Mammary Gland: the special gland
Offer no advantage to dam
Huge physiological demand from dam
Get high priority on nutrients, on expense of
dam health
Demand metabolic change
Increase metabolic rate
Increase blood flow
Increase nutrient supply
Inability to meet demand result in metabolic disorder: milk fever (hypocalcemia), ketosis (hypoglycemia)
Three major functions in milk synthesis
First, breaks down substrates to provide energy: mitochondria
Second, synthesize components of milk: lipids, casein, lactose
requires substrates, enzymes, and environment
Third, regulate non-mammary synthesized constituents: water, vitamins, and minerals
blood precursors for milk
Glucose
Acetate
β-hydroxybutyrate
triglyceride fatty acids
Amino acids
Two major sources of energy are glucose and
acetate
Energy: one of three pathways
Embden-Meyerhoff glycolytic pathway
Citric acid cycle: final common pathway of
metabolism
Pentose phosphate pathway, or shunt
Energy Production in Mammary Gland
Glucose is utilized by mammary cellsGlycolysis (Embden-Meyerhof glycolytic pathway) allows cytoplasmic anaerobic conversion of glucose to pyruvic acid and ATP, then coupled to citric acid cycle, and yield 38 ATP Utilization of pentose phosphate pathway or shunt to yield NADPH+ H+ to yield 35 ATP
In cow: of blood glucose taken up by mammary cellSixty to 70% utilized for lactose synthesis in alveolar cell Twenty to 30% oxidized via the pentose phosphate shunt for fatty acid synthesis Less than 10% utilized via glycolysis and Krebs Cycle
Milk synthesis processes
Precursors leave blood and enter extracellular fluid,
through basolateral membrane and to appropriate
synthetic pathway
Immunoglobulins transported intact through cell
Milk synthesis processes
5 routes to enter alveolar cells :
For uptake amino acids
For uptake sugars and salts
For uptake milk fat precursors
For uptake preformed proteins (immunoglobulins)
paracellular pathway
Alveolar lumen
pathway
Precursors from blood
Products form in lumen
Salts
leukocyte
Salts
leukocytes
aa
aa
glucose
Lactose glycerol
FA
FA, glycerol acetate OH-
butyrate
lipids
immunoglobulin
immunoglobulin
Tight junction
caseinFat droplet
Amino acids to proteins
Aa absorbed via basal membrane by specific aa
transport systems
Inside cell, aa covalently bound together to form
proteins at polysomes on RER
transferred from RER to Golgi apparatus to post-
translational processing and packaging as secretory
vesicle
Proteins synthesized include casein, β-lactoglobulin,
α-lactalbumin and membrane bound proteins or
enzymes
Amino acids to proteins
Secretory vesicles of milk proteins (also
lactose) move to apical membrane
secretory vesicle fuses with inner
surface of apical membrane, opening
and vesicle contents discharged into
alveolar lumen
Glucose to lactose
Glucose enters cell via basolateral membrane by specific transport mechanismSome converted to galactose, both glucose and galactose enter Golgi and forming lactoselactose drawing water into cell, Golgi, and becoming part of milkThus, Golgi apparatus involved in processing of milk proteins, synthesis of lactose, and osmotic draw for waterLactose secreted via secretory vesicles with milk proteins
Milk fat precursors to milk fat
Precursors taken up via basolateral membrane
Acetate and β-hydroxybutyrate, precursors of FA
synthesis in ruminants mammary cells
Preformed fatty acids, glycerol, and
monoacylglycerides absorbed into synthesis of
triglycerides of milk
Milk fat precursors to milk fat
Milk fat triglycerides synthesized on SER and form
small droplets
Small droplets fuse and moves toward apical
membrane and pinches off to alveolar lumen
Thus, inside cell nonmembrane-bound lipid
droplet but in alveolus lumen, milk fat globule
surrounded by membrane
Transport of Milk Components Not Synthesized in the Epithelial Cells
Immunoglobulins
Ig bind to specific receptors on basolateral
"into" cell in endocytic vesicles
transported to fuses with inner apical membrane
and releases into alveolus lumen
no serum albumin receptor, however, serum albumin may internalized along with Ig
Paracellular Pathway
way through Tight junctions between
epithelial cells
little or no "flow" of anything via Tight
junctions let except water and some ions
Tight junctions become ‘leaky’ during
mastitis or involution, or when oxytocin
causing milk ejection
Paracellular Pathway: leukocytes
leukocytes pass between epithelial cells and "break open" tight junctions
allows other extracellular components like salts to diffuse into the lumen and milk components to diffuse out of the lumen into the extracellular fluid
More in Mastitis Module
Paracellular Pathway
allow lactose and K+ move from lumen into
extracellular space, and Na+ and Cl- move opposite
Results in changing electrical conductivity of milk
(as used in detecting mastitis), increase lactose
and other milk-specific components in blood
Lactose found in urine of a cow during peripartum
period
Milk proteins found in cow's blood during
lactation and early involution
Synthetic Activity in Mammary Cells
Cells within an alveolus synchronized in
synthetic activity
some alveoli cells full of lipid droplets
and secretory vesicles, while other
none of those structures
Synthetic Activity in Mammary Cells
Secretory activity occur in two phases:
Formation of intracellular secretory structures like lipid
droplets and secretory vesicles
tall and columnar cells
Release products into lumen
Cuboidal cells , lumen fills with milk
Intracellular synthesis may decrease during this time
Synthetic activity in mammary cell
incubate mammary tissue with labeled aa,
Tracer moves through cell as a pulse
Stays in cytoplasm ~3-15 min. [newly synthesized proteins]
Appears in Golgi within 15-30 min. [newly synthesized proteins being processed]
increased in lumen 30-60 min. later [secreted proteins]
Synthetic activity in mammary cell
inject radiolabeled precursors of milk components into
animal
found in milk at varying times
Those enter by equilibrating across the apical or Golgi
membranes (Na+, K+, Cl-) take ~1 hr to reach max.
specific activity in the milk
Those enter by synthesis in the Golgi (lactose, casein,
Ca, citrate, phosphate) take 2-3 hr.
Those enter as part of milk fat synthesis take 5-7 hr.