This ppt is about Heme synthesis and include all the steps that are included in heme synthesis. This is a Powerpoint presentation made for students of MBBS 1st year by Devashish Bisht.
This ppt is about Heme synthesis and include all the steps that are included in heme synthesis. This is a Powerpoint presentation made for students of MBBS 1st year by Devashish Bisht.
This is the glycolysis component of Bioc (chem) 361 at UAE University. Some from Campbell 6th ed and the rest from General, Organic, and Biochemistry, 5th edition (2007), by K.J.Denniston, J.J.Topping, and R.L.Caret.
What is glycolysis?
Ten step metabolic pathway to convert glucose into two molecules of pyruvate and two molecules each of NADH and ATP.
All carbohydrates to be catabolized must enter the glycolytic pathway.
Glycolysis is central in generating both energy and metabolic intermediaries.
Also known as Embden-Meyerhof-Parnas (EMP) pathway
Complete Set of Metabolism of Carbohydrate in that second chapter, glycolysis.
This presentation covers complete glycolysis pathway with step wise animated reactions and it includes clinical aspects also. This presentation is good for MBBS students.
What is glycolysis?
Ten step metabolic pathway to convert glucose into two molecules of pyruvate and two molecules each of NADH and ATP.
All carbohydrates to be catabolized must enter the glycolytic pathway.
Glycolysis is central in generating both energy and metabolic intermediaries.
Also known as Embden-Meyerhof-Parnas (EMP) pathway
This presentation has detailed information on glycolysis. each step is explained in detail. there are certain videos which i have taken from youtube. if these videos are not viewable u can refer to shomus biology glycolysis videos. u will get a detailed info there.
lehninger 3rd edition is also very good for the structures
Happy studying :)
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
5. Glycolytic pathway, is the oxidation of
glucose to pyruvate to produce energy
(ATP and NADH + H) and other
metabolic intermediates.
6. The process of glucose oxidation to
pyruvate is called glycolysis.
Glycolysis is a process that takes place
both aerobic and anaerobic conditions.
The fate of pyruvate is determined by
the presence of oxygen in the tissue
and the presence or absence of
mitochondria.
7. Aerobic/Anaerobic Glycolysis
In fact, under aerobic and unaerobic
conditions the reactions are the same
until the production of pyruvate from
glucose.
The end product of glycolysis in cells
with mitochondria and enough oxygen
is is pyruvate (aerobic glycolysis).
Conversion of glucose to lactate is the
anaerobic glycolysis.
8. 6 CH OPO 2−
2
3
5
O
H
4
OH
H
OH
3
H
H
2
H
1
OH
OH
glucose-6-phosphate
Glycolysis takes place in the cytosol of cells.
Glucose enters the Glycolysis pathway by
conversion to glucose-6-phosphate.
9. • Glucose gets phosphorylated rapidly after
entering the cell.
• Phosphorylation of glucose prevents it from
getting out of the cell.
10. 6 CH2OH
5
H
4
OH
O
H
OH
H
2
3
H
OH
glucose
ATP
H
1
OH
6 CH OPO 2−
2
3
ADP
H
Mg2+
5
4
OH
Hexokinase
O
H
OH
3
H
H
1
H
2
OH
OH
glucose-6-phosphate
• ATP is required for this rxn. Glucose gets a
phosphate group from ATP and becomes
glucose-6-phosphate.
11. 6 CH2OH
5
H
4
OH
O
H
OH
H
2
3
H
OH
glucose
6 CH OPO 2−
2
3
5
O
ATP ADP
H
H
1
OH
Mg2+
4
OH
H
OH
3
H
2
H
1
OH
Hexokinase H
OH
glucose-6-phosphate
1. Hexokinase catalyzes:
Glucose + ATP glucose-6-P + ADP
The reaction is between hydroxyl O of C6 of glucose
and the terminal phosphate of ATP.
ATP binds to the enzyme as a complex with Mg++.
13. 6 CH OPO 2−
2
3
5
O
H
4
OH
H
OH
3
H
H
2
OH
H
1
OH
6 CH OPO 2−
2
3
1CH2OH
O
5
H
H
4
OH
HO
2
3 OH
H
Phosphoglucose Isomerase
glucose-6-phosphate
fructose-6-phosphate
2. Phosphoglucose Isomerase catalyzes:
glucose-6-P (aldose) fructose-6-P (ketose)
The mechanism involves acid/base catalysis, with ring
opening, isomerization, and then ring closure. A
similar reaction catalyzed by Triosephosphate
Isomerase will be presented in detail.
