BIOSINTESA AIR SUSU
1. Bahan Baku (prekusor)
Kandungan Nutrien Dalam Darah dan Susu Sapi
No
1.
2.
3.
4.
5.
Nutrien
Air
Glukosa
Lactosa
Asam amino
Casein
- Lactoglobulin
- Lactalbumin
Immunoglobulin
Serum albumin
Triasilgliserol
Fosfolipida
Asam sitrat
Ca
P
K
Na
Cl
Darah
SUSU
91
0.05
0
0.02
0
0
0
2.6
3.2
0.06
0.25
trace
0.01
0.01
86
trace
4.6
trace
2.8
0.32
0.13
0.07
0.05
3.7
0.035
0.18
0.13
0.10
0.025
0.34
0.35
0.15
0.05
0.11
Bahan Baku menurut Komponen Susu
1. Glukosa :
- Bahan baku laktosa susu
- Sumber -gliserol
- Dibutuhkan dalam perubahan NADP -> NADPH
- Sumber ATP
2. Asam amino :
- Bahan baku casein susu
- Sumber glukosa
3. As. lemak (asetat, -hidroksi butirat, NEFA) :
- Bahan baku asam lemak susu
4. Vitamin dan Mineral :
- Diabsorbsi langsung dari darah
2. Biosintesis Lemak Susu
• Terjadi di sitoplasma sel sekretori kelenjar ambing.
• Kadarnya dalam susu berfluktuasi (2,5% – 6%); sangat
dipengaruhi oleh jenis pakan, 2,5 – 6%.
• 75 – 90% lemak susu berupa trigliserida yg mengandung asam
lemak rantai pendek (C4-C14) dan rantai panjang (C > 14)
• C4 – C14 disintesis dari asetat dan β-hidroksi butirat
• C > 14 disentesis dari trigliserida plasma (NEFA) dan palmitat.
Sources of Fatty Acids
The fatty acids used to synthesize the milk triglycerides may arise
from two sources:
1) From breakdown of blood lipids From 40 to 60% of the milk fatty
acids come from the blood. These are primarily derived from very low density
lipoproteins (VLDL), which are synthesized in the intestine or liver. VLDL are
composed of 90 to 95% lipid (55-60% triglyceride) on the inner core and 5 to
10% protein at the outer urface.
2) From de novo synthesis within the mammary epithelial
cells. Synthesis of short and medium chain fatty acids in the mammary gland occurs by
de novo synthesis (synthesis from the start, or synthesis of new molecules of fatty acids
from precursors absorbed from the blood) wich occurs in the cytoplasm of the mammary
epithelial cell.
In the ruminant, the carbon sources used for FA synthesis are acetate (the most
important one) and b-hydroxybutyrate (BHBA). Glucose is a carbon source for FA
synthesis in nonruminants. The reducing equivalents needed for FA synthesis come from
NADPH2 (nicotinamide adenine dinucleotide phosphate, reduced form).
Origin of Milk Fat
Fats
NDF & NFC
Rumen
Saturation + Hydrolysis
Intestine
Saturated FA+ MG
“Glucose”
Acetate
Butyrate
VLDL
NEFA
TG
Adipose
tissues
Acetate
BOHB
TG
Acetate
BOHB
Liver
Fatty Acids
VLDL
Ketones
FA = Fatty acids
TG = Triglycerides
MG = Monoglycerides
BOHB = B-hydroxybutyrate
NEFA = Non-Esterified Fatty acids
VLDL - very low density lipo-proteins
Acetate
BOHB
l
Glycerol
Fatty acids
Milk Fats
Mammary Gland
The two key enzymes involved in FA synthesis in the MG are:
1. Acetyl-CoA Carboxylase, which is the rate limiting enzyme
for the fatty acid synthesis pathway.
2. Fatty Acid Synthetase, which is a large complex of enzyme
activities responsible for the chain elongation of the fatty acid
chains.
