METABOLISM th - lms.ipb.ac.id · 5/3/2017 MATERI AJAR FISIOLOGI VETERINER II (METABOLISME) 59 Lipid Metabolism Lipid is particularly stored in the adipose tissue - The fatty acids

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METABOLISM

DIVISION OF PHYSIOLOGY

DEPARTMENT OF ANATOMY, PHYSIOLOGY ANDPHARMACOLOGY

FACULTY OF VETERINARY MEDICINE IPB

5/3/2017 MATERI AJAR FISIOLOGI VETERINER II (METABOLISME) 1 5/3/2017 MATERI AJAR FISIOLOGI VETERINER II (METABOLISME) 2

References:

1. Cunningham’s Textbook of Veterinary Physiology 5th edition; Elsevier, pp 342-358

2. Clinical Anatomy and Physiology for Veterinary Technicians 3rd edition (Colville and Bassert), pp 417-444

3. Dee Unglaub Silverthorn Human Physiology An Integrated Approach, pp 739-765

5/3/2017 MATERI AJAR FISIOLOGI VETERINER II (METABOLISME) 3

Foundation of nutrition and cell metabolism


Metabolism

Metabolism

anabolism

catabolism

Metabolism: the sequence of reaction or succession of a chemical

processes that occur in the living organisms

Anabolism: synthesis of complex compounds from simple molecules,

example: the formation of glycogen from glucose

(glycogenesis); lipogenesis, protein synthesis,

Catabolism: breakdown of complex compounds into more simple

materials.for example: glycolysis, lipolysis, breakdown of

nutrients into CO2 + H2O + energy, etc

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Catabolism of food energy production

Essential for: - Maintaining body functions

- Digestion

- Metabolism

- Thermoregulation

- Physical activities


Energy Transfer:

HS - Ko-A + as. Asetat asetil ko-A (reduced Ko-A)

- Energy produced by catabolism process is utilized for the formation of :

- Energy-rich phosphate compounds

ATP, hydrolized into ADP & AMP

Creatine phosphate

GTP (guanosine triphosphate)

CTP (cytidine triphosphate)

UTP (uridine triphosphate)

ITP (inosine triphosphate)

• Kelompok tio-ester : Koenzim-A (Ko-A)


ATP and Energy Transfer Cells

In the cell, energy from the catabolism process will be transferred into ATP

• Hydrolysis ATP into ADP and P will release energy which is then used for cell activity

• ATP + H2O ADP + P + 7 kcal/mol


First Law Thermodinamic :

Energy can not be formed nor destroyed, but

can be converted

Δ E = H + W

60 % 40 %

ATP

Total energy produced = The heat generated by the

body + work + energy stored

Δ E = released energy

H = heat

W = energy for work (transport,

mechanical and chemical

process)

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HEAT ENERGY 60%

Food molecules

(Carbohydrate,

Protein or Fat)

CO2 + H2O + NH3

Catabolism

CHEMICAL ENERGY 40%

ADP + P ATP

Energy used for cell functions: (1) Power and movement, (2) Membrane

Transport, (3) Molecule Synthesis


Absorptive vs Post Absorptive


Metabolic Pathway During Absorptive


Metabolic Pathway During Post Absorptive

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Measured under the conditions:

- Resting

- Thermoneutral

- Post absorptive (12-14 hrs after meal)

Energy Balance

Balance between calory intake and & energy produced

If - catabolism of energy sources (endogenous)

If + energy will be stored and the individu will gain

weight

Basal Metabolic Rate (BMR)


• The amount of energy / heat produced per unit time

• Energy is stored in the form of rich-energy

compounds (ATP, GTP, ADP, etc.)

