ENERGY METABOLISM
Dr.Katrin Roosita, MSi.
METABOLISME ENERGI……
Fig 1. METABOLISM
(Courtesy: Rimbawan, 2007)
Organ utama
pengaturan
metabolisme: hati,
jaringan lemak
(adipose), otot , dan
otak.
Peran: penyimpanan,
penggunaan dan
penyediaan sumber
energi (substrat).
SISTEM PENGATURAN
METABOLISME
Sistem Hormon
Sistem Saraf
Ketersediaan
Substrat
Hubungan
substrat – hormon- sistem
saraf
Substrat (glukosa dan protein)
mempengaruhi sekresi hormon
Hormon dan sistem saraf mengatur
metabolisme dan transport substrat.
HORMON UTAMA METABOLISME
http://www.medbio.info/Horn/PDF%20files/
homeostasis_2a.pdf
1 mmol/L = 18 g/dL
http://www.medbio.info/Horn/PDF%20files/homeostasis_2a.pdf
http://www.medbio.info/Horn/PDF%20files/homeostasis_2a.pdf
http://www.medbio.info/Horn/PDF%20files/homeostasis_2a.pdf
Penurunan Kadar glukosa darah & sekresi hormon
http://www.medbio.info/Horn/PDF%20files/homeostasis_2a.pdf
Fungsi insulin di sel target
en.wikipedia.org
http://www.medbio.info/Horn/PDF%20files/homeostasis_2a.pdf
CONTOH:
http://www.medbio.info/Horn/PDF%20files/homeostasis_2a.pdf
Aktivitas insulin di Sel Target
Ketersediaan Substrat
Berbeda antara kondisi:
- post absorpsi
- puasa/starvation
- olahraga berat
- terjadi gangguan metabolisme dan kondisi
sakit.
ABSORPTIVE STATE
2 - 4 HOURS period after
ingestion of a normal meal :
ABSORPTIVE STATE
INCREASES in plasma glucose, amino acids, and
triacylglycerols
baby-growths.com
lipogenesis
MECHANISMS OF HEPATIC- AMINO ACID
METABOLISM (in the absorptive period)
The surplus amino acids ARE NOT STORED, but are either:
a. released into the blood for all tissues to use in
protein synthesis,
b. they are with the resulting carbon skeletons being
degraded by the liver pyruvate, acetyl CoA, or TCA
cycle intermediates, these metabolites can be
oxidized for energy or used in fatty acid synthesis.
METABOLISM OF
ADIPOSE TISSUE
in Absorptive State
A. Carbohydrate metabolism
1. Increased glucose transport
2. Increased glycolysis:.
3. Increased activity in the hexose monophosphate (HMP) pathway.
B. Fat Metabolism
1. Increased synthesis of fatty
acids.
2. Increased triacylglycerol
synthesis
3. Decreased triacylglycerol
degradation
METABOLISM OF RESTING MUSCLE
in absorptive State
1. Increased glucose transport
2. Increased glycogen synthesis3. Increased protein synthesis4. Increased uptake of branched-chain amino acids.
METABOLISM OF BRAIN IN
ABSORPTIVE STATE
http://www.medbio.info/Horn/PDF%20files/homeostasis_2a.pdf
Copyright 2009, John Wiley & Sons, Inc.
