Download MBBS (Bachelor of Medicine, Bachelor of Surgery) 1st year (First Year) Biochemistry ppt lectures Topic 63 Integrated Metabolism Notes. - biochemistry notes pdf, biochemistry mbbs 1st year notes pdf, biochemistry mbbs notes pdf, biochemistry lecture notes, paramedical biochemistry notes, medical biochemistry pdf, biochemistry lecture notes 2022 ppt, biochemistry pdf.
Induction To Todays Topic
WORLD OF HUMAN BEINGS
HUMAN INTER-RELATIONSHIPS
WORLD OF BIOMOLECULES
And
INTER-RELATIONSHIPS
ANY GUESSES FOR TODAYS TOPIC ?
Integrated Metabolism
OR
Intermediary Metabolism
OR
Interrelationship Between
Various Metabolic Pathways
OR
Interdependence Of Metabolic
Pathways
What Is an Essence of
Normal, Health, Growth and Reproduction
of Human Body?
Normal Metabolism of Biomolecules
Metabolism and Types
Important Factors Of Metabolism
?Metabolites
?Hormones
?Enzymes
?Cofactors
?Coenzymes
?Water
?Oxygen
? Various metabolic reactions, pathways and
processes of important biomolecules of human
body viz:
? Carbohydrates
? Lipids
? Proteins
? Nucleic acids
? Hemoglobin
? Taking place in different cells and cellular
compartments of specific tissues and organs.
Significance To Study
Individual Metabolic Pathways
Of Various Biomolecules
? Metabolism of each chief
biomolecule was studied
individual y and separately.
? For convenience and clear
understandings of metabolic
reactions associated to it.
Features of
Normal Metabolic Pathways
1. Well Planned
2. Compartmentalized
3. Well Organized/ More Systematic
4. Require Specific Conditions
5. Synergistic/Simultaneous
6. Flexible/Adapt/Change for good survival
7. Induced as per condition
8. Regular in its operation
9. Regulated/Control ed/Balanced
10. Good cooperation and coordination
Hormones Regulate Metabolism
? Hormones are key regulators of
Enzymes
? Regulatory Enzymes are stimulated or
inhibited by specific hormones
? Enzymes are regulated by:
?Al osteric Regulation
?Covalent Modifications
Metabolism Is Regulated By
? Availability of Substrates Regulate
Metabolism :
?Ratio of Insulin/Glucagon
?Ratio of ATP and AMP
?NADH/NAD
?Citrate levels
?Fructose 2,6 Bisphosphate levels
? Low and high levels of ATP stimulate and
inhibit regulatory enzymes of Glycolysis and
TCA.
? Increased levels of Acetyl-CoA and Citrate
stimulates enzyme Acetyl CoA Carboxylase
of De Novo biosynthesis of Fatty acid.
? Increased Fructose 1,6 Bisphosphatase is
? Al osteric stimulator of PFK of Glycolysis
? Al osteric inhibitor of Fru1,6Bis Phosphatase
of Gluconeogenesis.
What is an Integrated Metabolism?
? Metabolic pathways are Closely
Interrelated/Integrated
/Interdependent
?Not total y dependent nor total y
independent
OR
?But partial dependence and partial
independence
Stages Of Integrated Metabolism
Evidences Of
Metabolic Interrelationships
Interrelationships
Of
Carbohydrates with Lipid Metabolism
Free Excess of Glucose
In Wel Fed Condition
Is a Source For Lipogenesis
Acetyl-CoA Obtained from
Glucose Metabolism
Is Precursor for
Lipid Metabolism
(Fatty acids and Cholesterol)
? Pyruvate (3C Keto acid) an end product
of Glycolysis is oxidatively
decarboxylated to Acetyl-CoA
? Acetyl-CoA is then utilized via TCA
cycle
? Acetyl-CoA obtained from Glucose
when excess is diverted and used for
biosynthesis of Fatty acids and
Cholesterol.
