Summary course BBS2041
Case 1: fecal characteristics teach us a lot
Structure lipids:
Lipids contain glycerol and three long chain fatty acids. The carboxyl group of the fatty acids
are ester-linked to the hydroxyl groups of glycerol, forming a triglyceride. Unsaturated fatty
acids usually have one or two double bonds. Fats are saturated and oil is unsaturated. Fats
are hydrophobic and will form an emulsion in water. Also 3 water molecules will be formed.
In cis configuration the two H atoms are on the same side of the double bond, compare to
the trans configuration in which the H atoms are on opposite sides.
Structure carbohydrates:
Carbohydrates consist of carbon, hydrogen and oxygen (CH2O)n. They are usually
monosaccharides and can be combined to form disaccharides or polysaccharides.
Digestion, transport and absorption of carbohydrates:
Monosaccharides can be absorbed directly, disaccharides and polysaccharides have to be
broken down to monosaccharides. Digestion begins in the mouth. salivary amylase present
in saliva splits starch into oligosaccharides. The carbohydrates that weren’t digested yet are
broken down by pancreatic amylase in the small intestine. Enzymes digest the
oligosaccharides to monosaccharides. Intestinal brush border enzymes, known as
dissacharids digest these products to monosaccharides. The most important brush border
enzymes are dextrinase and glucoamylase which act on oligosaccharides bigger than three
simple sugars. Maltase, sucrase and lactase act on the simple
sugars.
Glucose and galactose are shuttled by secondary active transport
with Na+ into the epithelial cells. The apical Na+-glucose SGLT
symporter and the basolateral GLUT2 transporter are used. They
then move out of these cells by facilitate diffusion and pass into the
capillaries via intercellular clefts. Fructose moves entirely by
facilitated diffusion on the GLUT5 transporter and across the
basolateral membrane by the GLUT2. The Na+-K+ pump stores
energy that drives glucose uptake by creating a steep concentration
gradient for Na+ entry into intestinal cells. As Na+ moves across the
membrane through the SGLT, it drives glucose against its gradient into the cells.
,Digestion, transport and absorption of fats:
The small intestine is the primary site of lipid digestion. Lipases remove two fatty acids from
each triglyceride. The result is one monoglyceride and two free fatty acids. Fats need bile
salts for absorption. Lipases can not penetrate these bile salts, therefore colipase is also
present to free the fats on which the lipases can work. The Sn1 and Sn3 position ester bonds
are cut forming a 2-MAG (monoacylglyceride) and 2 fatty acids.
Bile salts have a polar and nonpolar region. The nonpolar region clings to the fat molecules
and the polar region interact with water. Bile salts enter the chyme in the duodenum. The 2-
MAG, FAs and bile salts associate to form micelles, which transport them into the intestinal
mucosa. Fatty acids and monoglycerides leave the micelles and diffuse into the epithelial
cells. There they are recombined to triglycerides by the smooth ER and packaged with
cholesterol and proteins to form chylomicrons. The first step involves the synthesis of
diacylglycerol (DAG) from 2-MAG and a fatty acyl-CoA by acyl-CoA: monoacylglycerol
acyltransferase (MGAT) activity. The second, final, and committed step involves the
synthesis of TAG from DAG and a fatty acyl-CoA by diacylglycerol acyltransferase (DGAT)
activity. Chylomicrons are extruded from the epithelial cells by exocytosis. The chylomicrons
enter the lacteals and are carried away from the intestine in the lymph. The jejunum is the
primary site of absorption.
While in the bloodstream, the triglycerides of the chylomicrons are hydrolyzed to free fatty
acids and glycerol by lipoprotein lipase, an enzyme associated with capillary endothelium.
,The fatty acids and glycerol can then pass through the capillary walls to be used by tissues
for energy or stored as fats in adipose tissue. liver cells then combine the residual
chylomicron material with protein and these new lipoproteins are used to transport
cholesterol in the blood. Lipoprotein lipase is stimulated by insulin. In the chylomicron
remnant might be some triglycerides and cholesterol left. The liver takes up these remnants.