Principal metabolic pathways during the
absorptive state
AMINO ACIDS GLUCOSE TRIGLYCERIDES
(in chylomicrons)
Blood
GLUCOSE
GASTROINTESTINALTRACT
+ H2O +CO2
MOST TISSUES
Oxidation
ATP
1
AMINO ACIDS GLUCOSE TRIGLYCERIDES
(in chylomicrons)
Blood
GLUCOSE
GASTROINTESTINALTRACT
HEPATOCYTES IN LIVER
+ H2O +CO2
MOST TISSUES
Oxidation
ATP
Fatty acids
Triglycerides
Glyceraldehyde
3-phosphateGlycogen
Glucose
+ H2O +CO2 ATP
1
2
AMINO ACIDS GLUCOSE TRIGLYCERIDES
(in chylomicrons)
Blood
GLUCOSE
GASTROINTESTINALTRACT
HEPATOCYTES IN LIVER
+ H2O +CO2
MOST TISSUES
Oxidation
ATP
Triglycerides
ADIPOSE TISSUE
VLDLs
Triglycerides
Fatty acids
Triglycerides
Glyceraldehyde
3-phosphateGlycogen
Glucose
+ H2O +CO2 ATP
1
2
3
AMINO ACIDS GLUCOSE TRIGLYCERIDES
(in chylomicrons)
Blood
GLUCOSE
GASTROINTESTINALTRACT
GLUCOSE
HEPATOCYTES IN LIVER
SKELETAL
MUSCLE
Storage
+ H2O +CO2
MOST TISSUES
Oxidation
ATP
Triglycerides
ADIPOSE TISSUE
VLDLs
Fatty
acids
Triglycerides
Glyceraldehyde
3-phosphate
Glucose
Fatty acids
Triglycerides
Glyceraldehyde
3-phosphateGlycogen
Glucose
GlycogenGlycogen
+ H2O +CO2 ATP
1
2
3
4
4
AMINO ACIDS GLUCOSE TRIGLYCERIDES
(in chylomicrons)
Blood
GLUCOSE
GASTROINTESTINALTRACT
GLUCOSE
HEPATOCYTES IN LIVER
SKELETAL
MUSCLE
Storage
+ H2O +CO2
MOST TISSUES
Oxidation
ATP
Triglycerides
ADIPOSE TISSUE
VLDLs
Triglycerides
Fatty
acids
Triglycerides
Glyceraldehyde
3-phosphate
Glucose
Fatty acids
Triglycerides
Glyceraldehyde
3-phosphateGlycogen
Glucose
GlycogenGlycogen
+ H2O +CO2 ATP
1
2
3
4 5
4
AMINO ACIDS GLUCOSE TRIGLYCERIDES
(in chylomicrons)
Blood
GLUCOSE
GASTROINTESTINALTRACT
GLUCOSE
HEPATOCYTES IN LIVER
SKELETAL
MUSCLE
Storage
+ H2O +CO2
MOST TISSUES
Oxidation
ATP
Triglycerides
ADIPOSE TISSUE
VLDLs
Triglycerides
Fatty
acids
Triglycerides
Glyceraldehyde
3-phosphate
Glucose
Keto acids
Fatty acids
Triglycerides
Glyceraldehyde
3-phosphateGlycogen
Glucose
GlycogenGlycogen
+ H2O +CO2 ATP
1
2
3
4 5
6
4
AMINO ACIDS GLUCOSE TRIGLYCERIDES
(in chylomicrons)
Blood
GLUCOSE
GASTROINTESTINALTRACT
GLUCOSE
HEPATOCYTES IN LIVER
SKELETAL
MUSCLE
Storage
+ H2O +CO2
MOST TISSUES
Oxidation
ATP
Triglycerides
ADIPOSE TISSUE
VLDLs
Triglycerides
Fatty
acids
Triglycerides
Glyceraldehyde
3-phosphate
Glucose
Keto acids
Fatty acidsProteins
Triglycerides
Glyceraldehyde
3-phosphateGlycogen
Glucose
GlycogenGlycogen
+ H2O +CO2 ATP
1
2
3
4 5
6
7
4
AMINO ACIDS GLUCOSE TRIGLYCERIDES
(in chylomicrons)
Blood
GLUCOSE
GASTROINTESTINALTRACT
GLUCOSE
HEPATOCYTES IN LIVER
SKELETAL
MUSCLE
Storage
+ H2O +CO2
MOST TISSUES
Oxidation
ATP
Triglycerides
ADIPOSE TISSUE
VLDLs
Triglycerides
Fatty
acids
Triglycerides
Glyceraldehyde
3-phosphate
Glucose
Keto acids
Fatty acidsProteins
Triglycerides
Glyceraldehyde
3-phosphateGlycogen
Glucose
GlycogenGlycogen
ProteinsProteins
+ H2O +CO2 ATP
1
2
3
4 5
6
7
8
4
Copyright 2009, John Wiley & Sons, Inc.
