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BIOKIMIA SISTEM

ENDOKRIN METABOLIK

Dr. Marhaen Hardjo, Ph.D, M.Biomed


Departemen Biokimia
Universitas Hasanuddin
Makassar

SKDISISTEMENDOKRIN,
METABOLIK,DANNUTRISI
Daftar Penyakit
No Kemampuan
Kelenjar Endokrin
1. Diabetes melitus tipe 1
2
Diabetes melitus tipe 2
3
Diabetes melitus tipe lain (intoleransi glukosa akibat
penyakit lain atau obat-obatan)
4
Ketoasidosis diabetikum nonketotik
5
Hiperglikemi hiperosmolar
6
Hipoglikemia ringan
7
Hipoglikemia berat
8
Diabetes insipidus
9
Akromegali, gigantisme
10 Defisiensi hormon pertumbuhan
11 Hiperparatiroid
12 Hipoparatiroid
13 Hipertiroid
14 Tirotoksikosis
15 Hipotiroid
16 Goiter
17 Tiroiditis
18 Cushing's disease
19 Krisis adrenal
20 Addison's disease
21 Pubertas prekoks
22 Hipogonadisme
23 Prolaktinemia
24 Adenoma tiroid
25 Karsinoma tiroid

Tingkat
4A
4A
3A
3B
3B
4A
3B
1
1
1
1
3A
3A
3B
2
3A
2
3B
3B
1
2
2
1
2
2

Daftar Penyakit
No Kemampuan

Tingkat

Gizi dan Metabollisme


26 Malnutrisi energi-protein
27 Defisiensi vitamin
28 Defisiensi mineral
29 Dislipidemia
30 Porfiria
31 Hiperurisemia
32 Obesitas
33 Sindrom metabolik

4A
4A
4A
4A
1
4A
4A
3B

SOAL LATIHAN 1:
Jalur yang dialami glukosa dalam metabolisme tubuh
yang benar adalah
A. Glukosa dikatabolisme melalui glikolisis menjadi 2
asam piruvat dan 2 asetil KoA
B. Glukosa disimpan sebagai glikogen melalui
glikogenolisis
C. Glukosa dikonversi menjadi asam lemak melalui
proses lipogenesis
D. Glukosa dikonversi menjadi asam amino melalui
proses sintesis protein
E. Glukosa menjalani jalur HMP-shunt yang disebut
juga jalur heksosa posfat

SOAL LATIHAN 2:
Konversi asam amino alanin menjadi piruvat
merupakan bagian dari proses ..
A. Glukoneogenesis
B. Glikogenolisis
C. Proteolisis
D. HMP-shunt
E. Biosintesis urea

SOAL LATIHAN 3:
Yang tidak sesuai dengan hormon glukagon
A. Menginaktifkan adenilat siklase
B. Counterregulatory terhadap insulin
C. Meningkatkan cAMP sebagai second
massenger
D. Merangsang proses glikogenolisis
E. Menghambat proses glikogenesis

Signaling by the
neuroendocrine system
Neuronal signals
Electrical signals
Neurotransmitters
~a micrometer
Endocrine signals
Hormones secreted into the bloodstream,
A meter or so
Both neurotransmitters and hormones interact
with specific receptors.

Two general mechanisms of


hormone action
Peptide and amine hormones
Fast
Plasma membrane receptor
Effectors: intracellular signaling
Gene expression
Steroid and thyroid hormones
Slower
Enter the cells
Nuclear receptors: transcription factor
Gene expression

Insulin
A small protein, 5.8 kDa
Important in glucose metabolism

Mature insulin
A larger precursor
preproinsulin
Remove a 23 aa signal
sequence
Formation of three
disulfide bonds
Proinsulin
Remove the C peptide
Mature insulin
A and B chains.

