Metabolisme dan

Termoregulasi
Muhammad Iqbal
Metabolisme KH dan Pembentukan ATP

Release of Energy From Foods and“Free Energy”

energy : f muscle activity, secretion by the glands, maintenance of
membrane potentials by the nerve and muscle fibers, synthesis of
substances in the cells, absorption of foods from the GI tract, and many
other functions.
• Coupled Reactions. All the energy foods—carbohydrates,fats, and
proteins—can be oxidized in the cells, and during this process, large
amounts of energy are released.
To provide this energy, the chemical reactions must be “coupled” with the
systems responsible for these physiologic functions. This coupling is
accomplished by special cellular enzymes and energy transfer systems
• “Free Energy.” The amount of energy liberated by complete oxidation
of a food = free energy of oxidation of the food (ΔG). Free energy is
usually expressed in terms of calories per mole of substance. For
instance, the amount of free energy liberated by complete oxidation
of 1 mole (180 grams) of glucose is 686,000 calories.
Adenosine Triphosphate Is the “Energy
Currency” of the Body
• Adenosine triphosphate (ATP) is an essential link between energy-
utilizing and energy-producing functions of the body
• (1) active transport of molecules across cell membranes; (2)
contraction of muscles and performance of mechanical work;
(3) various synthetic reactions that create hormones, cell
membranes, and many other essential molecules of the body;
(4) conduction of nerve impulses; (5) cell division and
growth; and (6) many other physiological functions that are
necessary to maintain and propagate life.
• ATP is present everywhere in the cytoplasm and nucleoplasm of all
cells, and essentially all the physiological mechanisms that require
energy for operation obtain it directly from ATP (or another similar
high-energy compound,guanosine triphosphate).
• In turn, the food in the cells is gradually oxidized, and the released
energy is used to form new ATP, thus always maintaining a supply of
this substance. All these energy transfers take place by means of
coupled reactions.
Central Role of Glucose in
Carbohydrate Metabolism
• After absorption from the intestinal tract, much of the fructose and
almost all the galactose are rapidly converted into glucose in the
liver. Therefore, little fructose and galactose are present in the
circulating blood. Glucose thus becomes the final common pathway
for the transport of almost all carbohydrates to the tissue cells.
 METABOLISME KARBOHIDRAT
• DIET BERVARIASI P.U. KARBOHIDRAT >
• FUNGSI KARBOHIDRAT TERUTAMA SEBAGAI SUMBER ENERGI ( DR.
GLUKOSA )
• MONOSAKARIDA ( HEKSOSA ) HASIL PENCERNA-
AN KARBOHIDRAT TERUTAMA :
* GLUKOSA
* FRUKTOSA
* GALAKTOSA
• FRUKTOSA DAN GALAKTOSA DI HATI GLU-KOSA
Kenapa metabolisme KH penting?
• Glukosa adalah sumber energi utama
• Kadar Glukosa darah harus seimbang antara 80-
180g/dl
• bila berlebih atau berkurang dari kadar normal 
gangguan kesehatan
• Berlebih  hiperglikemia Glukosa sangat reaktif 
merusak
• Kekurangan  hipoglikemia low batt
 GLIKOLISIS
• Disebut juga EMBDEN MEYER HOFF PATHWAY
• Terjadi di dalam sitosol
• Glikolisis : oksidasi glukosa energi ( ATP )

Aerob Anaerob
( asam piruvat ) ( asam laktat )
• Pada keadaan aerob :
Hasil akhirnya asam piruvat Masuk ke dalam
mitokondria Asetil KoA

Siklus Krebs ATP + CO2+ H2O

Jalur Glikolisis
 GLIKOGENESIS
• Sintesis glikogen dari glukosa
• Terjadi di dalam hati dan otot
• Reaksi 1 : Mg++
Glukosa + ATP Glukosa 6-p + ADP
Glukokinase / Heksokinase
• Reaksi 2 :
Glukosa 6-p Glukosa 1-p
Fosfoglukomutase
• Reaksi 3 :
Glukosa 1-p + UTP UDPG + Pirofosfat
UDPG Pirofosforilase
 Enzim Glikogen sintetase ( sintase )
 membentuk ikatan α-1,4 Glikosidik ( rantai lurus ) dr
glikogen
 Enzim Pencabang ( Branching Enzyme )
membentuk ikatan α-1,6 Glikosidik ( rantai cabang )
dr glikogen