Glyceraldehyde Of Glycolysis
Integrated as Glycerol
of
TAG and Glycerophospholipid
? Glyceraldehyde-3-phosphate an
intermediate of Glycolysis of Glucose ,
is a source for Glycerol production.
? Glycerol obtained from Glucose is
utilized during Lipogenesis ,for
biosynthesis of Triacylglycerol and
Phospholipid biosynthesis.
? Thus when Carbohydrates
ingested in excess can be
transformed to TAG which is
? Stored as reserve source of
energy in Adiposecytes
Interrelationships
Of
TCA Cycle
TCA Cycle
Is an
Excellent Example
of
Integrated Metabolism
? TCA cycle intermediates are very
significant
? These intermediates are influxed
and effluxed as per the cel ular
need and maintain biochemical
Homeostasis. (Anaplerotic
Reactions)
Efflux of TCA Intermediates
? Citrate ? Denovo Biosynthesis of Fatty
acids.
? OAA is reversibly transaminated to
Aspartate.
? Ketoglutarate reversibly transaminated
to Glutamate.
? Succinyl CoA is effluxed for Heme
biosynthesis and Ketolysis.
Influx of TCA Cycle Intermediates
? Ketoglutarate is added by Glutamate by it's
Glutamate Dehydrogenase activity.
? Succinyl -CoA is obtained from Propionyl-CoA
which is a source from B-oxidation of odd chain
fatty acid
? Catabolism of Valine, Isoleucine & Methionine
(VIM) amino acids forms Succinyl-CoA.
? Fumarate is influxed through
Phenylalanine & Tyrosine
metabolism
? Fumarate also through Urea
cycle by Argininosuccinase
activity.
Points To Remember
? TCA intermediates are involved
for biosynthesis of:
I. Glucose
I . Amino acids
I I. Fatty acids And Cholesterol
IV. Heme
Interrelationship Of
TCA with Urea Cycle
Interrelationships Of
Lipid With Carbohydrate
Metabolism
Fat Burns Under Flame of
Carbohydrates
? Fat burns under the Flame of
Carbohydrates
? For complete oxidation of Fatty
acids
? Their needs presence of
sufficient amount of cel ular
Glucose.
Oxaloacetate Serves Flame for Complete
Oxidation Of Fatty acid
? In a well fed condition
? Major source for OAA is
Glucose
? By Pyruvate Carboxylase
activity
?Oxaloacetate is an
essential initiating
metabolite for TCA cycle
?Oxaloacetate (OAA)
serve as a flame for
oxidation of Acetyl
CoA via TCA cycle.
? Cel ular deprivation of Glucose
lowers OAA leads to incomplete
oxidation of Fatty acids.
? Accumulates Acetyl-CoA in
Mitochondrial matrix.
? Impermeable Acetyl-CoA is then
transformed to permeable ketone
bodies via ketogenesis.
-oxidation of Fatty acid and it's
Interrelationship
? Reduced coenzymes FADH2 &
NADH+H+ generated during it's
pathway are
? Integrated with ETC /oxidative
phosphorylation to generate
ATP.
?Acetyl-CoA formed as an end
product of oxidation of
fatty acids
?Is integrated with TCA cycle
for it's complete oxidation.
? Acetyl-coA can be a source for
Ketone bodies production via
Ketogenesis.
? To smal extent in normal
metabolic conditions and excess
in emergency conditions.
Remember
Fatty acids
cannot be converted
to Glucose In Human
Body
? Acetyl-CoA obtained from Beta-
oxidation of fatty acids cannot be
reversibly converted to Pyruvate
? Since PDH complex is irreversible in
action.
? Thus there is no net conversion of
Fatty acids (Fat) to Glucose
(Carbohydrates).
? However Propionyl-CoA an end
product of oxidation of odd chain
fatty acid
? Serve as a source for Glucose
production after conversion into
Succinyl-CoA (intermediate of TCA
cycle)
? Succinyl-CoA in turn can be a source
for Heme synthesis and Ketolysis.