The relative proportions of milk fatty acids derived from de novo synthesis or
blood lipids is dependent on carbon chain length of the fatty acid. Typically,
shorter chain fatty acids arise predominantly from de novo synthesis inthe
epithelial cell, while longer chain fatty acids arise directly from blood lipids. An
example is given in the table below for the cow.
Proportional contribution of sources of fatty acids in cow milk
Fatty Acid
C4 -C10
C12
C14
C16
C18
% of FA from
De novo synthesis
100
80-90
30-40
20-30
0
% of FA from
VLDL Fatty Acid
0
10-20
60-70
70-80
100
In ruminants, fermentation of dietary carbohydrate in the
rumen results in formation of volatile fatty acids (VFA's):
especially, acetate, propionate, and butyrate.
Komposisi asam lemak dalam trigliserida air susu
Asam lemak
Jenuh :
Butirat
Kaproat
Kaprilat
Kaprat
Laurat
Miristat
Palmitat
Stearat
Tak jenuh :
Oleat
Linoleat
lainnya
Panjang C
Manusia
Babi
Kambing
Sapi
4
6
8
10
12
14
16
18
2
8
9
23
9
2
2
2
2
2
2
29
6
7
5
4
13
7
12
24
51
10
3
1
2
3
9
21
11
18: 1
18: 2
-
34
7
8
35
14
12
17
3
3
31
5
4
Fatty Acid Synthesis
Summary of Fatty Acid Synthesis Reactions:
Each cycle through the malonyl-CoA pathway results in two
carbons being added to the FA chain.
The total reaction is (given here for synthesis of palmitate; C16):
Acetyl-CoA + 7 Malonyl-CoA + 14 NADPH2
are catalyzed by Fatty Acid Synthetase to yield :
Palmitate + 7 CO2 + 14 NADP + 8 CoA
The FA Synthesis Pathway involves the following steps :
Activation - acetyl-CoA carboxylation
Elongation - the malonyl-CoA pathway
Condensation step
Reduction step
Dehydration step
another reduction step
The cycle is then repeated
Summary of FATTY ACID SYNTHESIS
• it occurs in the cytoplasm
• the intermediates are linked to ACP (acyl carrier protein)
• the enzymes of FA synthesis are linked in a complex
• elongation occurs by 2 Carbons/cycle (source of 2-Carbon units
is always acetyl-CoA at the beginning of each cycle)
• the required reducing agent is NADPH2
• in general, elongation stops at C16
These two things are required for de novo FA synthesis:
• a source of carbons, specifically acetyl-CoA
• a source of reducing equivalents, specifically NADPH2
The origin of each of these varies among species, particularly in
comparing ruminants and nonruminants.
Triglyceride Synthesis
Synthesis of triglycerides from FAs (preformed from the blood or
synthesized in the cell by de novo synthesis) occurs at the
cytoplasmic surface of the smooth endoplasmic reticulum (SER).
The FAs are esterified to the hydroxyl groups of the glycerol
molecules. This occurs by a series of esterases.
There is some specificity of which carbon on the glycerol is used to
esterify particular chain length FAs.
In the cow:
*
*
*
*
C16 is found predominantly on the #2 carbon of glycerol,
C18 FAs mostly on the #3 carbon,
C4-C8 mostly on the #3 carbon, and
C10-C14 distributed among each of the glycerol carbons.
Lipid Droplet Formation
Inside the mammary epithelial cell, as the triglycerides are synthesized at the outer
surface of the SER (smooth endoplasmic reticulum), they start coalescing and form
micro lipid droplets.
These micro lipid droplets bud or bleb off from the SER surface into the cytoplasm.
The micro lipid droplets may be secreted from the cells directly as very small
milk fat globules (less than 0.5 mm), they may fuse with each other to form larger
droplets (cytoplasmic lipid droplets), and they may fuse with cytoplasmic
droplets, ultimately resulting in formation of larger milk lipid droplets.