Molekul glikogen seperti pohon + cabang + rantingnya

Jalur glikogenesis dan glikogenolisis
 GLIKOGENOLISIS
• Proses pemecahan glikogen
• Dalam otot :
* tujuannya untuk mendapat energi bagi otot
* hasil akhirnya : piruvat / laktat sebab gluko-
sa 6-p yg dihasilkan dr glikogenolisis masuk ke jalur
glikolisis di otot
• Dalam hati :
* tujuannya : untuk mempertahankan kadar glukosa
darah di antara dua waktu makan
* Glukosa 6-p akan diubah menjadi glukosa
Glukosa 6-p + H2O Glukosa + Pi
Glukosa 6-fosfatase
• Enzim Glukosa 6-fosfatase terdapat di : hati, ginjal dan
epitel usus ( tetapi tidak terdapat
di otot )

• Enzim Glikogen fosforilase memutus ikatan

α-1,4 glikosidik dr glikogen

• Debranching enzyme memutus ikatan

α-1,6 glikosidik
 GLUKONEOGENESIS
• Pembentukan glukosa dari bahan bukan karbohidrat
• Pada mmalia terutama terjadi di : hati dan ginjal
• Substrat :
1. Asam laktat dr. otot, eritrosit
2. Gliserol dr. hidrolisis Triasilgliserol dlm. jar.
lemak ( adiposa )
3. Asam amino glukogenik
4. Asam propionat pd ruminansia

• Glukoneogenesis penting sekali untuk penyediaan glukosa

bila karbohidrat tidak cukup dlm diet
• Jaringan perlu pasokan glukosa kontinu sebagai
sumber energi terutama sistem saraf dan eritrosit

• Enzim bantuan :
1. Piruvat karboksilase
2. Fosfoenolpiruvat karboksikinase
3. Fruktosa 1,6 bifosfatase
4. Glukosa 6-fosfatase
METABOLISME
LIPID
Integrasi Metabolisme KOH,Lipid,& Protein