Interrelationship
Of
Carbohydrates
And
Protein Metabolism
? Intermediates of Glucose
metabolism can be a source of
? Carbon skeleton for biosynthesis of
non Essential amino acids.
vPyruvate to Alanine
vOAA to Aspartate
vKetoglutarate to Glutamate
Amino Acids And Its Interrelationships
Amino acids are interrelated
for
Purine and Pyrimidine
biosynthesis
?Gly , Asp, Gln for Purine Biosynthesis
?Asp and Gln for Pyrimidine Synthesis
Amino acids are Source
For Glucose In Human Body
? Glucogenic amino acids are source
for production of Glucose via
Gluconeogenesis.
? 100 gm of Proteins can produce
approx 60 gm of Glucose in human
body.
?Amino acid Glycine is
connected to Heme
biosynthesis.
? Glycerol released during
lipolysis of TAG is integrated
? With Gluconeogenesis to
produce Glucose.
HMP Shunt and It's lnterrelationships
? Glucose is alternatively oxidized
through HMP shunt to generate:
? NADPH+H+ (reducing equivalents)
? Ribose-5- phosphate
? NADPH+H+ are integrated to:
*Biosynthesis of Fatty acids
*Biosynthesis of Cholesterol
*Drug metabolism
? Ribose-5-phosphate
(pentose sugar) of HMP
shunt is integrated for
?Biosynthesis of Purine &
Pyrimidine Nucleotides.
Interrelationships of
Uronic acid pathway
?Glucuronic acid is involved
in Mucopolysaccharide
biosynthesis.
? Glucuronic acid of Uronic acid
pathway is integrated with Phase
I conjugation reactions of
detoxification process.
?Glucuronic acid is involved in:
?Bilirubin metabolism
?Drug metabolism
Interrelationship Of ETC
? Reduced coenzyme NADH+H+
generated in Glycolysis
? By action of Glyceraldehyde? 3 ?
Phosphate Dehydrogenase
? Enter in ETC for its reoxidation
and ATP generation.
ATP and Its Interrelationships
? ATP produced during oxidative
phosphorylation are connected to:
I. Nerve impulse conduction
I . Muscular activity
I I. Active transport mechanism
IV. Biosynthetic Reactions
V. Activation Reactions
Crossroads Of Metabolism
OR
Metabolites of Cross Roads
v Four Important Metabolites in
human body who function as
crossroads of metabolism :
1. Glucose-6-Phosphate
2. Pyruvate
3. Acetyl-CoA
4. Oxaloacetate (OAA)
5. Succinyl-CoA
Formation And Fates
Of
Pyruvate
Formation And Fates
Of
Acetyl CoA
Formation And Fates Of Oxaloacetate
And
Formation And Fates Of Succinyl-CoA
Metabolites Forming
Non essential Amino acids
In Human Body
Phosphoenolpyruvate
Phenylalanine Tyrosine Tryptophan
Tyrosine
Ribose 5-phosphate
Histidine
Pyruvate
Alanine Valine Leucine
a-Ketoglutarate
Glutamate
Glutamine Proline Arginine
3-Phosphoglycerate
Serine
Glycine
Cysteine
Oxaloacetate
Aspartate
Asparagine Methionine Threonine Lysine
Isoleucine
Metabolic Profile
And
Interrelationship Among Organs
Important Metabolic Organs
And Their
Interrelationships
Metabolic Profile of Organs
121
Liver
? Biochemical Factory of Human body
? Metabolical y very active in all states
(well fed and fasting)
? Most Cooperative and Coordinated
organ/Understands responsibility and
does its work (Dutiful/Pious Organ)
Liver is a Glucostatic Organ
Regulates Blood Glucose
in al conditions
The wel -fed state:
Insulin stimulates glucose consumption and
Stimulated by an
storage in muscle and liver.
increase in blood
glucose level.
Stored as glycogen
or triacyglycerol.