14. 6 CH OPO 2−
2
3
5
H
4
OH
O
H
OH
3
H
H
2
OH
H
1
OH
6 CH OPO 2−
2
3
1 CH2OH
O
5
H
H
4
OH
HO
3
H
2
OH
Phosphoglucose Isomerase
glucose-6-phosphate
fructose-6-phosphate
• Isomerization of an aldose sugar (glucose 6
phosphate) to a ketose sugar (fructose 6phosphate)
15. Phosphofructokinase
6 CH OPO 2−
2
3
1CH2OH
O
5
H
H
4
OH
ATP ADP
HO
2
3 OH
H
fructose-6-phosphate
6 CH OPO 2−
2
3
O
5
Mg2+
1CH2OPO32−
H
H
4
OH
HO
2
3 OH
H
fructose-1,6-bisphosphate
3. Phosphofructokinase catalyzes:
fructose-6-P + ATP fructose-1,6-bisP + ADP
This highly spontaneous reaction has a mechanism similar
to that of Hexokinase.
The Phosphofructokinase reaction is the rate-limiting step
of Glycolysis.
The enzyme is highly regulated, as will be discussed later.
16. A phosphate group is
transferred to the first C of
fructose 6 phosphate from
ATP.
Phosphofructokinase
6 CH OPO 2−
2
3
1CH2OH
O
5
H
H
4
OH
ATP ADP
HO
2
3 OH
H
fructose-6-phosphate
6 CH OPO 2−
2
3
O
5
Mg2+
1CH2OPO32−
H
H
4
OH
HO
2
3 OH
H
fructose-1,6-bisphosphate
20. • dihydroxyacetone-P must be isomerirized to
glyceraldehyde-3-P for futher metabolism in
the glycolytic pathway.
• This isomerization results in the production of
2 mol. of glyceraldehyde-3-P from the
cleavage products of fructose 1,6 biphosphate..
26. Phosphoglycerate Kinase
O−
OPO32−ADP ATP O
O
1C
H 2C OH
Mg2+
2−
3 CH2OPO3
1,3-bisphosphoglycerate
C
1
H 2C OH
2−
3 CH2OPO3
3-phosphoglycerate
7. Phosphoglycerate Kinase catalyzes:
1,3-bisphosphoglycerate + ADP
3-phosphoglycerate + ATP
The high energy phophate of 1,3-bisphosphoglycerate is used to
synthesize ATP from ADP. 2 mol. of 1,3-bisphosphoglycerate
are formed from each glucose therefore 2 ATP mol. Are
replaced that were used first during the formation of glucose 6
phosphate and fructose 1,6 biphophosphate.
27. Phosphoglycerate Mutase
O−
O
C
1
O−
O
C
1
H 2C OH
CH2OPO32−
3
H 2C OPO32−
3 CH2OH
3-phosphoglycerate
2-phosphoglycerate
8. Phosphoglycerate Mutase catalyzes:
3-phosphoglycerate 2-phosphoglycerate
Phosphate is shifted from the OH on C3 to the
OH on C2.
28. Phosphoglycerate Mutase
O−
O
C
1
histidine
O−
O
C
1
H 2C OH
CH2OPO32−
3
H 2C OPO32−
3 CH2OH
3-phosphoglycerate
2-phosphoglycerate
An active site histidine side-chain
participates in Pi transfer, by
donating & accepting phosphate.
The process involves a
2,3-bisphosphate intermediate.
O−
O
C
1
H 2C OPO32−
2−
3 CH2OPO3
2,3-bisphosphoglycerate
29. Enolase
−
O
O
C
1
H 2 C OPO32−
3 CH2OH
H+ −
O
−
O
C
C
OH−
O−
O
1
OPO32−
CH2OH
C
2C
OPO32−
3 CH2
2-phosphoglycerate enolate intermediate phosphoenolpyruvate
9. Enolase catalyzes:
2-phosphoglycerate phosphoenolpyruvate + H2O
The dehydration of 2-phosphoglycerate by enolase reaction
is Mg++-dependent.
2 Mg++ ions interact with oxygen atoms of the substrate
carboxyl group at the active site.
33. glyceraldehyde-3-phosphate
NAD+ + Pi
Glyceraldehyde-3-phosphate
Dehydrogenase
NADH + H+
Glycolysis
continued.
Recall that
there are 2
GAP per
glucose.
