Learning?
Biochemistry Of
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StarvationSpecific Learning Objectives
? What is Starvation?
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? Which Conditions develop Starvation?? What are Stages/Phases of Starvation?
? Which Hormones play imp role in starvation?
? Factors of Biochemical adaptation in Starvation
? How Organs adapt to Starvation?
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? What are Consequences of Starvation?What Is Starvation?
?Starvation is
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complete stoppageof eating food by a
human body.
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What Is Total Starvation?
?Total starvation is
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complete stoppageof Food and Water.
Conditions Developing Starvation
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Conditions Developing Starvation? Food Scarcity
(Natural Calamities , Draughts Floods and ,Famines)
? Extreme Poverty
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? Lost in Sea routes for long durations? Clinical Conditions: Major Surgeries, Severe Burns
? Desire to loose rapid weight
? Political Issues: Hunger Strikes
During
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Starvation
Body
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is underMetabolic Stress
Features Of Starved Body
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? No entry of exogenous food nutrients
? Starved body is deprived of:
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?Calories (Carbs and Lipids)?Building blocks (Proteins)
?Growth Factors(Vitamins and Minerals)
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?Protectors (Antioxidants)
Biochemical Adaptations
During Starvation
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Important Factors Responsible For
Adaptation In Starvation
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? Content Of Endogenous Stores? Health of Associated Organs and System
? Associated Metabolic Processes involved with:
?Hormones
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?Enzymes?Coenzymes
? During Starvation a body is in an
emergency/critical condition
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? Has to face Biochemical Chal enge
? Has to get adapted
? Manage with endogenous metabolite
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reserve stores? Communicate and Cooperate through
hormones
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?Overcome state by biochemical alterations
?Try Survive as per condition
Survival Period During Starvation
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? Survival period during Starvationdepends upon :
? Reserve TAG stores of Adiposecytes:
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?More content of TAG in Adiposecytes
?More is duration of survival in
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Starvation and vice a versa.Length Of Survival In Starvation
? Due to deprivation of only Food:
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?3 to 4 Weeks
?Longer up to 65 days
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? Deprivation of water alone thensurvival is only for few days
?Less than a week
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Effects Of StarvationOR
Human Body Adaptation In
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Starvation
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Biochemical Alterations InStarvation
Different Modes
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To Study Biochemical
Adaptations
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During Starvation PhasesStudy Of Biochemistry Of Starvation
With Respect To
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?Stages?Metabolism
?Organs
Alternative Adaptations
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In Different
Metabolic Processes
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During StarvationOccurrence Of
Four Stages During Starvation
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ORMetabolic Alterations During
Starvation
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Starvation
Metabolic Alterations
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Stages1
Increased Glycogenolysis
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2
Proteolysis
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Glucose Alanine CycleIncreased Gluconeogenesis
3
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Increased Lipolysis
Fatty acid Beta Oxidation(Incomplete)
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4Increased Ketogenesis
Ketosis
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Fasting ? Early Stage
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Muscle
Alanine / Pyruvate
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BrainGlucose
Glutamine
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Glycerol
Gluconeogenesis
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FatKetogenesis
Ketones
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AGL
Liver
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UreagenesisKetones
Urea
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NH3
Kidney
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IntestineFasting ? Late Stage
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MuscleAlanine / Pyruvate
Brain
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Glucose
Glutamine
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GlycerolGluconeogenesis
Fat
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Ketogenesis
Ketones
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AGLLiver
Ureagenesis
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Ketones
Urea
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NH3Kidney
Intestine
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Role Of Hormones In Starvation
? When food is in Short supply
? Metabolic activity decreases
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to spare fuel.? Conservation of energy is
basic adaptive response to
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calorie reduction
? Hormones influences an
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utilization of endogenousreserve stores and
? Supply fuels to body
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organs during starvation
phase.
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Hormonal Alterations In Starvation
? Insulin secretion
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decreased? Glucagon and Epinephrine
increased
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Metabolic Role Of Hormones
Hormonal Influences In Starvation
H ormone
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Source
Change in
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SecretionNorepinephrine Sympathetic
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Nervous System
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Norepinephrine Adrenal GlandEpinephrine
Adrenal Gland
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Thyroid
Thyroid Gland
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Hormone T4
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(changes to T3peripherally)
?Norepinephrine and T3
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participate to
?Decrease metabolic
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activity when calorie
intake decreases.
? Thus biochemical alterations during
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Starvation are influenced by hormonal
actions.
