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Nutrient absorption
Owen McGuinness
Adapted from Patrick Tso and Genie Moore
Average daily intake in the U.S.
• Total energy intake: 2150 kcal– Protein: 79 g (2/3 animal, 1/3 plant sources)
– CHO: 265 g– Fat: 81 g– Alcohol: 8 g (2/3 of a beer)
From NHANES publication 245, July 2002 www.cdc.gov/nchs/data/sr_11
Intestinal Mucosa
Transport across the apical membrane
• Passive diffusion– Rate is proportional to concentration gradient– No saturation– Some lipids, water, high doses of many water soluble vitamins
• Facilitated diffusion– Rate exceeds that of passive diffusion– Saturation kinetics observed– No accumulation against a concentration gradient– Fructose, low doses of water soluble vitamins such as folate, C, B12
• Active transport – linked to Na+,K+‐ATPase– Energy requiring– Can occur against a concentration gradient– Glucose, amino acids
FAT (TG)
PROTEIN
CHO
FA, MG FA,MG,
BILE MICELLE
INTRALUMINAL INTESTINAL REMOVAL
ORAL,GASTRIC,
PANCREATIC
BILIARY SURFACE CELLULAR
FA
TG
PHASE OF DIGESTION AND ABSORPTION
CHYLO-MICRONS LY
MPH
SMALLPEPTIDES
AMINOACIDS
AAs
AAs
CA
PILL
AR
IES
OLIGO-AND DI-
SACCHARIDES
MONO-SACCHA-
RIDES
CholesterolesterLipase(nonspecific lipase)
Bile salts12 g/L
Phospholipids5 g/L
Cholesterol1 g/L
Protein2 g/L
Electrolytes9 g/L
Bilirubin0.2 g/L
Bile composition
• 98% of bile acids are conjugated with amino acids when secreted– Conjugation occurs in the liver– Glycine and taurine are the preferred amino acids in humans – Conjugation increases solubility in aqueous environment
• Cholic acid soluble to 0.28 g/l in water at 15ºC• Glycocholic acid soluble to 274 g/l
Glycocholic acid
Storage and release of bile
Bile salts
• In gallbladder, concentration is >35 mM– Spontaneously form micelles with polar portions oriented outward
• Diluted in duodenum to 10‐20 mM• Critical micellar concentration required for mixed micelle formation with products of fat digestion is approx. 2 mM
Bile salts enhance water solubility of fats derived from the diet
Bile salt conc., mM0 2 4 6 8 10 12 14 16
Solu
bilit
y, m
M
02468
101214
2-Monoglyceride
Fatty acid
DiglycerideTriglyceride
CMC
Bile acids
• Help to emulsify fats, decreasing surface area of lipid droplets
• Lower the pH optimum of pancreatic lipase from neutral to 6
• Improve transport of FA and MAG through unstirred water layer– Essential for the absorption of the fat soluble vitamins
• Release enterokinase from the brush border (? Role in trypsin activation)
• Result in some cholesterol excretion
Bile salt and colipase effects on pancreatic lipase activity
Bile salts inhibit lipase activity unless colipase is present
Time
Fatty
aci
d re
leas
ed Bilesalts
added
Colipaseadded
Diameter:TG droplet25,000 Å;Micelle 30-100 Å
Last 1/3 of the ileum:Apical bile salt transporter(active co‐transport withNa+)
Chylomicrons
• Apolipoprotein (APO‐B48)• Triglyceride• Cholesterol ester• 75 to 200 nm in diameter (VLDL 30‐80 nm)
Chylomicrons leave the enterocyte by exocytosis (reverse pinocytosis)
Medium chain triglycerides (MCT)
• Fatty acids are 6‐12 carbons long and saturated– Not common in diet, used in specialized formulas for patients with decreased pancreatic secretion or intestinal surface area
• Digestion and absorption– Hydrolyzed by lipase more rapidly than LCT – Do not require micelle formation– MCT small and soluble enough so that some appear to be absorbed intact or as diglycerides
• Enterocyte handling and transport– Little affinity for FABP– Little incorporated into chylomicrons– Transported in portal vein blood (bound to albumin)
Lymph Chylomicron Appearance(6 ml of ensure in rats)
Lipids 47:571‐80,2012
Factors affecting the efficiency of digestion and absorption
• Characteristics of the food• Nutritional status• Previous diet• Developmental changes• Genetic factors• Bowel integrity
Due to the complex nature of Lipid absorption general defects in
absorption first appear as defects in lipid absorption
Standard Fat‐Balance Method
• Requires accurate measurement of fat in diet from 2‐3 days
• Requires total stool collection for a period corresponding to the analyzed diet
• Requires analysis of the total stool by homogenization, aliquots, fat measurement
Fat Absorption by Sucrose Behenate Marker Method
Non‐absorbable Marker
The Use of a Non‐absorbable Marker Facilitates Measurement
• Animals receive diet with known concentration of marker for 4 days.
• On days 3 and 4, a fecal sample (1‐2 pellets) is taken.
• The ratio of fatty acids to behenate in the fecal sample is analyzed and absorption calculated.
O
O
ORO
RO
RO
OR
OR
OR
OR
RO
Sucrose Polybehenate, a component of olestra used in commercial preparation of snack foods is a safe, non-absorbable marker.
Fat:Marker in Diet is 3:1
Fat:Marker in Aliquot of Feces is 2:1
1/3 of Fat Absorbed
Gastroenterology 127: 139-144,2004 A novel, noninvasive method for the measurement of intestinal fat absorption Ronald J. Jandacek*, , , James E. Heubi‡ and Patrick Tso*
Sucrose behenate method was published in 2004.
The sucrose behenate method was applied in cystic fibrosis patients in collaboration with Cincinnati Children’s Hospital. J PediatrGastroenterol Nutr. 2010 April; 50(4): 441–446.
QUESTIONS?