Biosynthesis of Milk Components

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                                                             Milk Fat (Triglycerides)
 Biosynthesis of Milk Components
                                                      Ø Requires fatty acids & glycerol
 Biosynthesis of milk components occurs in the
           mammary epithelial cell                    Ø Two sources of fatty acids:
Ø Precursors from blood                                  1- Blood lipids (dietary lipids & adipose tissue)
Ø One liter of milk requires 500 L of blood              2- De novo synthesis (within the mammary gland)
Ø Fat biosynthesis
Ø Protein biosynthesis
Ø Lactose biosynthesis

     Sources of milk fatty acids                                  Milk Fat Biosynthesis

                  Milk fatty acids
                                                       Fatty acid               % of De novo      % from blood
                                                                                synthesis         lipids
                                                       C4-C10                    100               0
  Blood plasma lipids                De novo
        (50%)                                          C12                       80-90             10-20
                                                       C14                       30-40             60-70
                                                       C16                       20-30             70-80
                        Lipids form adipose            C18                       0                 100
                           tissue (20%)

                                                      Dietary fat (mainly polyunsaturated)
             Milk Fat Biosynthesis
                                                                          Polyunsaturated fatty

Dietary lipids                                                              acids (e.g. C18:3)
  Ø Saturated & unsaturated                                               Biohydrogenation &
  Ø Mostly long-chain fatty acids (C16-C18)                                                                   Mostly
                                                                                                           saturated FA
In the rumen
                                                                          Saturated   Partially             Small
  Ø Rumen microbes biohydrogenate unsaturated                             FA (C18:0) unsaturated            intestine
  fatty acids
  Ø Most dietary fats reaching the SI are saturated
  fatty acids

              Milk Fat Biosynthesis                                                         Milk Fat Biosynthesis
                       Fat in dairy Cow diets                                               De novo synthesis of fatty acids
 Ø Should not exceed 6% of the total diet (3-5%)
                                                                               Ø Occurs in the cytoplasm of the mammary cell
 Ø Main sources
                                                                               Ø Most of short and medium-chain fatty acids (C4-
    1- Animal fat: tallow, lard                                                C12) are synthesized de novo.
    2- Plant fat: oil & oilseeds (soybean, canola, flaxseed)
                                                                              Ø Precursors: β-hydroxy butyrate & acetate
                                                                              Ø Step-wise addition of acetate (C2) to β-hydroxy

                                                                     Fatty acid synthesis in the mammary
           Biosynthesis of Milk Lipids
                                                                           gland (de novo synthesis)
           Blood                      Triglycerides
   Acetate    β-hydroxybutyrate
                                                                     Ø Complete elongation produces C16
      Capillary wall                                                 Ø No further elongation beyond C16
                          Monoglycerides Free FA
     Basal membrane                                       Glycerol   Ø Premature termination of chain elongation will
                                                                     produce medium & short chain fatty acids
      Mammary cell
                                    Fatty Acyl CoA α-glycerol-P
Acetate    β-hydroxybutyrate

                                     Milk triglycerides

          Desaturation of stearic acid                               Major FA in milk, beef and pork fat
  Desaturase enzyme
                                                                                                     Milk fat   Beef fat   Pork fat
  Ø Active in the small intestine (SI) and the mammary                                 50
  gland                                                                                40
                                                                       % of total FA

  Ø More active in the mammary gland than in the SI                                    30

  Ø Desaturase C18:0 to C18:1                                                          20
  Ø The main objective is to maintain milk fat fluidity
                                                                                            C4-C12   C14:0      C16:0      C18:0      C18:1

             The Good and the Bad                        A summary of milk fatty acid biosynthesis

                                                         Diet                    Blood           Milk fatty acids
  Hypercholesteremic:          C12:0, C14:0, and C16:0
                                                         Carbohydrates           Acetate &        C4:0-C14:0
                                                                                 β-OH butyrate
  Neutral:                   > C12, C18:0

                                                         Fat (mainly             Fatty acids
  Hypocholesteremic:         C18:1, C18:2, C18:3
                                                         LCFA)                                    C18:0, C18:1,
                                                                                                 C18:2, C18:3
                                                                              Adipose tissue

 Summary of Milk Fat Biosynthesis                               Milk Protein Biosynthesis
Fatty acids Synthesis
   Ø Occurs in the cytoplasm                               The major milk proteins are only found in milk
   Ø Step wise addition of 2 carbons
                                                         Ø Casein proteins: α-, β-, κ- caseins
   Ø Elongation stops at C16
                                                         Ø Lactoglobulins: β-lactoglobulin (50% of whey protein)
   Ø Fatty acids of C14-C18 mostly from blood lipids
 Triglyceride synthesis                                  Ø lactalbumins: α-lactalbumin (25% of whey protein)
   Ø Occurs in the smooth ER
   Ø Fatty acids are esterified to the OH of glycerol