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? Glucagon and Epinephrine in starvationact upon target organs
? Stimulate metabolic pathways which
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supply fuels
? Improve survival phase during
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Starvation.Metabolic Alterations In Starvation
Biochemical Alterations Of
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Carbohydrate MetabolismDuring Starvation Phase
Carbohydrate Metabolism
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In Liver During Starvation Phase
? Glycogenolysis Increased
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? Glycogenesis Decreased? Glucose Alanine Cycle increased
? Gluconeogenesis Increased
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? Glycolysis Decreased
? TCA operation Decreased
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? HMP Shunt Decreased? Blood Glucose level Decreases (later stages)
? Cellular Glucose Deprivation (In Muscle Cells)
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?PDH a Multi Enzyme
Complex is inhibited
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during Starvation
Alterations In Protein Metabolism
During Starvation
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Proteins Serve as Calorific
During Starvation
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? Muscle Proteins are catabolized to providecarbon skeleton for Liver Gluconeogenesis
? Liver Gluconeogenesis increased via Glucose
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Alanine cycle regulates blood Glucose levels
? Glucose produced initially via Gluconeogenesis
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to Brain and ErythrocytesProtein Metabolism During Starvation
? As Glucose levels lowers in blood
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? Catabolism Of Muscle Proteinsincreased
? Transdeamination reaction of
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Amino acids is increased
? To release Glucogenic amino acids
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? Glucose Alanine Cycle elevates? Ammonia Detoxification and
Urea production increased
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initial y and decreased as
Starvation phase prolongs.
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? Body is in negative NitrogenBalance.
? Concentration of Functional
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Proteins Decreases.
Nitrogen Excretion in Starvation
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12
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ay
)
n
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(g
/d
8
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Normal Range
x
c
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re
t
io
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4Partial Starvation
N
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itr
o
g
e
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nE
Total Starvation
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010
20
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30
40
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DaysLong CL et al. JPEN 1979;3:452-456
Glucose Nitrogen Ratio
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Increased In Starvation
Biochemical Alterations of
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Lipid Metabolism In Starvation
Lipid Metabolism During Starvation
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? Lipolysis is Increased
? Mobilization of Free Fatty acids increased
? Beta oxidation of Fatty acids increased
? Incomplete Fatty acid Oxidation increased
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? Ketogenesis Increased? Ketolysis Decreased
? Ketosis Noted (Ketoacidosis)-Rotheras Test +ve
? Lipogenesis is Decreased
?Enzyme Acetyl Carboxylase
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is inhibited during
Starvation
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Levels Of Ketone BodiesIncreases
As
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Starvation Phase Prolongs
Increased Ketogenesis In Starvation
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What Happens? When Ketone body production
Exceeds than the Ketone body Utilization?
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? When Prolonged Starvation ?? Cellular Glucose deprivations occurs
? Glycogen stores depletes within 24 hrs of fasting
? Fat burns under flame of Carbohydrates
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? Fatty acid are incompletely oxidized? Acetyl-CoA of fatty acid oxidation is metabolized to
ketone bodies and mobilized out of Hepatocytes
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? Ketogenesis increased Ketolysis decreased? Leads to Ketosis-Ketonemia and Ketonuria
Prolonged Starvation Leads to
? Ketosis (Ketonemia and Ketonuria)
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? High levels of Ketone Bodies in blood and
urine
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? Ketoacidosis? Severe Ketosis
? Lowered blood pH
? Nausea ,Acetone breath
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? Coma, Death?3 days starvation
[Ketone Bodies]=3mM
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?3 weeks starvation
[Ketone Bodies]=7mM
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Cure For Ketosis
? Ketosis Cured by infusion of
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Glucose.During Starvation
Alterations Occur In
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Water and ElectrolyteAnd
Acid Base Balance
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? Reduction in Body Water
? Reduction of Potassium ions
? Acidic blood pH due to
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increased Ketone bodies?On prolonged phase of
Starvation there results
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?Severe dehydration andAcid Base imbalance
Starvation Alters BMR
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? BMR is first affected in starvation
? In starvation metabolism decreases
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? During starvation BMR is DecreasedBiochemical Adaptations
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By OrgansDuring Starvation Phase
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The Fasting State:Glucagon stimulates glucose
production and release in liver.
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Also mobilizes the fatty acids
(sparing Glucose for the Brain)
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FUEL CHOICE DURING STARVATION
1. Insulin
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6. Ketone bodies5. Fatty acids
2.Glucagon
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nge
3 .Glucose
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la
t
i
v
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echa
Re
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4. Glycogen
24
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Hours of StarvationChanges Of Liver Glycogen Content
During Starvation
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? Fuel changes from Glucose to Fatty acids toKetone bodies
Metabolic Response To Fasting
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Metabolic Response to Starvation is
Characterized
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? Switch from carbohydrate metabolism to fat
metabolism,
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? Context of a hypometabolic state, with minimizedcatabolism
? Initial y, stores of carbohydrate precursors (eg.