• The unit of energy/heat measurement: kilocalori (K)

Definition : the amount of heat required for

increasing the temperature of 1 gr of water as much

as 1oC

Metabolic Rate

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- Energy measurement:

o Direct Calorimetry (equipped with climate chamber

bomb calorimeter )

o Undirect Calorimeter

- O2 consumption

- CO2 production}RQ (Respiratory Quotient): CO2 prod/ O2 cons


Nutrient Respiratory Quotient

Carbohydrates 1

Proteins 0.8 - 0.9

Ketones (eucaloric) 0.73

Ketones (hypocaloric) 0.66

Triolein (Fat) 0.7

Oleic Acid (Fat) 0.71

Tripalmitin (Fat) 0.7

Malic acid 1.33

Tartaric acid 1.6

Oxalic acid 4.0


Bomb calorimeter

http://image.wistatutor.com/content/feed/tvcs/image1_27.jpg


Measurement of Metabolic Rate with Heat Production

Correlation

https://en.wikipedia.org/wiki/Carbohydrates

https://en.wikipedia.org/wiki/Proteins

https://en.wikipedia.org/wiki/Ketones

https://en.wikipedia.org/wiki/Ketones

https://en.wikipedia.org/wiki/Triolein

https://en.wikipedia.org/wiki/Oleic_Acid

https://en.wikipedia.org/wiki/Tripalmitin

https://en.wikipedia.org/wiki/Malic_acid

https://en.wikipedia.org/wiki/Tartaric_acid

https://en.wikipedia.org/wiki/Oxalic_acid

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Measurement of Metabolic Rate with Oksigen Consumption

Correlation


Factors influenced metabolic rate:

- Muscular activities

- Food ingesti

- Environment temperature

- Height, weight and body surface area

- Sex

- Age

- Emotional state

- Body temperature

- Blood thyroid level

- Blood Epinephrine/norepinephrine level


Control of Food Intake

“Satiety signals” receptor hungry

satiety

Involved plasma glucose level & hormone which regulate organic

compound metabolism (carbohydrate and fat)

Hormone that regulate metabolism :

- Insulin

- Glukagon

- GH

- Glucocortikoid

- Epinephrine

- Tyroxine no effect

Glucose


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Source of carbohydrate


Absorptive Phase: Carbohydrate

Insulin stimulant: gastric inhibitory peptide

Storage of glucose by the liver glicogen and TG

Glucose glicogen

Glucose fatty acid via glycolysis 2 pyruvate acids acetil co-A Krebs cycle + oxaloacetate citrate to cytosol fatty acid

Glucose fatty acid (irreversible)

Krebs Cycle or Citric Acid Cycle (CAC) – also known as the Tricarboxylic Acid (TCA) cycle


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1. Aerobic catabolism through the glycolytic pathway would produce pyruvic acid and enter the Krebs cycle

In aerobic condition 38 molecules of ATP

produced, which 34 are from

oxidative phosphorylation, 2 ATP from

glycolysis and 2 ATP from the Krebs cycle

In anaerobic condition 2 molecules of ATP

produced

40% of energy from glucose under aerobic

conditions is transferred to ATP and the

remainder for heat production

Carbohydrate Catabolism


GLYCOLYSIS

The group of phosphate is moved from metabolic phosphorylation to ADP. Substratephosphorylation generally occurs in the glycolytic pathway in which the enzyme involved is in the cytosol

Glucose + 2ADP + 2Pi

2 lactic acid + 2 ATP + 2 H20

Carbohydrates are the materials that can only be entered into the glycolytic pathway:

- Aerobic ATP and pyruvic acid

- Anaerobic ATP and lactic acid


Glycolysis

Utilyzes

2 ATP

Produces: 4 ATP

Glycolysis produces:

• (4 - 2) = 2 ATP

• 2 pyruvic acid

• 2 NADH


Anaerobic Glycolysis

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Cellular Respiration


Krebs Cycle

Krebs Cycle

produces :

• 1 ATP

• 3 NADH

• 1 FADH2


Biological oxidation

- Oxidation: reaction of compounds + O2 (loss of H +, e-)

- >< Reduction

- Oxidation is catalyzed by catalytic enzyme

Oxidative phosphorylation

- The formation of ATP through a process of oxidation by flavoproteins and cytochrome enzymes


Oxidative phosphorylation

Reactions involving two H atoms combined with oxygen to form water

Occurs in the inner membrane of the mitochondria as the forming enzyme is in the mitochondria

H+ is obtained from catabolism of food and transferred to the mitochondria as coenym-2H

Coenzym-2H + ½ O2

Coenzym + H2O + 52 kcal/mol

The main source of ATP

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Oxydative Phosphorilation



• Carbohydrates are stored in the form of

glycogen mainly in the liver and

skeletal muscle

• Glucose can be synthesized from the

amino acid, pyruvic acid and glycerol.