       Milk Protein Biosynthesis                                Milk Protein Biosynthesis

                                                         Ø Similar to any
Ø Milk protein are synthesized from amino acids in the
                                                         other protein
ribosome (rough endoplasmic reticulum)
                                                         Ø Requirements:
Ø There are 18 amino acids in milk
                                                            Ø Ribosome
Ø Milk contains more essential amino acids than any         Ø mRNA
other natural food                                          Ø tRNA
                                                            Ø ATP

       Milk Protein Biosynthesis                                   Milk Protein Biosynthesis

Ø Three steps:                                               2- Activation
1- Transcription                                             Ø Amino acids in the
Ø A messenger                                                cytoplasm activated
(mRNA) is formed                                             by ATP
from DNA
                                                             Ø Activated amino
Ø The mRNA carries                                           acids attached to
the genetic code of a                                        tRNA
specific protein
                                                             Ø tRNAs are specific
Ø The mRNA locates
it self in the ribosome                                      for each amino acid

       Milk Protein Biosynthesis                                    Milk Protein Biosynthesis

3- Translation
                                                                         Immune globulins (antibodies)
Ø Takes place in the
ribosome                                                        Ø Found in colostrum
Ø Anticodon in tRNA                                             Ø Enter the mammary cell from blood
recognizes the codon in                                         Ø Appear in colostrum unchanged
mRNA for a specific
amino acid
Ø Amino acid released
from tRNA and joins
the polypeptide chain

               Lactose Biosynthesis
                                                                          Lactose Biosynthesis

Ø Glucose is absolutely essential for lactose biosynthesis

Ø Blood glucose level in ruminants is 1/2 that in non

Ø 45-60% of blood glucose in ruminants from

            Lactose Biosynthesis                                         Lactose Biosynthesis
                                                              Two molecules of
                                                             1- One glucose to
                                                             UDP glucose to
                                                             UDP galactose
                                                             2- One glucose to the
                                                             3- Active transport
                                                             of UDP-galactose to
                                                             the Golgi

             Lactose Biosynthesis                                        Lactose Biosynthesis
4- Lactose is                                                7- Lactose biosynthesis
impermeable (i.e. can                                        is catalyzed by
not diffuse out of the
Golgi membrane                                               lactose synthetase
5- UDP is hydrolyzed                                         Two subunits:
to UMP and inorganic                                         a- Galatosyltransferase
                                                             b- α-lactalbumin
6- Lactose synthesis in
one-way reaction

                Water in milk                                          Minerals and Vitamins

 Ø Two sources                                                 Ø Mammary gland can not synthesize minerals &
    Ø Intracellular fluid of the secretory epithelial cell
                                                               Ø Milk minerals & vitamins are supplied from the
    Ø From blood to maintain osmotic equilibrium
                                                               Ø Na and K levels are fairly constant in milk
 Ø High lactose content = increase water influx = more
                                                               Ø Na, K, Cl & lactose, maintain osmotic equilibrium
                                                               Ø Inverse relationship between concentration of
            Remember milk ~ 87% water                                               Cl)
                                                               lactose and (Na, K & Cl) and between lactose and K

  Discharge of milk components into
                                                                          Secretion of Milk Fat
              the lumen

  Ø Milk components are kept separate inside the                  Lumen of alveolus
  epithelial cell                                                                                   Fat droplet
                                                            Fat droplet
  Ø Milk in not formed in the epithelial cells but in the   migrating
  lumen                                                                                                     Lysosome
  Ø Milk protein & lactose are carried to the apical                        Golgi body            Nucleus
  membrane by secretory vesicles and is discharged to
  the lumen without a cell membrane cover                                                         Mitochondria

                                                                                Blood Vessel

              Secretion of Milk Fat                                       Secretion of Milk Fat
      Lumen of alveolus                                           Lumen of
                                                                  alveolus     Cell pinches off       Fat droplet
Fat droplet                          Fat droplet
                                              Lysosome      Fat droplet                                     Lysosome
                Golgi body          Nucleus                                 Golgi body            Nucleus
                                       Mitochondria                                               Mitochondria

                             E.R.                                                        E.R.
                    Blood Vessel                                                Blood Vessel

              Secretion of Milk Fat                          Secretion of Milk Protein & Lactose
      Lumen of alveolus                   Fat droplet             Lumen of alveolus                   Fat droplet

                Vesicle                       Lysosome                      Vesicle                         Lysosome
Fat droplet                                                 Fat droplet
migrating                                                   migrating
                Golgi body          Nucleus                                 Golgi body            Nucleus
                                    Mitochondria                                                  Mitochondria

                             E.R.                                                        E.R.
                    Blood Vessel                                                Blood Vessel