Milk fat globules (in milk) range from less than 0.5 to greater than15 mm. The
micro and cytoplasmic lipid droplets are not surrounded by a lipid bilayer
membrane but apparently are surrounded by a nonbilayer coating made of
protein and polar lipid (gangliosides).
This surface coating prevents coalescence of the droplets with lipids in the cell,
yet permits fusion between droplets. In fact, the protein and ganglioside of this
coating, along with calcium, are involved in the fusion of the droplets.
Secretion of Milk Fat
As the large milk lipid droplets migrate to the apical surface of the
cell they continue to push outward and are enveloped by the apical
membrane of the cell.
This membrane eventually fuses at the base, releasing the
membrane-bound milk fat globule, and closing the cell's apical
membrane so ere is no hole in it. So, the milk fat globule is
membrane-surrounded and has a number of membrane-associated
proteins.
These proteins and others trapped during the process of
separating cream from whole milk (usually by some type of
centrifugation) are important for the whipping properties of cream.
Overview of Milk Fat Synthesis
The components of milk fat synthesis are summarized in the diagram
below.
This fat globule membrane helps to stabilize the fat globules in an
emulsion within the aqueous environment of milk (remember that
cow milk is about 87% water). Lipid has a lower density than
water, so when raw milk is centrifuged the fat rises to the top
resulting in the cream layer (see image).
Milk fat is the primary component of cream.
Below milk was centrifuged to separate the
cream and the skim milk (also called the plasma
phase of milk).
Homogenization is the process by which fat
globules in fluid milk are broken into sizes small
enough that they will not rise in the milk to
form cream under normal milk storage
conditions. This is important for processing,
storage and consumption of cow milk.
3. Biosintesis Laktosa Susu
• Berlangsung di aparatus golgi sel sekretori kelenjar ambing.
• Bahan baku sintesis laktosa adalah glukosa
• Kadarnya dalam susu dipertahankan tetap yaitu 3,6 – 5,5%
• 1 molekul laktosa tersusun dari 1 mol glukosa dan 1 mol
galaktosa yang juga berasal dari glukosa. Jadi untuk sintesis 1
mol laktosa butuh 2 mol glukosa
• 80% glukosa plasma digunakan untuk sintesis laktosa, 50-60%
diubah menjadi galaktosa dahulu.
Lactose is a disaccharide composed of D-galactose and D-glucose.
• Laktosa bertanggung jawab mempertahankan keseimbangan
tekanan osmotik antara darah dan lumen susu.
• Semakin tinggi produksi laktosa semakin banyak air yg
dialirkan ke lumen susu produksi susu meningkat.
• Ketersediaan glukosa dalam sel sekretoris kelenjar ambing
sangat penting dalam peningkatan produksi susu.
• Glukosa merupakan faktor pembatas pada sapi perah
berproduksi tinggi.
Lactose
Biosynthesis
OH
OH CH2
OH
OH
CH2
O
O
OH
OH
Galactose
Liver
Blood
Secretory Cell
Propionate
CH3 CH2
O
C O-
O
OH
Glucose
Golgi Apparatus
Water
LACTOSE
Glucose
Glucose
Glucose
A
Glucose-P
Glucogenic amino-acids
(glutamte, aspartate
serine, etc.)
Galactose
B
Galactose
A = galactosyl transferase; B = alpha lactalbumin
OH
Ringkasan reaksi biosentesa laktosa
ATP + glukosa
Glukosa-6P
Heksokinase
Phospoglucomutase
UTP + Glukosa-1P
Glukosa- 6P + ADP
Glukosa-1P
UDP-Glukosa + PP
UDP-Glucose
Pyriphosporylase
UDP-Glukosa
UDP-Galactose
4-epimerase
UDP-Galaktosa+Glukosa
UDP-Galaktosa
Laktosa + UDP
Lactose synthetase
Upaya meningkatkan produksi susu melalui
peningkatan sintesis laktosa
1. Pemilihan bahan pakan yang tepat
dipilih bahan pakan yang banyak memberikan pasokan
glukosa pada sel kelenjar ambing.
a. Bahan pakan yang menghasilkan propionat dalam
rumen
b. Bahan pakan kaya pati namun lolos degradasi rumen,
sehingga menghasilkan glukosa dalam usus.