• Lactic acid can not be synthesized into

glucose except in the liver.

Carbohydrate metabolism

(continued)


Cell Membrane

Blood

Glucose

Uridine diphosphate

glucose

Glycogen

Glucose-1-P

Glucose-6-P

Glycolysis

glucokinase/hexokinase

Glucose

phosphatase

phosphorylase

Glycogenesis and Glycogenolisis

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Synthesis of glucose to glycogen


Glucose phosphorylation is irreversible

except in the liver cells, renal tubular

epithelial cells, and intestinal epithelial

cells because of the presence of glucose

phosphatase enzyme

Oxidation of 1 gram of glucose molecule

produces energy as much as 686.000

calories

Formation of 1 gram of ATP molecule needs

12.000 calories breakdown of glucose

produces 38 mol ATP


Breakingdown of glycogen into glucose:

glycogenolysis

Activation of phosphorylation is stimulated by

epinephrine and glucagonAMP cyclic

The release of energy from glucose glycolysis

(produces two molecules of pyruvic acid)

38 molecules of ATP

The release of energy from glucose can be via

Glycolysis pathway (Embden Meyerhof)

Pentose phosphate pathway

(Phosphogluconate)


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GLYCOGENESIS- From glucose- From lactic acid, glycerol, pyruvic acid,

and some deaminated amino acids glucose glycogen

GLYCOGENOLYSIS- Phosphorylation phosphorylase enzyme- Activated by epinephrine and glucagon AMP cyclic

GLYCOLYSIS- Releasing of energy from glucose molecule

GLUCONEOGENESIS- Occurs in the liver, and some in the kidney


Regulation of energy release from glycogenolysis glycolysis

1. Inhibition to the enzyme phosphofructokinase by ATP inhibits theformation of fructose 1,6-phosphatase

2. Inhibits by citrate ions3. The mechanism of the ATP-ADP-AMP


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LIPID : - Triglyceride (neutral fat) - Phospholipid- Cholesterol

Triglyceride (TG) : long chain fatty acids + glycerol

- Stearate acid (C 18, saturated) - Oleic acid (C16, unsaturated) - Palmitic acid (C16, saturated)

LIPID


Saturated Fatty Acid


Unsaturated Fattyu Acid


LIPID

Triglyceride source of energy

PhospholipidCholesterol } Cell Membrane

Triglyceride as energy 146 mol ATP

The amount of ATP formed from 1 gr of lipid is 2,5 times of ATP formed from 1 gr of carbohydrate

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Digestion of TG fatty acid + glycerol

chylomicron (small droplet of TG), apoB

enter the limph vessel


Hydrolysis of chylomicrons by LPL (lipoprotein lipase) in the adipose tissues and the liver fatty acid and glycerolthen synthesis of TG again in theliver and adipose cells

When it is needed for energyTG from adipose tissue or fat deposit is

transported to other tissues in the form of free fatty acids or non-esterified fatty acid bound to albumin

Controls: - Glucose levels in adipose cells -

glycerophosphate hydrolysis of TG- Hormones that increase hydrolysis of TG


LIPOPROTEIN

Composition : TG, cholesterol, phospholipidand protein

It is syntesized in the liver Function : lipid transport in the blood Types :

- VLDL TG, cholesterol and phospholipid are moderate

- IDL TG , cholesterol and phospholipid >>

- LDL no TG, cholesterol , phospholipid is moderate

- HDL protein , cholesterol and phospholipid <<

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Lipid Metabolism Lipid is particularly stored in the adipose tissue

- The fatty acids are broken down in the mitochondria and enter the Krebs cycle

- Fatty acid binds to glycerophosphate to form triacylglycerol


TG for energy production :- Hydrolisis of TG fatty acid and dan glycerol- Transport to the tissues oxiidation- Glycerol glycerol 3-phosphat enter the glycolytic pathway

Stages: Transports of fatty acid into the mitochondria

carnitine carrier Beta oxidation conversion of fatty acid into acetyl CoA Oxidation of acetyl-CoA in the Krebs cycle Final result is 146 molecules of ATP