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glycogen) are depleted via Glycogenolysis within 24 hrs.
? In first 24-48 hours there is increased gluconeogenesis
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from amino acids and glycerol.? Subsequently, Ketogenesis takes over, and much of the
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body metabolic needs are met by ketone bodies andfree fatty acids.
? This is the consequence of decreasing insulin levels,
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and relatively increased influence from catecholamines
and cortisol.
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? Over prolonged starvation, protein catabolism begins,resulting in degradation of structural y important
proteins, and organ system dysfunction.
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Differentiation In
Well Fed And Fasting States
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Of Human Body
WELL-FED STATE
FASTING STATE
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Hormones
Insulin
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Glucagon,Adrenaline, Cortisol
Hyperglycemia
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Hypoglycemia
Response of
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GlycogenesisLipolysis
the body
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Lipogenesis
Ketogenesis
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Protein synthesisProteolysis
WELL-FED STATE
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FASTING STATE
Source of
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from stores(Glycogen)
Glucose
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from food
Gluconeogenesis
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Fate ofGlycolysis
Glucose
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formation of Glycogen and
Glycolysis
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TAG storesWELL-FED STATE
FASTING STATE
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Source offrom food TAG
from storage TAG
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Fatty acids
-oxidation
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Fate of Fatty-oxidation
(Incomplete one)
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acids
synthesis of TAG and
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Store as Depot FatKetogenesis
WELL-FED STATE
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FASTING STATE
Source of
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Amino acidsfrom food
From muscle Proteins
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Glucogenic amino
Fate of
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Protein synthesisacids
Amino acids
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Produce Glucose via
Gluconeogenesis
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Preferred fuels By Human body
In the Well-Fed and Fasting States
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OrgansWell-Fed
Fasting
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Liver
Glucose & Fatty
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Fatty acidsacids
Resting skeletal
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Glucose &
Fatty acids & KB
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MuscleFatty acids
Cardiac muscle
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Fatty acids
FA,AA & KB
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Adipose tissueGlucose
Fatty acids
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Brain
Glucose
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Glucose ,Later KBRBCs
Glucose
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Glucose
BIOCHEMICAL PROFILE OF EARLY FASTING STATE
Blood Glucose levels decreases
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65 mg/dl
Active Glycogenolysis
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Muscle and LiverShift of metabolic fuel from Glucose to fatty
acidsFatty acid mobilization from adipose tissues
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Gluconeogenesis
Glucose Alanine cycle
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BIOCHEMICAL PROFILE OF STARVED STATEGLUCOSE levels more decreased
40 mg/dL
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PROTEIN CATABOLISM increased
Sequesters Nitrogen as urea
Excretes 20 to 30 grams daily
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Gluconeogenesis taking place using precursors as
Amino acids
Lactate
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GlycerolKETONE BODIES increased
Acetyl CoA converted to ketone bodies via Ketogenesis
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In Prolonged Starvation? After 3 days of Starvation -> Liver
forms large amounts of Ketone
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bodies
( Due to shortage of Oxaloacetate)
? Ketone Bodies -> released into blood
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? Brain and Heart start to use ketonebodies as fuel during phase of
Starvation.
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Starvation Of Several Weeks
? After several weeks of starvation ->
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Ketone bodies become major fuel ofBrain
? After depletion of TAG stores
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? Proteins degradation accelerates? Death due to loss of Heart, Liver,
and Kidney function.
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Consequences Of Starvation
? Severe Nutrient deficiency
? Affects vitality and Damages Important
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Internal Organs /System? Anaemia (Iron and Protein deficiency)
? Decreased BMR
? Fatigue, Weakness
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? Low Immunity? Increases Sleep
? Night blindness (Vitamin A deficiency)
? Scurvy (Vitamin C deficiency)
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? Irregular Menses? Constipation
? Bone Loss
? Dehydration
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? Water Electrolyte Imbalance
? High Blood Pressure
? Brain Defects
? Coma and Death (Life Ends)
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Questions? Explain the different stages of
starvation & biochemical alterations
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in the body during these stages.
OR
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? Biochemical alterations/adaptationsduring starvation.
? Describe role of following
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organs during various stages ofstarvation
? Liver
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? Brain? Muscles
? Adipose tissues
THANK YOU
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Biochemistry