owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion –...
Transcript of owen nutrient absorption talk · Transport across the apical membrane • Passive diffusion –...
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Nutrient absorption
Owen McGuinness
Adapted from Patrick Tso and Genie Moore
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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
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Intestinal Mucosa
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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
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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
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CholesterolesterLipase(nonspecific lipase)
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Bile salts12 g/L
Phospholipids5 g/L
Cholesterol1 g/L
Protein2 g/L
Electrolytes9 g/L
Bilirubin0.2 g/L
Bile composition
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• 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
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Storage and release of bile
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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
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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
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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
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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
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Diameter:TG droplet25,000 Å;Micelle 30-100 Å
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Last 1/3 of the ileum:Apical bile salt transporter(active co‐transport withNa+)
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Chylomicrons
• Apolipoprotein (APO‐B48)• Triglyceride• Cholesterol ester• 75 to 200 nm in diameter (VLDL 30‐80 nm)
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Chylomicrons leave the enterocyte by exocytosis (reverse pinocytosis)
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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)
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Lymph Chylomicron Appearance(6 ml of ensure in rats)
Lipids 47:571‐80,2012
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Factors affecting the efficiency of digestion and absorption
• Characteristics of the food• Nutritional status• Previous diet• Developmental changes• Genetic factors• Bowel integrity
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Due to the complex nature of Lipid absorption general defects in
absorption first appear as defects in lipid absorption
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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
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Fat Absorption by Sucrose Behenate Marker Method
Non‐absorbable Marker
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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.
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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.
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Fat:Marker in Diet is 3:1
Fat:Marker in Aliquot of Feces is 2:1
1/3 of Fat Absorbed
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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.
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QUESTIONS?