Interaksi

Metabolisme

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 Bahan bakar biologi

Setiap jaringan/organ harus memiliki sumber bahan bakar biologi yang bisa
digunakan untuk proses metabolisme. Rata-rata berat manusia membutuhkan
kalori sejumlah 1500-6000 kkal/hari atau 6000-25.000 kJ/hari
Sumber bahan bakar yang disimpan tubuh sebagai cadangan adalah:
 Triasilgliserol, disimpan di jaringan adiposa
 Protein, disimpan dalam otot gerak
 Glikogen, disimpan dalam liver dan otot gerak
Jenis bahan bakar yang terdapat pada setiap organ bergantung pada proses
metabolisme apa saja yang berlangsung.
Proses metabolisme:
 glikogenesis, glikogenolisis, glukoneognesis, glikolisis
 sintesis asam lemak, lipogenesis, lipolisis, oksidasi asam lemak, ketogenesis
 siklus TCA
 oksidasi asam amino, sistesis protein, proteolisis, siklus urea
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 Distribusi Bahan Bakar Biologi
Antar Organ

Bahan bakar biologi

Jaringan
Disimpan Dipakai Dikirim
glukosa dan keton bodi
Otak tidak ada tidak ada
saat puasa
Otot (saat
glikogen asam Lemak tidak ada
istirahat)
Otot (saat
tidak ada glukosa laktat, alanin
bekerja)

Jantung tidak ada asam lemak tidak ada

Jaringan triasilgliserol
asam lemak asam lemak, gliserol
adiposa
glikogen, asam amino, glukosa dan asam lemak, glukosa, keton
Liver
triasilgliserol asam lemak bodi

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 Interaksi
Metabolisme
antar Organ

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 Metabolisme otak
Otak harus menghasilkan ATP dalam jumlah besar untuk menjaga potensial
membran melakukan transmisi sistem syaraf
Pada kondisi normal otak hanya menggunakan glukosa untuk kebutuhan
energinya, jumlah glukosa yang digunakan sekitar 60% dari jumlah glukosa
manusia.
Otak memerlukan 120 gram glukosa per hari, setara dengan 1760 kJ atau
sekitar 15% dari total energi yang dikonsumsi perhari.
Otak merupakan organ yang bersifat anaerobik, sehingga menghabiskan 20
% total oksigen yang dikonsumsi manusia.
Otok tidak memiliki sumber bahan bakar sendiri, sehingga suplai oksigen dan
glukosa ke otak tidak boleh terhenti.
Saat puasa otak bisa menggunakan keton bodi sebgai pengganti glukosa.
Metabolisme yang terjadi: glikolisis dan siklus TCA

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 Metabolisme Otot
Otot dapat menggunakan beberapa jenis bahan bakar seperti glukosa, asam
lemak dan keton bodi. Kebutuhan energi otot gerak berbeda-beda
tergantung pada aktivitas otot tersebut.
Saat istirahat, sumber energi yang digunakan adalah asam lemak
Saat bekerja sumber energi yang digunakan adalah glukosa
Saat otot harus bekerja keras, sumber energi yang digunakan adalah
glikogen
Tiga per empat glikogen tubuh disimpan dalam otot, sisanya berada di liver
Sumber energi lain yang dimiliki otot adalah protein, tetapi jarang digunakan
karena membutuhkan proses metabolisme yang panjang dan berbahaya.
Keadaan ini berlaku untuk kondisi sangat kelaparan.

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 Metabolisme glukosa dalam keadaan aerobik dan anaerobik

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 Siklus Cori

Siklus Cori merupakan mekanisme yang digunakan otot saat sedang bekerja keras
untuk mencukupi kebutuhan glukosa. Otot akan menghasilkan laktate from glikolisis
saat jumlah oksigen terbatas. Lactat ditransport dari otot ke liver melalui aliran darah. Di
liver, lactat dirubah (melalui glukoneogenesis) kembali menjadi glukosa, kemudian
glukosa akan balik lagi ke otot.
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 Metabolisme Liver
Liver berfungsi sebagai glukostat: memonitor dan menjaga level glukosa
darah. Peran utama liver adalah sebagai tempat mensintesis bahan bakar
yang bisa digunakan oleh organ lain,
Kebutuhan energinya dapat digunakan berbagai sumber bahan bakar seperti
glukosa, asam lemak dan asam amino.