If there is too much glucose in the extra amount can be converted into fatty acids and
eventually into TAG. These are packaged in vesicles called VLDL: very low density
lipoprotein. The remnants of the chylomicron can also go into this VLDL. This VLDL has the
same fate as the chylomicrons and also travels to the capillary beds to be broken down by
the lipoprotein lipase. Chylomicrons are present after a meal. If you’re in a fasted state, there
are mainly VLDL present, because there is no energy from food.
Chylomicron à Lacteal (lymphatic vessel) à thoracic duct (vein) à arteries à capillary
beds.
When dietary TAG levels are high, TAG is incorporated into CLDs and stored temporarily in
enterocytes. CLDs are cellular organelles with a neutral lipid core surrounded by a
phospholipid monolayer with associated proteins. The majority of CLDs are present in the
jejunum.
First, TAGs and CEs are synthesized by enzymes that localize to the ER membrane. These
neutral lipids are packaged onto apolipoprotein (APO) B48 with the help of microsomal
triglyceride transfer protein (MTP). APOB48 serves as a lipid acceptor and structural protein
of CMs. MTP serves as a lipid transfer protein and chaperone for maintaining APOB48
structure. The neutral lipids, TAGs and CE, are surrounded by a PL monolayer containing
free cholesterol and proteins. This initial structure is referred to as the primordial CM. The
second step in the synthesis of pre-CMs is the expansion of the CM core by TAG
Middle chain fatty acids (12-14) <14 = short chain >14 = long chain. Short chain and middle
chain do not go into chylomicrons. They diffuse into the bloodstream by binding to Albumin
and go to the liver. Where the liver will produce VLDL.
Digestion, transport and absorption of proteins:
Proteins are digested to amino acid monomers. Free amino acids, dipeptides and tripeptides
can be absorbed. Two classes of enzymes are important in digeston: Endopeptidases
(proteases) attack the peptide bonds and break the long peptide into smaller fragments.
They are secreted as inactive proenzyme and activated in the GI tract lumen. Examples are
trypsin, pepsin and chymotrypsin. Exopeptidases release single amino acids from peptides
by chopping them off the ends, one at a time. Two forms of carboxypeptidases are important
in digestion, aminopeptidases are less important.
In the stomach pepsin cleaves bonds of tyrosine and phenylalanine. Rennin in the stomach
breaks proteins further. In the small intestine Trypsin and chymotrypsin secreted by the
, pancreas cleaves the proteins into smaller peptides. The brush border enzyme
carboxypeptidase is also activated in the small intestine.
Most of the carrier transporters for proteins are coupled to the active
transport of Na+. short chain of two or three amino acids are actively
absorbed by H+-dependent cotransport. They are digested to their
amino acids within the epithelial cells. The amino acids enter the
capillary blood by diffusion. Dipeptides and tripeptides are carried into
the mucosal cell on the oligopeptide transporter PepT1 that uses H+-
independent cotransport. Inside the epithelial cells, most oligopeptides
are digested by cytoplasmic peptidases into amino acids, which are
then transported across the basolateral membrane and into the
circulation. Some peptides larger than three amino acids are absorbed by transcytosis after
binding the membrane receptors in the luminal surface of the intestine.
Tumors mentioned in the case:
Mr A’s tumor was located at the pancreatic duct. Because if this no enzymes from the
pancreas can enter the duodenum and none of the nutrients can be digested. Mr P’s tumor
was located nearby the pancreas, probably obstructing the common bile duct. Because of
this, the bile salts can not enter the duodenum and fats can not be digested. At the Pailla of
vater the pancreatic duct and common bile duct enter the duodenum.
Fecal characteristics of malnutrition:
• Fats. You may have light-colored, foul-smelling stools that are soft and bulky. Stools
are difficult to flush and may float or stick to the sides of the toilet bowl.
• Protein. You may have dry hair, hair loss, or fluid retention. Fluid retention is also
known as edema and will manifest as swelling. Muscle atrophy
• Certain sugars. You may have bloating, gas, or explosive diarrhea.
• Certain vitamins. You may have anemia, malnutrition, low blood pressure, weight
loss, or muscle wasting.