20
Pendahuluan
• Lipid yg tdpt dlm makanan sebagian besar berupa lemak, shg
metabolisme yg akan dibicarakan ini adalah metabolisme lemak
• Lemak adalah bentuk simpanan energi utama dlm tubuh
• Pencernaan lemak terjadi di dlm usus halus krn pd mulut & lambung
tdk ada enzim lipase
• Lemak ditransfer ke hati
• Lemak beredar dalam darah dan ditransfer kejaringan ekstrahepatik
• Lemak digunakan sebagai energi cadangan
• Sumber lemak :
• Makanan
• Biosintesis de novo
• Simpanan tubuh  adiposit
• Masalah utama  sifatnya tidak larut dalam air.
• Lemak  diemulsi oleh garam empedu – disintesis
oleh liver & disimpan dlm empedu  mudah
dicerna & diserap
• Transportasi  membentuk kompleks dg protein
 lipoprotein
 Digesti, mobilisasi & transport lemak
• Lemak (triasil gliserol = TAG) yg msk ke tubuh akan
dicerna di dalam usus halus
• Garam2 empedu yg dikeluarkan oleh kantung empedu
(gall baldder) terlebih dahulu akan mengemulsi lemak
(yg relatif tdk larut dlm air) shg membentuk misel
• Misel akan dipecah oleh enzim lipase pankreas mjd
gliserol & asam lemak.
Pembentukan badan keton
 Selama puasa atau pada diabetes
 oksaloasetat dikonsumsi untuk menghasilkan glukosa melalui jalur
glukoneogenesis, sehingga tidak ada yang dapat digunakan untuk
kondensasi dengan asetil KoA.
 asetil KoA diubah menjadi asetoasetat dan D-3-hidroksibutirat.
Senyawa-senyawa asetoasetat, D-3-hidroksibutirat dan aseton
dinamakan badan-badan keton.
 Penderita diabetes yang tidak diobati, maka badan-badan keton
ditemukan dalam darahnya dengan kadar yang tinggi.
Reaksi pembentukan badan keton
Reaksi degradasi badan keton
• 3-hidroksibutirat dioksidasi menghasilkan asetoasetat
dan NADH (selanjutnya diproses di rantai fosforilasi
oksidatif menghasilkan energi)
• Asetoasetat diaktivasi melalui transfer KoA dari
suksinil KoA membentuk asetoasetil KoA oleh enzim
KoA transferase. Kemudian asetoasetil KoA didegradasi
oleh tiolase menghasilkan asetil KoA (siap diproses di
siklus asam sitrat untuk menghasilkan energi)
Body Temperature Regulation and
Fever
Normal body temperatures
• The temp of the deep tissues of the body – the “core”
of the body – usually remains very cconstant - ± 1 F
(±0.6 C)
• The skin temp rises and falls w the temp of the
surroundings.
• When excessive heat is produced in the body by
strenuous exercise, the temperature can rise
temporarily to as high as 101°F to 104°F. Conversely,
when the body is exposed to extreme cold, the
temperature can fall below 96°F.
BODY TEMPERATURE IS CONTROLLED BY
BALANCING HEAT PRODUCTION AND HEAT LOSS
• HEAT PRODUCTION is a principal by-product of metabolism.
The most important of these factors are :
(1) basal rate of metabolism of all the cells of the body; (2) extra rate of
metabolism caused by muscle activity, including muscle contractions
caused by shivering; (3) extra metabolism caused by the effect of
thyroxine (and, to a lesser extent, other hormones, such as growth
hormone and testosterone) on the cells; (4) extra metabolism caused
by the effect of epinephrine, norepinephrine, and sympathetic
stimulation on the cells;(5)extra metabolism caused by increased
chemical activity in the cells, especially when the cell temperature
increases; and (6) extra metabolism needed for digestion, absorption,
and storage of food (thermogenic effect of food).
• HEAT LOSS
Most of the heat produced in the body, in the deep organs,
especially : the liver, brain, and heart, and in the skeletal
muscles during exercise.
This heat is then transferred the deeper organs and tissues
→ skin, where it is lost to the air and other surroundings.
The rate at which heat is lost is determined by two factors:
(1) how rapidly heat can be conducted from where it is
produced in the body core to the skin and (2) how rapidly
heat can then be transferred from the skin → the
surroundings.
• Insulator System of the Body
The skin, the subcutaneous tissues, and especially the fat of
the subcutaneous tissues act together as a heat insulator for
the body
• Blood Flow to the Skin From the Body Core Provides Heat
Transfer
• Blood vessels are distributed profusely beneath the
skin. Especially important is a continuous venous
plexus that is supplied by inflow of blood from the
skin capillaries.
• In the most exposed areas of the body—the hands,
feet, and ears—blood is also supplied to the plexus
directly from the small arteries through highly
muscular arteriovenous anastomoses.
• Control of Heat Conduction to the Skin by the Sympathetic Nervous
System.
Heat conduction to the skin by the blood is controlled by the
degree of vasoconstriction of the arterioles and the
arteriovenous anastomoses that supply blood to the venous
plexus of the skin. This vasoconstriction is controlled almost
entirely by the sympathetic nervous system in response to
changes in body core temperature and changes in
environmental temperature.
Sweating and Its Regulation by
the Autonomic Nervous System
• Stimulation of the anterior hypothalamus-preoptic
area in the brain either electrically or by excess heat
causes sweating.
• The nerve impulses from this area that cause sweating
are transmitted in the autonomic pathways → the
spinal cord and then through sympathetic outflow →
the skin everywhere in the body.
• REGULATION OF BODY TEMPERATURE—ROLE
OF THE HYPOTHALAMUS
The temperature of the body is regulated almost
entirely by nervous feedback mechanisms, and
almost all these mechanisms operate through
temperature regulating centers located in the
hypothalamus
• The anterior hypothalamic-preoptic area : large numbers
of heat-sensitive neurons, as well as about 1/3 as many
cold-sensitive neurons. These neurons are believed to
function as temp sensors for controlling body temp. The
heat-sensitive neurons ↗ their firing rate 2- to 10-fold in
response to a 10°C ↗ in body temp. The cold-sensitive
neurons, by contrast, ↗ their firing rate when the body
temperature ↙.
• When the preoptic area is heated→ the skin all over the
body immediately breaks out in a profuse sweat, whereas
the skin blood vessels over the entire body become greatly
dilated. → the body to lose heat, → return the body
temperature toward the normal level.
DETECTION OF TEMPERATURE BY RECEPTORS IN THE
SKIN AND DEEP BODY TISSUES
• the skin is endowed with both cold and warmth receptors. The skin has far
more cold receptors than warmth receptors—in fact, 10 times as many
in many parts of the skin. → peripheral detection of temperature mainly
concerns detecting cool and cold instead of warm temperatures.
• experimental studies suggest that the transient receptor potential family of
cation channels, found in somatosensory neurons and epidermal cells→
mediate thermal sensation
• When the skin is chilled over the entire body, immediate reflex effects are
invoked and begin to ↗ the temperature of the body in several ways: (1)
by providing a strong stimulus to cause shivering, with a resultant
increase in the rate of body heat production;
• (2) by inhibiting sweating, if this is already occurring;
and (3) by promoting skin vasoconstriction to
diminish loss of body heat from the skin
• Even though many temperature sensory signals arise in
peripheral receptors, these signals contribute to body
temperature control mainly through the hypothalamus in
the posterior hypothalamus approximately at the level of
the mammillary bodies.
• The temperature sensory signals from the anterior
hypothalamic-preoptic area are also transmitted into this
posterior hypothalamic area. Here the signals from the
preoptic area and the signals from elsewhere in the
body are combined and integrated to control the heat-
producing and heat-conserving reactions of the body.
NEURONAL EFFECTOR MECHANISMS THAT
DECREASE OR INCREASE
BODY TEMPERATURE
• When the hypothalamic temperature centers detect
that the body temperature is either too ↗ or too ↙
they institute appropriate temperature-↙ing or
temperature-↗ing procedures.
Temperature-Decreasing Mechanisms
When the Body Is Too Hot
• 1. Vasodilation of skin blood vessels. In almost all areas of the body,
the skin blood vessels become intensely dilated. This dilation is
caused by inhibition of the sympathetic centers in the posterior
hypothalamus ↗ vasoconstriction. Full vasodilation can ↗ the rate
of heat transfer to the skin as much as eightfold.
• 2. Sweating. The effect of ↗ body temperature to cause sweating is
demonstrated by the blue curve in Figure 74-7, which shows a sharp
↗ in the rate of evaporative heat loss resulting from sweating when
the body core temperature rises above the critical level of 37°C
(98.6°F).
• 3. Decrease in heat production. The mechanisms that cause excess
heat production, such as shivering and chemical thermogenesis, are
strongly inhibited.
Temperature-Increasing Mechanisms
When the Body Is Too Cold