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Lypolysis


Lypolysis


Keton Bodies:- Acetoacetic acid (keto acid)- -hydroxybutyric acid- Acetone

increase in the condition of hunger, diabetes

If ketosis


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Formation of TG from Carbohydrate Irreversible Started with glycolysisConversion of glucose to acetyl-coACitrate is transported into cytosol Needs insulin


Protein

Amino acid is the final product of protein digestion


MATT HILL PVMethionin Arginin Tryptophan Treonine Histidin

Isoleusin Lysin Leusin Phenylalanin Valine


Protein Metabolism

Anabolisme protein synthesis

Catabolism

Amin group will be eliminated from the amino acids and will form a keto acid which can then be catabolized to generate energy that is then transferred to the ATP or can be synthesized into fatty acids

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General Protein metabolism pathway


Amin group will be eliminated from the amino acid by way of:

Oxidation deamination, which would produceammonia. Ammonia formed is then converted into urea in the liver and excreted through the kidneys

Transamination, in which the amine group will be transferred to the keto acids and to form new amino acids

Protein Catabolism


Deamination dan Transamination


Protein Catabolism

- Free amino acid is stored in the form of cellular protein, and will undergo catabolism in most tissues, especially in the intestinal

mucosa, liver, skeletal muscle, kidney and brain.

- Lysin and Leusin form non-gluconeogenic intermediate products

- Protein catabolism process will particularly release amine group α-keto acids oxidation CO2

ATP formation

Glucose and lipid synthesis

- Cellular protein amino acid by enzyme: intracellularlysosome

- Exception: protein in the nucleic chromosome structural protein (collagen and contractile protein)

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In the liver, amino acids undergo deamination process released of amine group and the formation of keto-analog enter carbohydrate metabolism pathway


- Released NH3 is converted to ureum and excreted (in mammals)

- In the reptile and birds NH3 is converted to uric acid

- In the aquatic species N waste is excreted in the form of ammonium ion

Oxidation and deamination of amino acid

- Deamination products : -keto acidenter siklus Krebs oxidation energy

Ureum formation by the liver- Deamination ammonia (NH3) ureum


Formation and excretion of urea is a main waste product of N from protein catabolism


Protein Metabolism in the Liver

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The main metabolic fuel components:

• Glucose (stored in the form of glycogen, in the liver and muscle)

• Amino acid (stored in the form of muscle protein)

• Fatty acid (3 fatty acids+1 glycerol in ester bond, stored in the form of TG in the adipose tissue)

• Keton bodies: acetone, acetoacetic acid,

-hydroxybutiric acid (from the fatty acid)


Functional State in the Regulation of Metabolism

1. Absorptive stage: Stage where the nutrients from the digestive tract enterthe bloodstream

2. Post-absorptive stage: stage where the digestive tract is of nutrients so that the energy is taken from the storage


NUTRIENT REQUIREMENT AT THE STAGE OF ABSORPTION


In the absorption phase, liver takes up the glucose and converts it into glycogen and TG

Transport of fatty acid out side the cell as Very Low Density Lipoprotein (VLDL)

Circulation of amino acid in the blood is regulated by the liver

The fate of amino acid in the liver:

1. Is utilized for protein synthesis

2. Is converted into the form of analog carbohydrate and enter the Krebs cycle

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Influence of diet on insulin and glucagon

Insulin Glucagon

Carbohydrate + -

Protein + +


Nutrients Requirement in

Post-absorptive Stage


Post-absorptive Phase

• Glucagon, Insulin ↓

• Hormone-sensitive lipase (HSL) release of fatty acid from the adipose tissue

• HSL is active because of insulin secretion is decrease in the phase of post-absorptive(Insulin stimulates dephosphorylation) and cathecolamine secretion

• Final product: Free fatty acid = Non Esterified Fatty Acid (NEFA)


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BCAA: Branch-Chain Amino Acid

(Valine, Leucine, Isoleucine)

Amino acid of muscle origin as a source of

glucose



Source of blood glucose :