Case 1: fecal characteristics teach us a lot
Structure lipids:
Lipids contain glycerol and three long chain fatty acids. The carboxyl group of the fatty acids
are ester-linked to the hydroxyl groups of glycerol, forming a triglyceride. Unsaturated fatty
acids usually have one or two double bonds. Fats are saturated and oil is unsaturated. Fats
are hydrophobic and will form an emulsion in water. Also 3 water molecules will be formed.
In cis configuration the two H atoms are on the same side of the double bond, compare to
the trans configuration in which the H atoms are on opposite sides.
Structure carbohydrates:
Carbohydrates consist of carbon, hydrogen and oxygen (CH2O)n. They are usually
monosaccharides and can be combined to form disaccharides or polysaccharides.
Digestion, transport and absorption of carbohydrates:
Monosaccharides can be absorbed directly, disaccharides and polysaccharides have to be
broken down to monosaccharides. Digestion begins in the mouth. salivary amylase present
in saliva splits starch into oligosaccharides. The carbohydrates that weren’t digested yet are
broken down by pancreatic amylase in the small intestine. Enzymes digest the
oligosaccharides to monosaccharides. Intestinal brush border enzymes, known as
dissacharids digest these products to monosaccharides. The most important brush border
enzymes are dextrinase and glucoamylase which act on oligosaccharides bigger than three
simple sugars. Maltase, sucrase and lactase act on the simple
sugars.
Glucose and galactose are shuttled by secondary active transport
with Na+ into the epithelial cells. The apical Na+-glucose SGLT
symporter and the basolateral GLUT2 transporter are used. They
then move out of these cells by facilitate diffusion and pass into the
capillaries via intercellular clefts. Fructose moves entirely by
facilitated diffusion on the GLUT5 transporter and across the
basolateral membrane by the GLUT2. The Na+-K+ pump stores
energy that drives glucose uptake by creating a steep concentration
gradient for Na+ entry into intestinal cells. As Na+ moves across the
membrane through the SGLT, it drives glucose against its gradient into the cells.
,Digestion, transport and absorption of fats:
The small intestine is the primary site of lipid digestion. Lipases remove two fatty acids from
each triglyceride. The result is one monoglyceride and two free fatty acids. Fats need bile
salts for absorption. Lipases can not penetrate these bile salts, therefore colipase is also
present to free the fats on which the lipases can work. The Sn1 and Sn3 position ester bonds
are cut forming a 2-MAG (monoacylglyceride) and 2 fatty acids.
Bile salts have a polar and nonpolar region. The nonpolar region clings to the fat molecules
and the polar region interact with water. Bile salts enter the chyme in the duodenum. The 2-
MAG, FAs and bile salts associate to form micelles, which transport them into the intestinal
mucosa. Fatty acids and monoglycerides leave the micelles and diffuse into the epithelial
cells. There they are recombined to triglycerides by the smooth ER and packaged with
cholesterol and proteins to form chylomicrons. The first step involves the synthesis of
diacylglycerol (DAG) from 2-MAG and a fatty acyl-CoA by acyl-CoA: monoacylglycerol
acyltransferase (MGAT) activity. The second, final, and committed step involves the
synthesis of TAG from DAG and a fatty acyl-CoA by diacylglycerol acyltransferase (DGAT)
activity. Chylomicrons are extruded from the epithelial cells by exocytosis. The chylomicrons
enter the lacteals and are carried away from the intestine in the lymph. The jejunum is the
primary site of absorption.
While in the bloodstream, the triglycerides of the chylomicrons are hydrolyzed to free fatty
acids and glycerol by lipoprotein lipase, an enzyme associated with capillary endothelium.
,The fatty acids and glycerol can then pass through the capillary walls to be used by tissues
for energy or stored as fats in adipose tissue. liver cells then combine the residual
chylomicron material with protein and these new lipoproteins are used to transport
cholesterol in the blood. Lipoprotein lipase is stimulated by insulin. In the chylomicron
remnant might be some triglycerides and cholesterol left. The liver takes up these remnants.