Proteolytic processing of the pro-opiomelanocortin (POMC)


precursor
a long polypeptide that undergoes
cleavage
a series of specific proteases
ACTH
- and -lipotropin
-, -, and -MSH
CLIP
-endorphin
Metenkephalin

Catecholamine hormones
Water soluble
Epinephrine (adrenaline)
Norepinephrine (noradrenalin)

Neurotransmitters: neurons
Hormones: adrenal glands

Eicosanoid hormones
Paracrine
Prostaglandins
Contracting smooth muscle
Pain, inflammation
Antiinfflamatory drugs

Steroid hormones
Endocrine tissues, adrenal cortex
Cytochrome P-450
Glucocorticoids
Carbohydrate
Mineralocorticoids
Electrolytes
Testosterone
Estrogen
Sexual development
Sexual behavior
Reproductive functions

The major endocrine glands


Hypothalamus
Coordination center
Regulatory hormones
Pituitary gland
via blood vessels and neurons
Posterior pituitary
Neurons from hypothalamus
Anterior pituitary
Hypothalamic hormones in blood

The major endocrine systems and their target tissues

Neuroendocrine origins of
hormone signals

Neuroendocrine origins of
hormone signals
The hypothalamus-pituitary
system.
Anterior pituitary
Releasing factors into a blood
vessel .
The anterior pituitary releases the
appropriate hormone.
Posterior pituitary
Hormones synthesized in neurons
arising in the hypothalamus.

Two hormones of the


posterior pituitary gland
Oxytocin acts on the smooth
muscle of the uterus and
mammary gland, causing uterine
contractions during labor and
promoting milk release during
lactation.
Vasopressin (also called
antidiuretic hormone) increases
water reabsorption in the kidney
and promotes the constriction of
blood vessels, thereby increasing
blood pressure.

Cascade of hormone release

In each endocrine tissue, a stimulus


from the level above is received,
amplified, and transduced into the
release of the next hormone in the
cascade.
The cascade is sensitive to regulation at
several levels through feedback
inhibition by the ultimate hormone.

Specialized metabolic functions of mammalian tissues

Metabolic pathways for


glucose 6-phosphate in
the liver
Carbohydrates, proteins, fats
Broken down
Fats in epithelial cells
triacylglycerol (TAG)
Blood capillaries to the liver
Kupffer cells: immune
Hepatocytes: transform dietary
nutrients into fuels and
precursors

Metabolism of amino
acids in the liver

Metabolism of fatty acids in


the liver
The liver is a distribution
center.

Adipocytes of white adipose tissue

Adipocytes of white and brown adipose tissue


BAT: mitochondria are prominent. Thermogenic
WAT: larger and contain a single huge lipid droplet. Store and supply
fatty acids

Distribution of brown
adipose tissue in a newborn
infant
At birth, human infants have brown
fat to protect the major blood
vessels and the internal organs.
This brown fat recedes over time,
so that an adult has no major
reserves of brown adipose.

Insulin regulation in the liver: The well-fed state


calorie-rich meal glucose, fatty acids, and
amino acids entering
liver.
Insulin - glucose uptake
by tissues.
Some glucose - exported
to brain, adipose, muscle
tissue.
In liver, excess glucose
oxidized to acetyl-CoA fatty acids TAG in
VLDLs to adipose and
muscle tissue.
verylowdensity
lipoprotein

The endocrine system of the


pancreas
Exocrine cells:
digestive enzymes in
the form of zymogens
Clusters of endocrine
cells, the islets of
Langerhans.
The islets contain , ,
and cells, each cell
type secreting a specific
peptide hormone.

Glucose regulation of insulin secretion by pancreatic cells

blood glucose level up


glucose uptake
glucose 6-phosphase
[ATP] up
closing K+ channels
Depolarizing
voltage-gated Ca2+ channels
open
Ca2+ flow
[Ca2+] up
insulin release by exocytosis

ATP-gated K+ channels in cells


(a) The octameric structure: four identical Kir6.2 subunits and four SUR1
(sulfonylurea receptor) subunits
(b) The structure of the Kir6.2 portion of the channel. Three K+ ions (green)
are shown in the region of the selectivity filter.

Sulfonyluria drugs
Type 2 diabetes mellitus
Binds to SUR1
Closing the channels, stimulating insulin release

The fasting state: the glucogenic liver

After some hours without a meal


Glucagon from pancreas
glycogen glucose
gluconeogenesis
amino acids from proteins in
muscle.
glycerol from TAGs in adipose
tissue.
fatty acids - ketone bodies other
tissues, the brain.

