Digestion and absorption 2 Flashcards
In what pH does lingual and gastric lipase work?
Acidic pH
What is the function of the lingual and gastric lipases?
They break TAGs to 1,2-diacylglycerides and FFAs
What secretes the gastric lipase?
The gastric chief cells in the fundal mucosa in the stomach (with an optimum pH of 4-6)
- Acidic lipase is important for neonates and patients with insufficient pancreatic function (like in cystic fibrosis)
Where are dietary fats absorbed in the body?
Small intestine
Where does the emulsification of the dietary lipid occur?
In the duodenum, which increases the surface area of the lipid droplets
How does emulsification of the dietary lipid occur?
1) Bile salts act as detergents
- Bile salts are bile acids + glycine or taurine
2) Mechanical mixing due to peristalsis forming micelles
How are bile salts formed?
- Stored in the gallbladder
- Bile acids are synthesized from cholesterol, and then they are conjugated by amino acids to form bile salts
What is a colipase?
- the pancreas secretes Colipase as a procolipase and it gets activated by trypsin
- Colipase is a crucial cofactor for pancreatic lipase which is essential for the digestion of fats
- Colipase anchors the pancreatic lipase to the surface of the lipid droplets in the small intestine
What is the function of pancreatic lipase?
- It removes fatty acids (from TAGs) at carbon 1 and 3
- It results in 2-monoacylglycerol and FFAs
(FYI: If we add 1 fatty acids with glycerol by ester bond it will be called monoacylglycerol
2 fatty acids with glycerol by ester bond it will be called diacylglycerol
3 fatty acids with glycerol by ester bond it will be called triacylglycerol
TAGs will be degraded by pancreatic lipases it will hydrolyze ester bond at carbon number 1 and 3 releasing MAG and 2 fatty acids)
What is the relationship between cystic fibrosis and pancreatic lipase?
Pancreatic lipase deficiency in cystic fibrosis results in significant malabsorption
What is orlistat?
It is an anti-obesity drug that inhibits gastric and pancreatic lipases and thus decreases fat absorption
What is a lysophospholipid?
They are proteins that aids in digestion of other lipids via breaking up fat molecules into small micelles
What is phospholipase A2?
- Secreted by the pancreas into the intestine
- It is a lysophospholipid that hydrolyzes the ester linkage between the fatty acid and the hydroxyl on carbon 2 of the phospholipid
What is the enzyme that degrades cholesteryl ester?
pancreatic cholesteryl ester hydrolase (cholesterol esterase), which produces cholesterol plus FFAs
- Bile salts increase its activity
What happens to the monoacylglycerol in the enterocytes?
They are acylated into triglycerides via the monoacylglycerol pathway
- Short and intermediate-chain fatty acids will enter directly into the enterocyte and go to the blood
- Long-chain fatty acids will get esterified with glycerol
- Glycerol will then go to the hepatic portal vein (as it is the only site that can deal with it, having the enzyme glycerol kinase)
What happens to the cholesterol inside the enterocytes?
- It is esterified into fatty acid-forming cholesteryl ester via the enzyme ACAT (Acyl CoA Cholesterol Acyl Transferase)
How are lipids absorbed by intestinal mucosal cells?
- The primary products of dietary lipid degradation with the bile salts from mixed micelles
- Short and medium chain length FAs don’t need micelles formation to be absorbed (they pass directly)
Where are TGs and cholesteryl ester resynthesized?
- Enterocytes in the intestinal mucosal cell will resynthesize TAGs, MAG, fatty acids, and cholesterol
- They will be packaged together with the proteins to form aggregates (chylomicrons)
How are triacylglycerol and cholesteryl esters by the intestinal mucosal cell
1) Long fatty acids are converted to fatty acyl CoA (via fatty acyl synthetase “thiokinase”)
2) Short and medium FA are released into the portal circulation where they are carried by serum albumin to the liver
3) 2-monoacylglycerol + 2 fatty acyl CoA are converted to triacylglycerol (via acyltransferase)
- In addition to phospholipids, cholesterol esters are synthesized by a family of acyl transferase
How are the lipids secreted from the intestinal mucosal cells?
- Newly synthesized TGs and cholesterol esters are packed as oily droplets surrounded by protein and phospholipid and unesterified cholesterol (which increases the solubility (named chylomicrons)
What is a lipoprotein?
They are lipid-binding proteins found in the blood that are responsible for transporting of cholesterol, cholesterol esters, phospholipid, and triacylglycerol between the organs
What is a apolipoprotein?
Lipoprotein without lipids
How are lipids packaged inside the enterocytes?
- Once inside the enterocyte (fatty acids and monoglycerides) are transported into the endoplasmic reticulum, where they are used to synthesize triglycerides
- In the Golgi, the triglyceride is packaged with cholesterol, and other lipids into particles (chylomicrons)
- Chylomicrons are extruded from the Golgi into exocytotic vesicles which are transported through exocytosis
- Chylomicrons are then transported to the lymphatic vessels first which penetrates into each villus
- The chylomicron-rich lymph then drains into the system lymphatic system (which will then rapidly flow into the blood)
How do FFAs transport in the body?
1) Fatty acids are kept bound with the intestinal fatty acid binding protein (I-FABP)
2) Free fatty acids transported in the blood bound to albumin
How is cholesterol absorbed?
-Niemann-Pick C1-Like 1 (NPC1L1) Is a transport protein that carries cholesterol from the intestinal lumen into the enterocyte
- Cholesterol is either esterified or remains non-esterified
What is the definition of malabsorption?
The inability of the intestine to absorb nutrients or specific nutrients
What are the causes of malabsorption?
1) Intraluminal/luminal (Pancreatic insufficiency, decreased bile acid secretion, bacterial overgrowth, lack of intrinsic factor)
2) Mucosal (like lactase or sucrase-isomaltase deficiency, hartnup disease, celiac disease, whipple disease “a result of bacterial infections”)
3) Post-absorptive (lymphatic obstruction)
4) Inflammatory conditions
5) Cystic fibrosis
6) Lactose intolerance
7) Disease of the gall bladder, liver
8) Radiation therapy
What are the symptoms of malabsorption?
1) Hypovitaminosis symptoms
2) Steatorrhea
3) Weight loss
4) Weakness
What are the tests of malabsorption?
1) Quantitative stool fat test (if more than 5g per day then it is steatorrhea)
2) D-xylose absorption test (evaluate the S.I ability to absorb simple sugars “Is it intestinal mucosal damage or pancreatic insufficiency”)
- Helps in differentiating between causes of malabsorption
- It works because D-xylose is a simple sugar that does not require enzymes for digestion rather it requires an intact mucosa only (the patient drinks water containing 25 grams of D-xylose and then urine and blood samples are collected to measure D-xylose if decreased then their is a problem in the mucosa)
3) Stool elastase activity (diagnosis of pancreatic insufficiency)
- Abnormal = pancreatic disease
- Normal = bacterial bowel overgrowth
4) Blood test to check for vitamin deficiency
- These tests are done in order if test one is normal then Khalas the patient is normal