Metabolism during postabsorptive state About 4 hours after the last meal absorption in
small intestine nearly complete
Blood glucose levels start to fall
Main metabolic challenge to maintain normal blood glucose levels
Glucose production
Breakdown of liver glycogen, lipolysis, gluconeogenesis using lactic acid and/or amino acids
Glucose conservation
Oxidation of fatty acids, lactic acid, amino acids, ketone bodies and breakdown of muscle glycogen
Copyright 2009, John Wiley & Sons, Inc.
Principal metabolic pathways during the
postabsorptive state
1
Liver glycogen
Glucose
LIVER
Blood
HEARTADIPOSE TISSUESKELETAL MUSCLE TISSUE
OTHER TISSUES
1
Liver glycogen
Glucose
LIVER
Glycerol
Blood
HEART
Fatty acidsGlycerol
TriglyceridesADIPOSE TISSUE
SKELETAL MUSCLE TISSUE
OTHER TISSUES
2
Fatty acids
1
Liver glycogen
Glucose
LIVER
Lactic acid
Glycerol
Blood
HEART
Fatty acidsGlycerol
TriglyceridesADIPOSE TISSUE
SKELETAL MUSCLE TISSUE
OTHER TISSUES
3
2
Fatty acids
1
Liver glycogen
Keto acids
Glucose
Amino acids
LIVER
Lactic acid
Glycerol
Blood
HEART
Muscle proteins
Fatty acidsGlycerol
TriglyceridesADIPOSE TISSUE
Fasting or
starvation
SKELETAL MUSCLE TISSUE
OTHER TISSUES
ProteinsAmino acids
Amino acids
4
4
3
4
2
Fatty acids
1
Liver glycogen
Keto acids
Glucose
Amino acids
LIVER
Lactic acid
Glycerol
Blood
HEART
Fatty acids
Muscle proteins
Fatty acidsGlycerol
TriglyceridesADIPOSE TISSUE
Fasting or
starvation
SKELETAL MUSCLE TISSUE
OTHER TISSUES
Fatty acids
ProteinsAmino acids
Amino acidsFatty acids
ATP
ATP
ATP
4
5
5
4
3
5
4
2
Fatty acids
1
Liver glycogen
Keto acids
Glucose
Amino acids
LIVER
Lactic acid
Glycerol
Blood
HEART
Fatty acids
Muscle proteins
Fatty acidsGlycerol
TriglyceridesADIPOSE TISSUE
Fasting or
starvation
SKELETAL MUSCLE TISSUE
OTHER TISSUES
Fatty acids
ProteinsAmino acids
Amino acidsFatty acids
Lactic acid
ATP
ATP
ATP
ATP
4
5
5
6
4
3
5
4
2
Fatty acids
1
Liver glycogen
Keto acids
Glucose
Amino acids
LIVER
Lactic acid
Glycerol
Blood
HEART
Fatty acids
Muscle proteins
Fatty acidsGlycerol
TriglyceridesADIPOSE TISSUE
Fasting or
starvation
SKELETAL MUSCLE TISSUE
OTHER TISSUES
Fatty acids
ProteinsAmino acids
Amino acidsFatty acids
Lactic acid
ATP
ATPATP
ATP
ATP
4
5
5
67
4
3
5
4
2
Fatty acids
1
Liver glycogen
Keto acids
Glucose
Amino acids
LIVER
Fatty acids
Lactic acid
Ketone bodies
Glycerol
Blood
NERVOUS
TISSUE Ketone
bodies
Glucose
Starvation
HEART
Fatty acids
Muscle proteins
Fatty acidsGlycerol
TriglyceridesADIPOSE TISSUE
Fasting or
starvation
SKELETAL MUSCLE TISSUE
Ketone bodies
OTHER TISSUES
Fatty acids
ProteinsAmino acids
Amino acidsFatty acids
Ketone bodies
Lactic acid
ATP
ATP
ATP
ATP
ATP
ATP
ATP
ATP
ATP ATP
4
5
8
5
6
88
7
4
3
5
4
2
8
1
Liver glycogen
Keto acids
Glucose
Amino acids
LIVER
Fatty acids
Lactic acid
Ketone bodies
Glycerol
Blood
NERVOUS
TISSUE Ketone
bodies
Glucose
Starvation
HEART
Fatty acids
Muscle proteins
Fatty acidsGlycerol
TriglyceridesADIPOSE TISSUE
Fasting or
starvation
SKELETAL MUSCLE TISSUE
Ketone bodies
OTHER TISSUES
Fatty acids
ProteinsAmino acids
Glucose
6-phosphate
Pyruvic acid
Lactic
acid
Muscle glycogen
(aerobic) (anaerobic)
Amino acidsFatty acids
Ketone bodies
Lactic acid
ATP
O2
ATP
ATP
ATP
ATP
ATP
ATP
ATP
ATP
ATP
ATP ATP
+ O2–
4
5
8
5
6
88
7
4
3
9
5
4
2
8
FASTING METABOLISM
Fasting
a. an inability to obtain food,
b. the desire to lose weight rapidly,
c. in clinical situations in which an individual cannot eat because of trauma, surgery, burns, and so forth.