Fuel metabolism in the liver during prolonged fasting or in


uncontrolled diabetes mellitus
After depletion of stored
carbohydrates, proteins
become an important
source of glucose (1 to 4).
Fatty acids from adipose
tissue - ketone bodies the brain (5 to 8).

Plasma concentrations of fatty acids, glucose, and ketone


bodies during the first week of starvation
[glucose] down
[ketone bodies] up
an energy source
during a long fast.
Fatty acids cannot
serve as a fuel for the
brain; they do not
cross the blood-brain
barrier.

Diabetes
6% of the US population
Type 1 diabetes
Autoimmune destruction of pancreatic cells
Insulin deficiency
Insulin dependent
Early in life, quick and severe symptoms
Type 2 diabetes
Slow, mild, typically in older, obese individuals
Insulin is produced
Insulin-response system is broken
Insulin-resistant
Diabetes vs. obesity

Obesity and the regulation of body mass


Body mass index (BMI)
30% obese
35% overweight
Obesity vs. diabetes
Set-point model for maintaining
constant mass
adipose tissue up - leptin inhibits feeding and fat synthesis,
stimulates oxidation of fatty acids.
adipose tissue down - a lowered
leptin production - a greater food
intake and less fatty acid
oxidation.

Obesity caused by defective leptin production

ob/ob mice, no leptin


ate more food
less active, 67 g

ob/ob mice
Injected with leptin
35 g

Hypothalamic regulation of food


intake and energy expenditure

Adipose leptin
Leptin receptor
in arcuate nucleus of hypothalamus
Appetite - Fuel intake - down
Energy spending up
Heat

Sympathetic nervous system


Blood pressure, heart rate,
thermogenesis

Hormones that control eating


Leptin - adipose tissue
Insulin pancreas
Anorexigenic
neurosecretory cells - -MSH
- eat less, burn fuel
Orexigenic neurosecretory cells to inhibit the release of
NPY eat more
The gastric hormone ghrelin
-NPY release
These two opposing signals
are balanced.

The JAK-STAT mechanism of leptin signal transduction in


the hypothalamus

Leptin binding - dimerization of the


leptin receptor
JAK - Tyr phosphorylation of Rc.
STAT p-Rc dimerization
nucleus transcription - feeding
behavior and energy expenditure.

A possible mechanism for cross-talk between receptors for


insulin and leptin
Insulin receptor - Tyr
kinase
Leptin receptor Phos
by JAK
Both phosphorylate
insulin receptor
substrate-2 (IRS-2)
PI-3K - inhibition of food
intake.

Ghrelin
Ghrelin
Peptide hormone from stomach
Appetite stimulant between
meals
Injection of ghrelin intense
hunger
Insulin
Insulin levels rise immediately
after each meal, in response to
the increase in blood glucose
concentration.

SOAL LATIHAN 1:
Jalur yang dialami glukosa dalam metabolisme tubuh
yang benar adalah
A. Glukosa dikatabolisme melalui glikolisis menjadi 2
asam piruvat dan 2 asetil KoA
B. Glukosa disimpan sebagai glikogen melalui
glikogenolisis
C. Glukosa dikonversi menjadi asam lemak melalui
proses lipogenesis
D. Glukosa dikonversi menjadi asam amino melalui
proses sintesis protein
E. Glukosa menjalani jalur HMP-shunt yang disebut
juga jalur heksosa posfat

SOAL LATIHAN 2:
Konversi asam amino alanin menjadi piruvat
merupakan bagian dari proses ..
A. Glukoneogenesis
B. Glikogenolisis
C. Proteolisis
D. HMP-shunt
E. Biosintesis urea

SOAL LATIHAN 3:
Yang tidak sesuai dengan hormon glukagon
A. Menginaktifkan adenilat siklase
B. Counterregulatory terhadap insulin
C. Meningkatkan cAMP sebagai second
massenger
D. Merangsang proses glikogenolisis
E. Menghambat proses glikogenesis