the cell with all required NTPs and
dNTPs
81. • Phosphocreatine (PCr) serves as a ready
source of phosphoryl groups for the quick
synthesis of ATP from ADP. The
phosphocreatine concentration in skeletal
muscle is considerably higher than those in
the other tissues. The enzyme creatine
kinase catalyzes the reversible reaction.
• Mg2+
• ADP+ PCr ATP+Cr
• ΔG'0 = -12,5
kj/mol
82. • When a sudden demand for energy depletes
ATP, the PCr reservoir is used to replenish
ATP at a rate faster than ATP can be
synthesized by catabolic pathways
• When the demand for energy slackens ATP
produced by catabolism is used to replenish
the PCr reservoir by reversal of the creatine
kinase reaction
83. SUMMARY
• ATP is the chemical link between catabolism
and anabolism. The exergonic conversion of
ATP coupled to many endergonic processes
in living organisms
• Cells also contain some high-energy
compounds which have a high
phosphorylation potential, like ATP. They are
good donors of phosphoryl groups.