• 1. Skin vasoconstriction throughout the body

• 2. Piloerection
• 3. Increase in thermogenesis (heat production).
Hypothalamic Stimulation of Shivering
• Located in the dorsomedial portion of the posterior hypothalamus near
the wall of the third ventricle is an area called the primary motor center for
shivering.
• inhibited : signals from the heat center in the anterior hypothalamic-
preoptic area. excited : cold signals from the skin and spinal cord.
• this center becomes activated when the body temperature falls even a
fraction of a degree below a critical temperature level. It then transmits
signals → cause shivering through bilateral tracts down the brain stem→
the lateral columns of the spinal cord, and → to the anterior motor
neurons.→↗ the tone of the skeletal muscles throughout the body by
facilitating the activity of the anterior motor neurons. When the tone ↗
above a certain critical level, shivering begins.
Increased Thyroxine Output as a Long-Term
Cause of Increased Heat Production
• Cooling the anterior hypothalamic-preoptic area ↗ production of
the neurosecretory hormone thyrotropin-releasing hormone by the
hypothalamus. This hormone is carried by way of the hypothalamic
portal veins to the anterior pituitary gland, where it stimulates
secretion of thyroid- stimulating hormone.
• Thyroid-stimulating hormone in turn stimulates ↗ output of
thyroxine by the thyroid gland. ↗ thyroxine activates uncoupling
protein → ↗ the rate of cellular metabolism throughout the body,
which is yet another mechanism of chemical thermogenesis.
Behavioral control of body temperature
• Whenever the internal body temp becomes too high, signals from
the temperature-controlling areas in the brain give → a psychic
sensation of being overheated.
• Conversely, whenever the body becomes too cold, signals from the
skin and probably also from some deep body receptors elicit the
feeling of cold discomfort.
• Therefore, the person makes appropriate environmental adjustments
to re-establish comfort, such as moving into a heated room or
wearing well-insulated clothing in freezing weather.
ABNORMALITIES OF BODY
TEMPERATURE REGULATION
• Fever
can be caused by abnormalities in
the brain or by toxic substances,
bacterial or viral infections, brain
tumors, and environmental
conditions
Resetting the temperature-regulating center
in febrile diseases – effect of pyrogens
• Many proteins,products of
proteins, and other substances,
especially lipopolysaccharide
toxins released from bacterial
cell membranes, can → the set
point of the hypothalamic
thermostat to ↗ Substances
that cause this effect are called
pyrogens.
Mechanism of Action of Pyrogens in Causing
Fever—Role of Cytokines
• When bacteria or breakdown products of bacteria are present in the
tissues or in the blood, they are phagocytized by the blood
leukocytes, by tissue macrophages, and by large granular killer
lymphocytes.
• All these cells digest the bacterial products and then release
cytokines, a diverse group of peptide-signaling molecules involved in
the innate and adaptive immune responses.
• One of the most : interleukin-1 (IL-1), also called leukocyte pyrogen
or endogenous pyrogen.
• IL-1 is released from macrophages into the body fluids and, upon
reaching the hypothalamus, almost immediately activates the
processes to produce fever, sometimes ↗ the body temperature a
noticeable amount in only 8 to 10 minutes.
• Several experiments have suggested that IL-1 causes
fever by first inducing formation of one of the
prostaglandins, mainly prostaglandin E2, or a
similar substance, which acts in the hypothalamus
to elicit the fever reaction.
• When prostaglandin formation is blocked by drugs,
the fever is either completely abrogated or at least
reduced.
Fever caused by Brain Lesions

•Another condition that frequently causes

prolonged high temperature is compression
of the hypothalamus by a brain tumor.
• Koagulopati
• Asidosis
• Hipotermi