Lipid Digestion and the absorption of Ca and other ions Flashcards
What are ingested lipids made up of?
Fats / Oils – triacylglycerols (TAG) – 90 % of total – typically long chain fatty acyl esters of glycerol. Fatty acids may be saturated, or unsaturated – ratio is high in animal fats, low in plant fats
Phospholipids (mostly glycerophospholipids e.g. phosphatidylcholine, or lecithin)
Cholesterol and cholesterol esters
Fatty acids
What are the two ways that ingested lipids could be?
either insoluble (e.g. cholesterol esters) or poorly soluble, in water causing special problems for digestion and absorption – only triacylglycerols and cholesterol are considered here
Lumen of the GI tract is an aqueous environment – lipids do not like aqueous environment
Describe the process of digestion?
Mouth - lingual phase – chewing
Stomach – gastric phase – contents mixed with digestive enzymes from mouth to stomach
Small intestine –
emulsification by bile synthesised by the liver
Pancreatic lipase, hydrolyses TAGs to monoglyceride and free fatty acids
Where does the first major step of fat digestion occur? What mediates it?
stomach – mediated by a lingual lipase and gastric lipase
Describe digestion of triacylgylcerols in the stomach?
Heat and movements in stomach mix food with gastric lipase which begins digestion and forms an emulsion
- Hydrolysis initially slow due to largely separate aqueous/lipid interface
- As hydrolysis proceeds, rate increases due to fatty acids produced acting as surfactants breaking down lipid globules aiding emulsification
- Emulsified fats ejected from stomach to duodenum
Gastric lipase is secreted in response to gastrin hormone (from chief cells), and is resistant to pepsin, it also has a pH of 4
Describe digestion in the duodenum?
Pancreatic lipase - main lipid digestive enzyme
Aided by bile salts from gall bladder
HCO3- in pancreatic juice neutralises stomach acid - provides suitable pH for optimal enzyme action
Pancreatic insufficiency – absence of pancreatic enzymes
The duodenum is neutral so gastric lipase is inactivated by the time it reaches the duodenum
Describe the mechanism of bile salts?
Bile salts secreted in bile from the gall bladder in response to CCK (during meals)
Once it reaches the duodenum it acts as a detergent and helps to emulsify the large lipid droplets to small droplets
Negative charges repel each other so they create a greater droplet
Describe bile salts?
amphipathic
Failure to secrete bile salts results in:
Lipid malabsorption - steatorrhoea (fat in faeces)
Secondary vitamin deficiency due to failure to absorb lipid vitamins
How to bile salts effect triclyglycerols? (TAG)
Bile salts increase surface area for attack by pancreatic lipase, but block access of the enzyme to the TAG
Problem solved by colipase, an amphipathic polypeptide secreted with lipase by the pancreas – binds to bile salts and lipase allowing access by the latter to tri- and di-acglycerides
Describe colipase?
Colipase is secreated as inactive procolipase which is activated by trypsin
Describe the digestion by Pancreatic Lipase that produces 2-Monoglyceride and Free Fatty Acids
This occurs in the duodenum – intestinal phase by pancreatic TAG lipase (main lipid digestive enzyme in adults)
Pancreatic lipase secreted from acinar cells of the pancreas in response to CCK which also stimulates bile flow
Full activity requires: colipase co-factor, Ca, alkaline pH, bile salts, fatty acids
Attacks the TAG bonds at the 1 and 3 position
Where are the final products of Lipid Digestion stored in, and released from?
Mixed Micelles
The TAGs towards the surface of the emulsion droplets are hydrolysed, they are replaced by TAGs within the core, decreasing droplet size until a mixed micelle results
Describe lipid absorption?
- PASSIVE DIFFUSION
Transfer between mixed micelles and the apical membrane of enterocytes entering by the cell by passive diffusion and membrane fatty-acid translocases, fatty acid binding protein and fatty acid transport proteins - Short chain (i.e. 6 carbon) and medium (i.e. 8-12 carbon ) fatty acids diffuse through the enterocyte, exit through the basolateral membrane and enter the villus capillaries
- Long chain fatty (i.e. 12 carbon) fatty acids and monoglycerides are resynthesized to triglycerides in the endoplasmic reticulum and are subsequently incorporated into chylomicrons
How are chylomicrons processed?
Chylomicron enters systemic circulation into the subclavian vein via the thoracic duct and distributed to tissues
Chylomicron triglyceride metabolised in capillaries (particularly muscle and adipose tissue) by lipoprotein lipase present on endothelial cells
Free fatty acids and glycerol released initially bind to albumen and are subsequently taken up by tissues
Remainder of chylomicron is a chylomicron remnant, enriched in phospholipids and cholesterol
Chylomicron remnant undergoes endocytosis by hepatocytes – cholesterol released to:
be stored
secreted unaltered in bile
oxidised to bile salts
Describe cholesterol absorption?
mainly due to transport by endocytosis in clatherin coated pits by Niemann-Pick C1-like 1 (NPC1L1) protein
- binding of cholesterol to a protein (NPC1L1) present at the plasma membrane