?In a wel fed condition Liver stores
excess free Glucose as Glycogen
(Glycogenesis)
?In emergency condition In Liver
Glycogen is degraded via
Glycogenolysis and biosynthesizes
Glucose via Gluconeogenesis.
?Liver biosynthesizes
endogenous Lipids and
mobilizes out it as VLDL
for extra hepatic use.
?Liver Centre of Ammonia
Detoxification
Muscles
? In a normal metabolic state
muscle uses Glucose and Fatty
acids as main sources of energy.
? In a well fed state muscles has
large stores of Glycogen (3/4th)
? In contracting muscles during severe
exercise in anaerobic condition
Glycolysis ends as Lactate.
? Later Lactate is metabolized by
converting it into Glucose after carried
through blood in Liver via
Gluconeogenesis (Cori cycle).
?In resting Muscle fatty
acids are the major source
of energy
?This use spare Glucose to
be used by Brain and
Erythrocytes.
Metabolic cooperation between
the skeletal muscle and liver.
The Cori Cycle
Metabolic Profile of Muscles
136
Adipose Tissue
? TAG can be abundantly and
unlimitedly stored in adipocytes
? TAG serve as a reserve store of
energy during well fed condition.
? TAG is the major fuel for this
tissue.
Metabolic Profile of Adipose Tissue
? Needs Glucose for biosynthesis of TAG
? Glucose level determines to release
Fatty acids into blood
? Hormone sensitive Lipase is activated
when Insulin/Glucagon ratio is low
Brain
? Glucose is the main fuel of Brain
(120 gm/day)
? Fatty acids cannot be utilized by
brain as they are bound to Albumin
and cannot cross blood brain
barrier.
Metabolic Profile of Brain
60-70 % of bodies utilization of Glucose is
by Brain.
In starvation -> Ketone bodies can
replace Glucose
Brain is a major
Glucose consumer
Fatty acids do not serve as a fuel!
Consumes about 120 g
glucose daily.
Erythrocytes
? Erythrocytes uses obligatorily Glucose as
a source of energy for its activity.
? Erythrocytes cannot use Fatty acids and
Ketone bodies as source of energy.
? It lacks Mitochondria hence the
Glycolysis ends in Lactate.
Metabolic Profile of Kidney
? Filtration of Blood- Plasma Ultra Filtrate
? Reabsorption ,Secretion of Substances
? From Plasma Ultra filtrate -> Water , Glucose important
absorbable metabolites reabsorbed as per the threshold
values.
? Production of Urine -> Secretion of waste products
? Important role in water, electrolyte ,acid base balance.
? During Starvation -> Important site of Gluconeogenesis
(1/2 of blood Glucose)
145
In Human Body
There Prevails
Chemical Unity In Diversity
? Intermediates/End Products of one metabolic
pathway may be connected to another
metabolic pathway of same or another.
? An end product of one metabolic
pathway of Carbohydrate is connected to
another metabolic pathway of
Carbohydrate.
? Intermediate of Carbohydrate metabolic
pathway is interrelated to a metabolic
pathway of Lipid or Nucleic acid.
Integration of Fuel Metabolism
Purine
Uric acids
Glycogen
Ribose-5-P
monophosphate
PRPP
Pyrimidine
G-6-P
monophosphate
Glycine
Serine
G-3-P
Malonyl CoA
Fatty acids
b-Oxidation
PEP
Acetoacetyl CoA
Cholesterol
Acetyl CoA
Other
Pyruvate
amino
Triacylglycerols
Oxaloacetate
acids
Alanine
TCA
Aspartate
Cycle a
Other
-ketoglutarate
Urea
amino
Urea
Other
Glutamate acids
Cycle
amino
Glutamine
acids
Why Metabolic Pathways are
Integrated?
OR
What Is the Significance Of
Integrated Metabolism
To Human Body?