1. Glycogenolysis (glycogen breakdown)

2. Gluconeogenesis (synthesis of glucose from lipidand protein)

SOURCE OF ENERGY DURING LACK OF FOOD:

fatty acid, triglyseride and keton bodies


In the state of satrving/ fasting

- Fast mobilization of the NEFAs to the liver

• Oxidation for energy production

• Esterification TG production

• Ketone bodies production

In the liver mitochondria + carnithineBut depending on the existence of : CPT 1 (carnitine palmitoyl transferase I) enzyme

Is inhibited by malonyl CoA

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Starvation:

1. Phase 1- Decreased of LMB- The source of glucose comes from liver

glycogen (depleted in a matter of hours)- Next energy sources: fat catabolism (fatty

acids and glycerol) and amino acids glucose

- Production of ketone bodies2. Phase 2

• After 1 – 2 weeks, brain and other tissues utilize glucose and ketone bodies

• The main source of energy comes from the lipid


Starvation:

Phase 3• Protein as a energy source (the liver, plasma protein,

then protein in the GI tract, liver and the muscle)• Decreasing of the size and function of the organ• Decreasing of the plasma protein decreasing of the

oncotic pressure ascites

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RUMINANTS

• Supply of glucose is from the gluconeogenesis(propionate VFA succinate oxaloacetate Krebs cycle)

• Acetate and butiric acid acetil ko-A Krebscycle unable to form oxaloacetate or glucose


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Endocrine and Nerve System Regulation in the

Phase of Absorption and Post-absorption

1. Insulin

Is an amino acid and is secreted by the βcell of pancreas

High plasma glucose stimulates insulinsecretion

Insulin action:

1. Increases cell membrane ability to uptake glucose

2. Increases enzyme function


Effect of Insulin on carbohydrate metabolism

Increases glucose uptake by the cells (T)

Stimulates glycolysis (E)

Stimulates glycogen synthesis (E)

Inhibits of glycogen catabolism (E)

Inhibits gluconeogenesis (E)

Resuts :

Decreasing of plasma glucose concentration, increasing glycogen storage

Increasing glucose uptake compared to the releasing of glucose from the liver


Effect of Insulin on Lipid Metabolisme

Stimulates TG synthesis (E)

Inhibits TG catabolism (E)

Stimulates lipoprotein lipase in the endothelial cells (E)

Results :

Decreasing of plasma glycerol and free fatty acid concentration

Increasing of fat storage and decreasing of the utilization of fat for energy


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2. Glucagon

Is an amino acid and is secreted by the αcell of pancreas

Regulation of glucagon secretion:

1.Low of plasma glucose

2.High of plasma amino acid

3. Activation of sympathetic nerve and ephinephrine in the circulation

4.Inhibition of parasympathetic nerve

5.Other hormones (GH, cortisol etc)



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3. Epinephrine and sympathetic nerve to the

liver and adipose tissues

Plasma Glukosa

Adrenal medula

Sekresi Epinefrin

Plasma Epinefrin

Otot Rangka

Glikogenolisis

Asupan Glukosa

Plasma Glukosa, asam lemak, gliserol

Aktivitas saraf simpatis

menuju jaringan lemak dan

hati

Hati

Glikogenolisis

Glukoneogenesis

Jaringan lemak

Lipolisis

Reflex melalui reseptor

glukosa pada otak


4. Cortisol

Efffect of cortisol on the metabolism:

1. Basal concentration of cortisol is a stimulant forgluconeogenesis and lypolysis in the phase of post-absorptive

2. The increase of cortisol concentration will cause:

a. Increasing of protein catabolism

b. Increasing of gluconeogenesis

c. Decreasing of glucose uptake by the cells

d. Increasing of TG breakdown

Results: Increasing plasma amino acid, glucose and free fatty acid


5. Growth Hormone

Function:

1. Stimulates lypolysis in the adipose tissues

2. Increases gluconeogenesis by the liver

3. Decreasing glucose uptake by the tissues

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GLUCOSE REGULATION

Glucagon Epinephrine Cortisol GH

Glycogenolysis X X

Gluconeogenesis X X X X

Lypolysis X X X X

Inhiition of

glucose upotakeX X X

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METABOLISM th - lms.ipb.ac.id · 5/3/2017 MATERI AJAR FISIOLOGI VETERINER II (METABOLISME) 59 Lipid Metabolism Lipid is particularly stored in the adipose tissue - The fatty acids