2. Manipulasi Metabolisme Nutrien
• Meningkatkan uptake glukosa oleh sel kelanjer ambing
(manipulasi sistem trasport glukosa)
• Pengambilan glukosa oleh sel kelenjar ambing
membutuhkan IGF-I (pada sapi) dan hormon insulin
(selain sapi)
• Potensi aktivitas insulin dan IGF-I dapat ditingkatkan oleh
Glucoce Tolerance Factor (GTF)
• GTF adalah suatu ligan yang terdiri dari Cr3+ dan asam amino
glisin, sistein, asam glutamat dan niasin
Glucoce Tolerance Factor (GTF)
- COOH
Glisin
N
Cr3+
Glutamat
atau
Glisin
N
COOH -
Sistein
Difusi
Glukosa
Na+
Insulin
Ligan GTF
Transport Glukosa Melalui Membran Sel
4. Biosintesis Protein Susu (Casein)
• Terjadi di ribosom sekretoris kelenjar ambing, menggunakan
bahan baku asam-asam amino
• Kadarnya dipertahankan tetap yaitu 2,9 – 5%
• Kandungan asam amino esensial tertinggi dalam susu adalah
leusin, lisin dan valin; sedangkan asam amino non esensial
tertinggi adalah asam aspertat, asam glutamat dan prolin.
• Sintesis protein susu membutuhkan energi dalam bentuk ATP.
Ringkasan Tahapan Reaksi Sintesis Protein Susu
1. Asam amino + ATP
-----------> Aminoasil-AMP +Pi
2. Aminoasil-AMP + t-RNA ----------- > Aminoasil-tRNA + AMP
3. (Aminoasil-tRNA)n + GTP
---------- > AA1–AA2–AA3 +
GDP+tRNA
Kandungan AA dalam Protein air susu (g/100 g protein)
AA esensial
Sapi
Babi
AAnon esensial
Sapi
Babi
Arginin
Histidin
Isoleusin
Leusin
Lisin
Metionin
Fenilalanin
Treonin
Triptofan
Valin
3.6
2.7
5.6
9.7
7.9
2.5
5.2
4.6
1.3
6.6
5.6
2.5
5.1
8.2
6.0
1.5
4.2
4.1
1.3
5.2
Alanin
As. Aspartat
Sistin
As. Glutamat
Glisin
Prolin
Serin
Tirosin
3.6
7.2
0.7
23.0
2.0
9.2
5.8
5.1
5.1
1.6
11.2
2.0
5.8
5.5
Biosintesi Komponen Susu Di Dalam Sel Sekretoris Kelenjar Ambing
DARAH
MEMBRAN SEL
SEL KELENJAR AMBING
2-monogliserida
Triasilgliserol
(Kilomikron, LDL)
FFA
Asam lemak
Lemak
susu
-gliserol-P
Gliserol
NEFA
Asetat
Asetat
-hidroksibutirat
-hidroksibutirat
NADP +
Triose-P
PPC
Glukosa 6-P
Glukosa
NADPH
Glukosa
Glukosa -1-P-UDP
Laktosa
susu
Sitrat
-ketoglutarat
Isositrat
OP
NAD +
NADH
ADP
ATP
Pi
Asam amino
Asam amino
Mineral
(Ca+, P+, Cl-, K+,
Mg+, Na+)
(Ca +, P+, Cl-, K+, Mg+, Na+)
*NEFA = Asam lemak tak teresterifikasi
OP = Fosforilasi oksidatif
;
Amino
Acil-AMP
PPC = Siklus pentosa fosfat ;
Protein
susu
Mineral
susu