If there is too much glucose in the extra amount can be converted into fatty acids and
eventually into TAG. These are packaged in vesicles called VLDL: very low density
lipoprotein. The remnants of the chylomicron can also go into this VLDL. This VLDL has the
same fate as the chylomicrons and also travels to the capillary beds to be broken down by
the lipoprotein lipase. Chylomicrons are present after a meal. If you’re in a fasted state, there
are mainly VLDL present, because there is no energy from food.
Chylomicron à Lacteal (lymphatic vessel) à thoracic duct (vein) à arteries à capillary
beds.
When dietary TAG levels are high, TAG is incorporated into CLDs and stored temporarily in
enterocytes. CLDs are cellular organelles with a neutral lipid core surrounded by a
phospholipid monolayer with associated proteins. The majority of CLDs are present in the
jejunum.
First, TAGs and CEs are synthesized by enzymes that localize to the ER membrane. These
neutral lipids are packaged onto apolipoprotein (APO) B48 with the help of microsomal
triglyceride transfer protein (MTP). APOB48 serves as a lipid acceptor and structural protein
of CMs. MTP serves as a lipid transfer protein and chaperone for maintaining APOB48
structure. The neutral lipids, TAGs and CE, are surrounded by a PL monolayer containing
free cholesterol and proteins. This initial structure is referred to as the primordial CM. The
second step in the synthesis of pre-CMs is the expansion of the CM core by TAG
Middle chain fatty acids (12-14) <14 = short chain >14 = long chain. Short chain and middle
chain do not go into chylomicrons. They diffuse into the bloodstream by binding to Albumin
and go to the liver. Where the liver will produce VLDL.
Digestion, transport and absorption of proteins:
Proteins are digested to amino acid monomers. Free amino acids, dipeptides and tripeptides
can be absorbed. Two classes of enzymes are important in digeston: Endopeptidases
(proteases) attack the peptide bonds and break the long peptide into smaller fragments.
They are secreted as inactive proenzyme and activated in the GI tract lumen. Examples are
trypsin, pepsin and chymotrypsin. Exopeptidases release single amino acids from peptides
by chopping them off the ends, one at a time. Two forms of carboxypeptidases are important
in digestion, aminopeptidases are less important.
In the stomach pepsin cleaves bonds of tyrosine and phenylalanine. Rennin in the stomach
breaks proteins further. In the small intestine Trypsin and chymotrypsin secreted by the
, pancreas cleaves the proteins into smaller peptides. The brush border enzyme
carboxypeptidase is also activated in the small intestine.
Most of the carrier transporters for proteins are coupled to the active
transport of Na+. short chain of two or three amino acids are actively
absorbed by H+-dependent cotransport. They are digested to their
amino acids within the epithelial cells. The amino acids enter the
capillary blood by diffusion. Dipeptides and tripeptides are carried into
the mucosal cell on the oligopeptide transporter PepT1 that uses H+-
independent cotransport. Inside the epithelial cells, most oligopeptides
are digested by cytoplasmic peptidases into amino acids, which are
then transported across the basolateral membrane and into the
circulation. Some peptides larger than three amino acids are absorbed by transcytosis after
binding the membrane receptors in the luminal surface of the intestine.
Tumors mentioned in the case:
Mr A’s tumor was located at the pancreatic duct. Because if this no enzymes from the
pancreas can enter the duodenum and none of the nutrients can be digested. Mr P’s tumor
was located nearby the pancreas, probably obstructing the common bile duct. Because of
this, the bile salts can not enter the duodenum and fats can not be digested. At the Pailla of
vater the pancreatic duct and common bile duct enter the duodenum.
Fecal characteristics of malnutrition:
• Fats. You may have light-colored, foul-smelling stools that are soft and bulky. Stools
are difficult to flush and may float or stick to the sides of the toilet bowl.
• Protein. You may have dry hair, hair loss, or fluid retention. Fluid retention is also
known as edema and will manifest as swelling. Muscle atrophy
• Certain sugars. You may have bloating, gas, or explosive diarrhea.
• Certain vitamins. You may have anemia, malnutrition, low blood pressure, weight
loss, or muscle wasting.