   Secretion of Milk Protein & Lactose                                            Milk Vs Blood
Lumen of alveolus                              Fat droplet
                                                                     Blood and milk are isosmotic but are not in
              Protein micelles & lactose
                                                                               chemical equilibrium:
                                                                 Milk has:
                                                                 Ø 90 x as much sugar as blood
Fat droplet                                      Lysosome        Ø 13 x as much Ca as blood
                  Golgi body          Nucleus                    Ø 10 x as much inorganic P as blood
                                                                 Ø 9 x as much fat as blood
                                      Mitochondria               Ø 5 x as much K as blood
                                                                 Ø 1/2 as much protein as blood
                               E.R.                              Ø 1/7 as much Na as blood

                      Blood Vessel

                                                                                  Milk Ejection
                                                                 Definition: The transfer of milk from the lobulo-alveolar
                                                                    spaces into the ducts as a result of the contraction of
                                                                    the myoepithelial cell surrounding each alveolus
                  Milk Ejection
                                                                 Ø    Milk ejection is a two-component neuro-hormonal
                                                                      Ø Neural (Afferent) component
                                                                      Ø Hormonal (Efferent) component

                The Nervous System                                      The Nervous System of the
                                                                            Mammary Gland
                          System (NS)                             * Innervation of the udder is sparse
                                                                  * No direct innervation of the secretory cell
     Autonomic NS                              Somatic NS         * No parasympathetic innervation
  (involuntary control)                    (voluntary control)
                                                                  * Sympathetic innervation is associated with arteries
                                                                  * Neural receptors (somatic NS) are present in the
                                                                  skins of the teats and udder (greatest innervation is in
                    Parasympathetic                               the teat)
    NS                    NS

  Afferent (neural) component                        Efferent (hormonal) component

Ø Start with stimulation of the teat                Ø Start with the release of oxytocin into the blood
Ø Activation of nerve receptors                     Ø Oxytocin travels to the epithelial secretory cell
Ø Nerve impulses from the receptors to the brain    and binds to protein receptor on the myoepithelial
via the spinothalamic nerve tract.                  cell.

Ø Release of oxytocin from brain to the Posterior   Ø Myoepithelial cell contracts in response to
pituitary gland                                     oyxtocin.
                                                    Ø Milk expelled from epithelial cell & lumen into
                The End of the Afferent             the ductule.

                                                      Effect of premilking stimulus of
                                                        blood plasma oxytocin level
                                                                                     Premilking stimulus    No stimulus

                                                    micro units/ml






                                                                                                Minutes after teat cup

 Afferent (neural) component                                         Afferent (neural) component

                          nerves                                                                   nerves

P.P.                                                        P.P.


 Afferent (neural) component         Afferent (neural) component


 P.P.                                P.P.

                                     Oxytocin to

Efferent (hormonal) component       Efferent (hormonal) component

                  Abdominal aorta
Oxytocin                            Oxytocin
 Jugular vein   heart

Efferent (hormonal) component       Efferent (hormonal) component

Oxytocin                            Oxytocin

 Efferent (hormonal) component                  Efferent (hormonal) component

Efferent (hormonal) component                   Efferent (hormonal) component

       Contraction of an alveolus                  Contraction of an alveolus



             Oxytocin     Myoepithelial cell                     Myoepithelial cell contracts

Contraction of an alveolus              Contraction of an alveolus

                   Myoepithelial cell                        Myoepithelial Cell
     Oxytocin      contracts                                 contracts

Contraction of an alveolus              Contraction of an Alveolus

                   Releases milk into
                      duct system

                                                        Myoepithelial cell relaxes

Contraction of an alveolus               Relaxation of an alveolus

       Relaxation of an Alveolus                              Inhibition of milk ejection
                                                           Any factor that reduces the amount of oxytocin reaching
                                                           the myoepithelial cell, will inhibit milk ejection

                                                           Two inhibition mechanisms:
                                                           Peripheral inhibition: Caused by low levels of oxytocin
                                                           reaching the moyepithelial cell
                                                           Central inhibition: Caused by low levels of oxytocin
                                                           secreted by the pituitary gland

                                                                     Only central inhibition can be alleviated
                                                                             by exogenous oxytocin

   Inhibition of milk ejection
   Pain, fear,                                Postpartum
   heat stress              Pituitary            stress
                  Normal level          Low level of
Activation of     of oxytocin
sympathetic                             oxytocin
nervous system

Release of     Low level of oxytocin
catecholamines        Myoepithelial
(epinephirin &               cell

  Some facts about Oxytocin

 Ø Oxytocin can be released without mechanical
 stimulation of the udder. Visual or auditory signals
 can result in milk letdown
 Ø Oxytocin concentrations peak with 1-2 min
 following stimulation
 Ø Oxytocin has short half-life in blood (0.6-3.6 min)
 Ø Sensitivity of the neurohormonal reflex declines as
 lactation progresses.
 Ø Amount of oxytocin released declines as lactation


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