Integrated Metabolism Occurs To
1. To Interconvert biochemical metabolites as
per the cel ular need
2. To meet the bodies fuel demand
3. To regulate levels of intermediary
metabolites and maintain their equilibrium
4. To coordinate with various cel s, tissues
and organs for existence
5. To impart normal biochemical
environment and maintain health
?A well coordinated and
regulated integrated
metabolism of human
body
?Protects from metabolic
catastrophes.
Significance Of
Knowledge Of Integrated Metabolism
To Doctors
? Prerequisite to Become A Good
Doctor Is to:
?Acquire Profound Knowledge of
Integrated Metabolism
?With Good Understanding
Biochemical Concepts And its
Interrelationships
Doctors Responsibility
Health Professionalist
? To Heal and Relieve Pain of Patients
? To Understand Sign Symptoms
? Correlate with Biochemical basis
? Depict Biochemical Alteration
? Confirm diagnosis
? Control, treat biochemical alterations of a
disordered patients
? Study of integrated metabolism with their
interrelationships in a normal healthy conditions
helps a doctor :
? To better understand various deranged
metabolic conditions and related complexities
? Rule out right biochemical underlying cause of
metabolic disorders and pathogenesis
? Try correct an altered metabolism in treatment
Take Home Messages
Interrelationship Of Human
Biochemical System
A good Doctor is one
Who has An
Understanding Knowledge of
Intermediary Metabolism
Questions
? Long Essays.
? Q.1.Describe the common metabolic pathway.
OR
? Why TCA cycle is called as common metabolic
pathway? Explain with reactions.
? Q.2.Explain "Fat burns under the flame of
Carbohydrates".
?Which metabolic pathway
is an excellent example of
integrated metabolism?
Justify it.
? Q.3.How Carbohydrate, Lipid & Protein
metabolic pathways are integrated &
interrelated with each other. Explain
with the help of flow diagram.
? Q.4.Explain the three stages in the
intermediary metabolism of
Carbohydrate, Lipid & Protein.
?Influx & Efflux of TCA
intermediates.
?Integration of TCA with
Urea cycle.
?Formation and Fates of
? Pyruvate
?Acetyl-CoA
?Succinyl-CoA
?Oxaloacetate
?-Ketoglutarate
? Q.5.Describe the role of
fol owing organs during
wel fed condition.
?Liver
?Brain
?Muscles
?Adipose tissues
THANK YOU
Dr Anissa Atif Mirza
Biochemistry Department
AI MS Rishikesh
Important Tips For
4/4/2022
183
Three Gifts For Human Beings
On Which Health And Success Depend Upon
How Best they are Utilized
For Significant/Good Long Term Outcome
?Body- Sense
?Time
?Energy
Factors For Quality Of Health
Normal State Of Biomolecules and Metabolism
? Intentions and Actions= Behavior (Sleep Cycle)
? Nutrition (Food Cycle)
? Environment (Companionship)
Health Factors
Il Health Factors
Positive Behavior- Sensibly
Negative Behavior- Carefree
,thoughtful ,rightful care of body ,Uncontrolled, dysregulated
by Controlled ,Regulated with
activities with disobedience rigid
obedient implementation's of Do's non implementations of Do's and
of Health and Avoid Don'ts of
high implementations of Don'ts
Health
Balanced Diet- Simple and Natural Imbalanced Diet with more
Appropriate Quality and Quantity processed and refined with poor
of all essential nutrients
quality and improper quantity of
nutrients
Proper Sleep- Time 7-8 Hrs
Improper Sleep with low time in
(Early To Bed and Early To Rise)
night and more time in day
Environment- Natural Unpolluted Environment ?
Companionship with ?
Polluted with physical, chemical
Good ,Positive, Helpers
and biological pollutants
Companions with ?