1,3-bisphosphoglycerate
ADP
Phosphoglycerate Kinase
ATP
3-phosphoglycerate
Phosphoglycerate Mutase
2-phosphoglycerate
Enolase
H2O
phosphoenolpyruvate
ADP
Pyruvate Kinase
ATP
pyruvate
34. Glycolysis
Balance sheet for ~P bonds of ATP:
2
How many ATP ~P bonds expended? ________
How many ~P bonds of ATP produced? (Remember
4
there are two 3C fragments from glucose.) ________
Net production of ~P bonds of ATP per glucose:
2
________
35. Balance sheet for ~P bonds of ATP:
2 ATP expended
4 ATP produced (2 from each of two 3C fragments
from glucose)
Net production of 2 ~P bonds of ATP per glucose.
Glycolysis - total pathway, omitting H+:
glucose + 2 NAD+ + 2 ADP + 2 Pi
2 pyruvate + 2 NADH + 2 ATP
In aerobic organisms:
pyruvate produced in Glycolysis is oxidized to CO2
via Krebs Cycle
NADH produced in Glycolysis & Krebs Cycle is
reoxidized via the respiratory chain, with production
of much additional ATP.
36. Lactate Dehydrogenase
O−
O
C
C
NADH + H+ NAD+
O
O−
O
C
HC
OH
CH3
CH3
pyruvate
lactate
E.g., Lactate Dehydrogenase catalyzes reduction of
the keto in pyruvate to a hydroxyl, yielding lactate, as
NADH is oxidized to NAD+.
Lactate, in addition to being an end-product of
fermentation, serves as a mobile form of nutrient energy,
& possibly as a signal molecule in mammalian organisms.
Cell membranes contain carrier proteins that facilitate
transport of lactate.
37. Lactate Dehydrogenase
O−
O
C
C
NADH + H+ NAD+
O
O−
O
C
HC
OH
CH3
CH3
pyruvate
lactate
Skeletal muscles ferment glucose to lactate during
exercise, when the exertion is brief and intense.
Lactate released to the blood may be taken up by other
tissues, or by skeletal muscle after exercise, and converted
via Lactate Dehydrogenase back to pyruvate, which may
be oxidized in Krebs Cycle or (in liver) converted to back
to glucose via gluconeogenesis
38. Lactate Dehydrogenase
O−
O
C
C
NADH + H+ NAD+
O
O−
O
C
HC
OH
CH3
CH3
pyruvate
lactate
Lactate serves as a fuel source for cardiac muscle as
well as brain neurons.
Astrocytes, which surround and protect neurons in the
brain, ferment glucose to lactate and release it.
Lactate taken up by adjacent neurons is converted to
pyruvate that is oxidized via Krebs Cycle.
39. Pyruvate
Decarboxylase
Alcohol
Dehydrogenase
CO2
NADH + H+ NAD+
O−
O
C
C
O
CH3
pyruvate
H
O
C
CH3
acetaldehyde
H
H
C
OH
CH3
ethanol
Some anaerobic organisms metabolize pyruvate to
ethanol, which is excreted as a waste product.
NADH is converted to NAD+ in the reaction
catalyzed by Alcohol Dehydrogenase.
40. Glycolysis, omitting H+:
glucose + 2 NAD+ + 2 ADP + 2 Pi
2 pyruvate + 2 NADH + 2 ATP
Fermentation, from glucose to lactate:
glucose + 2 ADP + 2 Pi 2 lactate + 2 ATP
Anaerobic catabolism of glucose yields only 2 “high
energy” bonds of ATP.
41. Flux through the Glycolysis pathway is regulated by
control of 3 enzymes that catalyze spontaneous reactions:
Hexokinase, Phosphofructokinase & Pyruvate Kinase.
Local control of metabolism involves regulatory effects
of varied concentrations of pathway substrates or
intermediates, to benefit the cell.
Global control is for the benefit of the whole organism,
& often involves hormone-activated signal cascades.
Liver cells have major roles in metabolism, including
maintaining blood levels various of nutrients such as
glucose. Thus global control especially involves liver.
Some aspects of global control by hormone-activated
signal cascades will be discussed later.
42. 6 CH2OH
5
H
4
OH
O
H
OH
H
2
3
H
OH
glucose
6 CH OPO 2−
2
3
5
O
ATP ADP
H
H
1
OH
Mg2+
4
OH
H
OH
3
H
2
H
1
OH
Hexokinase H
OH
glucose-6-phosphate
Hexokinase is inhibited by product glucose-6-phosphate:
by competition at the active site
by allosteric interaction at a separate enzyme site.
Cells trap glucose by phosphorylating it, preventing exit
on glucose carriers.
