GI Physiology of digestion and absorption 2 (Lipid, calcium, iron and vitamins) Flashcards
How much of our daily energy does ingested lipid provide?
55%
What do ingested lipids compromise 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
Are lipids soluble or insoluble in water?
Mostly are insoluble or poorly soluble in water
What enzyme hydrolyses TAGs to monoglyceride and free fatty acids in the small intestine?
PANCREATIC LIPASE
Describe the lipid digestion of TAG by lipase in the stomach?
Heat and movements in stomach mix food with gastric lipase which begins digestion and forms an emulsion….
Describe the lipid digestion of TAG by lipase 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
What does free fatty acids stimulate? (the breakdown of triglycerides and diglycerides)
CCK release from the duodenum and secretion of pancreatic lipase
What is secreted from the gall bladder in response to CCK?
Bile salts
What do bile salts do to lipids?
They act as detergents to emulsify large lipid droplets to small droplets - increasing surface area for enzymatic hydrolysis by lipase
Bile salts are amphipathic, which means?
having both hydrophilic and hydrophobic parts.
What happens if there is a failure to secrete bile salts?
Lipid malabsorption - steatorrhoea (fat in faeces)
Secondary vitamin deficiency - due to failure to absorb lipid vitamins
What do bile salts do?
What do they block?
Bile salts increase surface area for attack by pancreatic lipase, but block access of the enzyme (lipase) to the lipid with the hydrophobic core of the small droplets
How is this blockage of lipase resolved due to the bile salts?
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-glycerides
What are bile salts required for the formation of?
Mixed Micelles - a small lipid particle (4-6 nano metres) - consist of aggregates of up to 20 lipid molecules, bile salts are required for the formation of these micelles
What can these mixed micelles do?
They can sequester other fat soluble substances - include longer chain fatty acids, cholesterol, fat soluble vitamins, and phospholipids
What is TAG?
Triacylglycerols
In the duodenum what is the main lipid digestive enzyme?
Pancreatic lipase
What does HCO3- in pancreatic juice neutralise ?
Stomach acid - which provides suitable pH for optimal enzyme action
What does digestion of triglyceride by pancreatic lipase produce?
2-monoglyceride and 2 free fatty acids
How do free fatty acids and monoglycerides transfer between mixed micelles and the apical membrane of the enterocyte?
By passive diffusion
Describe how short chain and medium chain fatty acids diffuse through the enterocyte?
The diffuse through the enterocyte and exit through the basolateral membrane and enter the villus capillaries
Describe how long chain (more than 12 carbons) fatty acids and monoglycerides go through the enterocytes?
They are resynthesises to triglycerides in the endoplasmic reticulum
What happens to long chain (more than 12 carbon) fatty acids and monoglycerides?
They are taken into the enterocyte and resynthesized to triglycerides in the Endoplasmic Reticulum and are incoporated into chlylomicrons
What happens to the chlyomicron once made in the enterocyte?
It is exocytosed into the central lateral, and then carried in lymph vessels to systemic circulation via the thoracic duct
What protein is responsible for the transport of cholesterol (and thus absorption)?
NPC1L1 protein
Niemann-Pick C1-like 1 (NPC1L1) protein
What is Ezetimibe and what does it do?
binds to NPC1L1, prevents internalization, and thus cholesterol absorption.
Used in conjunction with statins in hypercholesterolaemia
What id Ezetimibe used in?
Hypercholesteroleamia
How does absorption of Ca occur?
Occurs by passive and active transport mechanisms
What is active calcium absorption regulated by? meh
1,25-dihydroxyvitamin D3 (calcitriol) and parathyroid hormone
Is calcium absorption a regulated or unregulated process?
Regulated
What is iron an important constituent of?
Haemoglobin, myoglobin and many haem-containing enzyme
What does a deficiency of iron lead to?
anaemia
What does an excess of iron lead to?
Toxic
What type of iron is absorbable?
Ferrous (Fe2) NOT ferric (Fe3)
What is the storage form of iron?
Ferratin
What happens to iron in the stomach?
It is made into Fe2 from Fe3
What is the major control on iron absorption?
Ferroportin (SLC40A1) - negatively regulated by the hormone hepcidin released from the liver when body levels are high
What is hepcidin?
A hormone released from the liver when the body iron levels are high, it negatively regulates ferroportin
Why is the absorption of vitamin B12 is a special case that requires a complex series of events
you need 6 ug per day and only get minute amounts in the diet
What is vitamin B 12 - intrisic factor complex absorbed by?
The terminal ileum by endocytosis
What are the fat soluble vitamins?
A, D, E and K
What does the absorption of fat soluble vitamins require?
Adequate bile secrete and an intact intestinal mucosa
They are incorporated into mixed micelles and chylomicrons
What are the water soluble vitamins?
B (NOT B12) C and H
Describe the transport process for water soluble vitamins?
Na dependent or independent (similar to transport of monosaccharides, amino acids and di and try peptides)
How are fat soluble vitamins absorbed?
Usually passively transported into enterocytes
What happens in the small intestine in terms of digestion of lipids?
emulsification by bile synthesised by the liver
Pancreatic lipase, hydrolyses TAGs to monoglyceride and free fatty acids
What is secreted with lipase by the pancreas?
Colipase
what happens to the chylomicron triglyceride once it has been distributed to the 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
What happens to the remainder of chylomicron? (the chylomicron remnant?)
It is enriched with phospholipids and cholesterol.
It undergoes endocytosis by hepatocytes and the cholesterol released can be stored, secured unaltered in bile or oxidised to bile salts.