Sintesis yang berlangsung di Liver:

 Asam lemak
 Glukosa: dari penyimpanan glikogen dan glukoneogenesis
Kerja liver sangat dipengaruhi oleh kerja hormon insulin

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 Regulasi kadar gula darah oleh pankreas

Menstimulasi Glukosa darah

pembentukan meningkat
glikogen
Glukosa darah tinggi

Glukosa darah rendah

Menstimulasi
Glukosa darah
pemecahan menurun
glikogen

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 Metabolisme Jantung

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 Metabolisme Jaringan Adiposa

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 Metabolisme Darah

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 Pengaturan metabolisme glukosa darah

Animals must maintain blood glucose levels within rather narrow limits to ensure
proper functioning of the nervous system. The liver plays a major role in this
process.
The amounts of glucose available to the blood vary with the nutritional status.
In response to dietary glucose, homeostatic mechanisms come into play to
promote uptake of glucose into cells and its use by tissues, thereby lowering
glucose in the blood. When glucose levels fall, several hours after a meal, other
mechanisms promote both glucose release, from intracellular glycogen stores,
and gluconeogenesis, so that the normal level is maintained. Some of the
homeostatic mechanisms are regulated hormonally.
The most important hormone promoting glucose uptake and use is insulin,
whereas both glucagon and epinephrine act conversely, to increase blood glucose
levels. The major effects of these agents are summarized in Table 23.2.
Figure 23.2 illustrates the interplay between insulin and glucagon.

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 Pengaturan metabolisme glukosa
Animals must maintain blood glucose levels within rather narrow limits to ensure
proper functioning of the nervous system. The liver plays a major role in this process.
The amounts of glucose available to the blood vary with the nutritional status. In
response to dietary glucose, homeostatic mechanisms come into play to promote
uptake of glucose into cells and its use by tissues, thereby lowering glucose in the
blood. When glucose levels fall, several hours after a meal, other mechanisms
promote both glucose release, from intracellular glycogen stores, and
gluconeogenesis, so that the normal level is maintained. Some of the homeostatic
mechanisms are regulated hormonally.
The most important hormone promoting glucose uptake and use is insulin, whereas
both glucagon and epinephrine act conversely, to increase blood glucose levels.
The major effects of these agents are summarized in Table 23.2.
Figure 23.2 illustrates the interplay between insulin and glucagon.

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Respon
Organ
terhadap
kadar Gula
Darah
Major
events in
the storage,
retrieval,
and use of
fuels in the
fed and
unfed states
and in early
starvation.

Responses
to Metabolic
Stress

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Response to Starvation

A 70-kg human can store at most the equivalent of 6700 kJ of energy as glycogen. This source of blood glucose will be
exhausted just a few hours after a meal. Because it is critical for brain function that blood glucose levels be maintained near
4.4 mM, the organism adapts metabolically during starvation to increase the use of fuels other than carbohydrate.
About 565,000 kJ is stored in the body as triacylglycerol, largely in adipose tissue, and 100,000 kJ as mobilizable proteins,
largely in muscle. These stores provide sufficient energy to permit survival for up to several months, but the compounds
must be modified to be of use.
Triacylglycerol mobilization generates energy largely as acetyl-CoA, whose further oxidation in the citric acid cycle
requires oxaloacetate. Oxaloacetate and other citric acid cycle intermediates are used in other metabolic reactions and must
be replenished via anaplerotic pathways. The most important of these processes is the pyruvate carboxylase reaction, with
most of the pyruvate coming from carbohydrate catabolism. During carbohydrate limitation, citric acid cycle intermediates
can be provided from glycerol released from fat digestion, but glycerol is not produced in amounts adequate to maintain
levels of citric acid cycle intermediates. Alternatively, these intermediates can be produced from protein catabolism and
transamination. Consequently, proteolysis is accelerated during the first few days of starvation, because amino acids for
protein synthesis are not present in sufficient amounts to counterbalance protein breakdown, which continues at normal
rates. A major fate of the released amino acids is gluconeogenesis. During this time, the liver and muscle are shifting to fatty
acids as the dominant fuels for their own use.
Because fat breakdown has been activated, both acetyl-CoA and reduced electron carriers accumulate in the liver to the point
that the acetyl-CoA cannot all be oxidized (see here). Ketone bodies then begin to accumulate. Accumulation of
acetoacetate and -hydroxybutyrate favors reactions that catabolize these ketone bodies. Thus, the brain adapts to reduced
glucose levels by increasing the use of ketone bodies as alternative energy substrates. This trend continues for the duration
of starvation. The metabolic changes accompanying starvation compromise the organism's abilities to respond to further
stresses, such as extreme cold or infection. However, the adaptations do allow life to continue for many weeks without food
intake, the total period being determined largely by the size of the fat deposits.