Bad,Negative,Distractors
Biomolecules And Their Processes Responsible For Health
Similar Features Implemented In Practical Human Life wil
impart Success
1. Focused and Specific
2. Implement rules and regulations/orders of
metabolism (Obedient)
3. Interdependence -Communicate and
Cooperate
4. Disciplined and Dutiful-Responsible/Sensible
5. No two works at a time- For maintaining ful
Concentration
6. Complete one priority work and start Next
priority -
7. Not much multitasking/Very few multitasking as per
need
8. Do Not get overloaded at one time
9. Understand situation and work accordingly (Adapt as
per condition)
10. Sparing actions, Distribute (Charity, Share and Care)
11. Work with good pace in regularity
12. Proof Read -No Chance of Mistakes/Less errors
13. Defined and Refined- Limitations
14. Homeostasize to be in limit and do not cross limits
15. Productive/Significant-Non Futile (Economical
,Reutilizes ,No wastage)
Tips To Ensure Good ,Healthy Life
? Live Life
? Thoughtful y,Righteously,Carefuly,Actively,Alertly
? Eat Balanced
? Proportionate Quantity and Appropriate Quality
? Drink and Breathe
? Unpol uted Water and Air
? Cultivate Cheerfulness
? Love,Share,Care,
? Thankfulness,Politeness,Selflessness
? Avoid Synthetic, Chemical Interactions
? Chemical, Inhibitions leads to Disorders
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189
Live a Thoughtful, Rightful and Lawful
Life
? Life is Journey of Realization
? Life is path to bring changes by corrections and
improvements
? Use Sense , Time and Energy for good significant
long-term outcome
? Adopt Do's of Health and Success
? Quit/Sacrifice don'ts with steadfastness for
prevention of Il -health and Failures
Let Al of Us Realize and Clearly Differentiate
? Do's and Don'ts of every human action
? Obedience and Disobedience
? Respect and Disrespect
? Truth and False
? Mistakes and Corrections
? Success and Failure
? Good and Bad
? Wrong and Right
? Healthy and Unhealthy
? Hygienic and Unhygienic
? Significant and Insignificant
? Helpful and Harmful
? Friend and Enemy
? Well wisher and Bad Wisher
? Patience and Impatience
? Gratitude and Thankless
? Blessings and Cursing's
Factors For Success
? Blessings
1. Selflessness/No Selfishness
2. Taking care equal y for oneself and
others
3. Obedience for truth and significant acts
4. Responsible and Dutiful
5. Being Truth and Transparent
6. Not making people wait /Lying
6. Not Cheating for our own benefits
7. Keeping and Fulfil ing Promises
8. Sharing of al good you have
9. Caring for one who needs
10. Spreading/Not Hiding significant
/true Knowledge
11. Not Distracting persons who are on
righteous path
12. Not Irritating one who is righteous
13. Lifting people who needs
14. Guiding for Right acts
15. Stopping from wrong acts
16. Not Hurting any soul with
disrespect and disobedience
17. Obeying and implementing true
words
18. Using best Sense, Energy and
Time for best long term outcome
S.No
8 Rs To Implement
1
Realize
2
Recapitulate
3
Reasoning
4
Reassess
5
Respond
6
Rehearse
7
Regular and Routine
8 4/4/2022
Rejuvenate
196
9 Ps Implement
9 Cs Implement
Prayers
Concentrate
Priorities
Communicate
Plan - Protocol
Cooperate
Practice
Commitment
Proof Read
Control
Perseverance
Coordinate
Positivity
Compensate
Patience
Companionship
Perfectionist
Cope up & Change
Best For Human Health
Thoughtfulness and Righteousness
Eating And Living Style
Natural-Planned ,Organized ,Regular , Disciplined
Simple , Humble, Care and Share
Yes for Good Stead Fast No For Bad
4/4/2022
198
Implement
Thoughtfulness and Righteousness
? Everywhere and Anywhere
? Every work and Any work
? Every time and Anytime
Tips Of Good Success
?Good Hard work
?Good Intentions
Live An Evidenced Based Life
? Acquire Knowledge- Search/Ask
(Do's and Don'ts of priority actions)
? Assess/Understand Truth
? Accept
? Apply/Implement -Truth/Dos
? Appraise/Evaluate its significance
? Spread Truth and Significance
THANKS
This post was last modified on 05 April 2022