Product inhibition of Hexokinase ensures that cells will
not continue to accumulate glucose from the blood, if
43. 6 CH2OH
5
H
Glucokinase
is a variant of
Hexokinase
found in liver.
4
OH
O
H
OH
H
2
3
H
OH
glucose
6 CH OPO 2−
2
3
5
O
ATP ADP
H
H
1
OH
Mg2+
4
OH
H
OH
3
H
1
H
2
OH
Hexokinase H
OH
glucose-6-phosphate
Glucokinase has a high KM for glucose.
It is active only at high [glucose].
One effect of insulin, a hormone produced when blood
glucose is high, is activation in liver of transcription of
the gene that encodes the Glucokinase enzyme.
Glucokinase is not subject to product inhibition by
glucose-6-phosphate. Liver will take up & phosphorylate
glucose even when liver [glucose-6-phosphate] is high.
44. Glucokinase is subject to inhibition by glucokinase
regulatory protein (GKRP).
The ratio of Glucokinase to GKRP in liver changes in
different metabolic states, providing a mechanism for
modulating glucose phosphorylation.
45. Glycogen
Glucose
Hexokinase or Glucokinase
Glucose-6-Pase
Glucose-6-P
Glucose + Pi
Glycolysis
Pathway
Glucokinase,
with high KM
Glucose-1-P
for glucose,
allows liver to
store glucose
Pyruvate
as glycogen in
Glucose metabolism in liver.
the fed state
when
blood [glucose] is high. catalyzes hydrolytic release of P
Glucose-6-phosphatase
i
from glucose-6-P. Thus glucose is released from the liver
to the blood as needed to maintain blood [glucose].
The enzymes Glucokinase & Glucose-6-phosphatase, both
found in liver but not in most other body cells, allow the
liver to control blood [glucose].
46. Pyruvate Kinase
−
O
O
Pyruvate Kinase, the
ADP
C
last step Glycolysis, is
1
C OPO32−
controlled in liver partly
2
by modulation of the
3 CH2
amount of enzyme.
phosphoenolpyruvate
ATP
O−
O
C
1
C
2
O
3 CH3
pyruvate
High [glucose] within liver cells causes a transcription
factor carbohydrate responsive element binding protein
(ChREBP) to be transferred into the nucleus, where it
activates transcription of the gene for Pyruvate Kinase.
This facilitates converting excess glucose to pyruvate,
which is metabolized to acetyl-CoA, the main precursor
for synthesis of fatty acids, for long term energy storage.
47. Phosphofructokinase
6 CH OPO 2−
2
3
1CH2OH
O
5
H
H
4
OH
ATP ADP
HO
2
3 OH
H
fructose-6-phosphate
6 CH OPO 2−
2
3
O
5
Mg2+
1CH2OPO32−
H
H
4
OH
HO
2
3 OH
H
fructose-1,6-bisphosphate
Phosphofructokinase is usually the rate-limiting step of
the Glycolysis pathway.
Phosphofructokinase is allosterically inhibited by ATP.
At low concentration, the substrate ATP binds only at
the active site.
At high concentration, ATP binds also at a low-affinity
regulatory site, promoting the tense conformation.
48. 60
low [ATP]
PFK Activity
50
40
30
high [ATP]
20
10
0
0
0.5
1
1.5
[Fructose-6-phosphate] mM
2
The tense conformation of PFK, at high [ATP], has lower
affinity for the other substrate, fructose-6-P. Sigmoidal
dependence of reaction rate on [fructose-6-P] is seen.
AMP, present at significant levels only when there is
extensive ATP hydrolysis, antagonizes effects of high ATP.
49. Glycogen
Glucose-1-P
Glucose
Hexokinase or Glucokinase
Glucose-6-Pase
Glucose-6-P
Glucose + Pi
Glycolysis
Pathway
Pyruvate
Glucose metabolism in liver.
Inhibition of the Glycolysis enzyme Phosphofructokinase
when [ATP] is high prevents breakdown of glucose in a
pathway whose main role is to make ATP.
It is more useful to the cell to store glucose as glycogen
when ATP is plentiful.
50. Glycolysis:
Specific tissue functions
RBC’s
Rely exclusively for energy
Skeletal muscle
Source of energy during exercise, particularly high
intensity exercise
Adipose tissue
Source of glycerol-P for TG synthesis
Source of acetyl-CoA for FA synthesis
Liver
Source of acetyl-CoA for FA synthesis
Source of glycerol-P for TG synthesis