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 Saat Lapar                                                        
 

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 Figure 23.5: The metabolic abnormalities in diabetes.

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Diabetes

In starvation, glucose utilization is abnormally low because of inadequate glucose supplies. In diabetes mellitus, glucose utilization is
similarly low, but it is low because the hormonal stimulus to glucose utilization--namely, insulin--is defective. As a result, glucose is present
in excessive amounts in the blood, but in deficient amounts in the cells of peripheral tissues. The consequences of insulin deficiency are
comparable to those of starvation in revealing important aspects of interorgan metabolic relationships.
Diabetes mellitus is not a single disease but rather a family of diseases.
Insulin-dependent diabetes often involves autoimmune destruction of the B cells of the pancreas, which can be caused by various factors,
including viral infection.
Some forms of diabetes have a genetic origin. Mutations in insulin structure can render the hormone inactive, and other mutations cause
defects in the conversion of preproinsulin or proinsulin to the active hormone. In these cases, treatment involves administration of insulin.
Some forms of the disease involve mutations in the structure of the cellular insulin receptor or in its intracellular activities that promote
glucose utilization. These latter forms of the disease are called insulin-resistant diabetes, because patients cannot respond to therapeutic
doses of insulin.
The failure of insulin to act normally in promoting glucose utilization by cells, with resultant glucose accumulation in the blood, starves the
cells of nutrients and promotes metabolic responses similar to those of fasting (Figure 23.5). Liver cells attempt to generate more glucose by
stimulating gluconeogenesis. Most of the substrates come from amino acids, which in turn come largely from degradation of muscle
proteins. Glucose cannot be reused for resynthesis of amino acids or of fatty acids, so a diabetic may lose weight even while consuming what
would normally be adequate calories in the diet.
As cells attempt to generate usable energy sources, triacylglycerol depots are mobilized in response to high glucagon levels. Fatty acid
oxidation is elevated, with concomitant generation of acetyl-CoA. Activity of the citric acid cycle may decrease, due to accumulation of
reduced electron carriers and/or Oxaloacetate limitation. In liver, both effects accelerate ketone body formation, generating increased levels
of organic acids in the blood. These acids can lower the blood pH from the normal value of 7.4 to 6.8 or lower. Decarboxylation of
acetoacetate, which is stimulated at low pH, generates acetone, which can be smelled on the breath of patients in severe uncontrolled
diabetic situations.
Excessive concentrations of glucose in body fluids generates other metabolic problems. At blood glucose levels above 10 mM, the kidney
can no longer reabsorb all of the glucose in the blood filtrate, and glucose is spilled into the urine, sometimes in amounts approaching 100
grams per day. Glucose excretion creates an osmotic load, which causes large amounts of water to be excreted as well. Under these
conditions the kidney cannot reabsorb most of this water. As a result, the earliest indications of diabetes are often frequent and excessive
urination, coupled with excessive thirst.
When diabetes strikes in childhood (the insulin-dependent form of the disease, representing about 10% of all cases), the metabolic imbalance
is usually more severe and difficult to control than in the milder and more common adult-onset form. The latter can often be controlled by
dietary restriction of carbohydrate, whereas treatment for juvenile diabetes usually involves daily self-injection of insulin.

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