Physiology of Fasting: the absence of food, plasma levels of glucose, amino acids, and triacylglycerols fall, triggering a decline in insulin secretion and an increase in glucagon release.
This sets into motion an exchange of substrates between
liver, adipose tissue, muscle, and brain :
1. the need to maintain adequate plasma levels of glucose
to sustain energy metabolism of the brain and other
glucose-requiring tissues.
2. the need to mobilize fatty acids from adipose tissue, and
the synthesis and release of ketone bodies from the
liver, to supply energy to all other tissues.
INSULIN / GLUCAGON RATIO
availability of circulating substrates
CATABOLIC PERIOD: by degradation of triacylglycerol, glycogen, and protein.
Diseases and Blood Sugar
Regulation Elevated glucose levels are present in diabetes mellitus,
Cushing's syndrome, liver disease, and hyperthyroidism.
Decreased glucose levels are present in Addison's disease, hyperinsulinism, and hypothyroidism.
The most prevalent of these diseases is diabetes mellitus (DM).
Type I DM (insulin-dependent or juvenile-onset) diabetes mellitus, when pancreatic beta cells are destroyed by an erroneous attack by the body's own immune system.
Type II DM, insulin secretion is not reduced; however, there is a reduced sensitivity of target cells to insulin, a phenomenon known as insulin resistance. (Paul I, 2007).
Overview and Specificity:
Glucose utilization
Stage 1 – postparandial
All tissues utilize glucose
Stage 2 – postabsorptive
KEY – Maintain blood glucose
Glycogenolysis
Glucogneogenesis
Lactate
Pyruvate
Glycerol
AA
Propionate
Spare glucose by metabolizing fat
Stage 3- Early starvation
Gluconeogenesis
Stave 4 – Intermediate starvation
gluconeogenesis
Ketone bodies
Stage 5 – Starvation
Carbohydrate Metabolism/
Utilization- Tissue Specificity Muscle – cardiac and skeletal
Oxidize glucose/produce and store glycogen (fed)
Breakdown glycogen (fasted state)
Shift to other fuels in fasting state (fatty acids)
Adipose and liver
Glucose acetyl CoA
Glucose to glycerol for triglyceride synthesis
Liver releases glucose for other tissues
Nervous system
Always use glucose except during extreme fasts
Reproductive tract/mammary
Glucose required by fetus
Lactose major milk carbohydrate
Red blood cells
No mitochondria
Oxidize glucose to lactate
Lactate returned to liver for Gluconeogenesis
Terima kasih atas
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REFERENCES
http://www.medbio.info/Horn/PDF%20files/homeostasis
_2a.pdf. Insulin_Glucagon Role in Metabolism.pdf
Tom Brody. Nutritional Biochemistry, 2nd edition,
Academic Press, 1999
Pamela C. Champe & Richard A. Harvey
Biochemistry, 2nd edition, J.B. Lippincott Company,
Philadelphia, 1994.
Illingworth. 2007. Biochemistry for Biologists
Fitness Training.
www.bmb.leeds.ac.uk/.../bioc1110/index.htm .
Rimbawan, 2007. Metabolism Slides
Molecular mechanisms of insulin signaling.
Rask-Madsen C , and Kahn C R Arterioscler Thromb Vasc Biol. 2012;32:2052-2059
Copyright © American Heart Association, Inc. All rights reserved.
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