Lipid Digestion and The Exocrine Pancreas Flashcards
How much of the daily energy requirement do lipids provide?
55%
What do lipids comprise of?
- fats/oils (triglycerides)
- phospholipids
- cholesterol and cholesterol esters
- fatty acids
what are saturated fatty acid chains?
chains consisting of only single bonds so are fully saturated with hydrogen
what are unsaturated fatty acid chains?
chains consisting of one or more double bonds
what are polyunsaturated lipids?
fats containing 2 or more double bonds
are lipids soluble in water and what does this mean for digestion and absorption?
they’re insoluble/poorly soluble in water and this causes issues for digestion and absorption.
What is ‘lingual phase’?
the digestion of lipids in the mouth.
what is the gastric phase?
the digestion of lipids in the stomach.
what happens during lipid digestion in the gastric phase?
- heat and movement mix food with gastric lipase. This begins digestion and emulsification of lipids
- acid pH of gastric environment isn’t helpful for lipid digestion
- hydrolysis initially slow due to largely separate aqueous/lipid interface, rate increasing due to fatty acids produced acting as surfactants.
- emulsified lipids ejected from stomach to duodenum
What happens when the contents from the stomach (chyme) enter the SI?
they stimulate secretin and cholecystokinin secretion.
what does cholecystokinin do?
causes gall bladder contraction and bile release into duodenum and reduces GI motility
what does secretin do?
causes exocrine pancreatic juice secretion e.g.:
- bicarbonate (to neutralise chyme)
- lipases i.e. (pancreatic lipase, choesterol esterase, phospholipases).
What is used to transfer pancreatic juice and bile into the duodenum?
the pancreatic duct at the ampulla of Vater.
How are lipids digested in the SI?
- emulsified into miscelles by hepatic synthesised bile (containing bile salts and Phosphotidylcholine).
- also, pancreatic lipase is aided by bile salts, from the gall bladder, to breakdown lipids from triglycerides to monoglycerides and free fatty acids.
- HCO3- from the pancreatic juice neutralises gastric pH for optimum enzyme activity.
how does pancreatic lipase hydrolyse triglycerides?
it hydrolyses the fatty acids (FA) at the 1 and 3 positions on the triglycerides.
this produces 2-monoacylglycerol and 2 fatty acids.
how does phospholipase A2 breakdown phospholipids?
-it catalyses the hydrolysis of FA at 2-position of glycerophospholipids.
-produces lysophospholipids
(acts as a detergent as aids emulsification and digestion of lipids)
What is the role of bile salts in lipid digestion?
behaves like a detergent by breaking down large lipid droplets into smaller ones, and preventing re-clumping. This increases the surface area for lipase to work on.
what can happen if there are no bile salts secreted into the SI?
- lipid malabsorption-steatorrhoea (fat in faeces)
- secondary vitamin deficiency due to failure to absorb lipid soluble vitamins.
What does it mean by saying bile is amphipathic?
- it has a hydrophilic end, which binds to the surface of the droplet, and
- a hydrophobic end, which adsorbs onto the droplet
The access of lipase to the lipids in the small lipid droplet is blocked by the hydrophobic core of the droplet. How do we overcome this?
- the inactive form of colipase is secreted alongside lipase by the pancreas.
- It is then activated by trypsin in the duodenum and binds to bile salts and lipase allowing lipase to access the tri and diglycerides.
what are the primary products of dietary lipid digestion?
- fatty acids
- cholesterol
- monoglycerides
- lysophospholipids
what are mixed micelles?
- a mixture of all the primary products of lipid digestion with bile salts.
- mixed micelles are smaller than emulsion globules.
where are fat soluble vitamins absorbed from?
they are are packaged and absorbed from mixed micelles
what vitamins are fat soluble?
Vitamins A, D, E, K
where are mixed micelles trapped?
in the brush border of the intestinal mucosa
what process is used to absorb lipid components into the jejunum and ileum mucosa?
passive diffusion
what lipid components are absorbed into the jejunum and ileum mucosa?
- fatty acids
- monoglycerides
- lysophospholipids
- cholesterol
how are short (<6C) and medium (8-12C) chain triglycerides absorbed and hydrolysed?
using the intestinal lipases
why do short and medium chain fatty acids not require bile salts for absorption?
as they don’t need packaging co they enter the portal blood rather than lymph . Then it’s transferred to liver bound to albumin.
what makes up lipoproteins?
triglycerides, cholesterol, phospholipids,
proteins
what is a chylomicron?
a microscopic globule of lipoprotein found in blood and lymph.
where are lipids/chylomicrons excreted into?
excreted into lacteals (the lymphatic vessel of the small intestines).
how do lipids circulate into the blood from lacteals?
from lacteals, they enter the thoracic duct and enter the left subclavian vein, joining the circulatory system.
when in the circulatory system, what happens to the lipids?
they bind to receptor proteins in the membrane of endothelial cells in capillaries - mainly muscle and adipose tissue.
what is used to hydrolyse triglycerides held within chylomicrons?
lipoprotein lipase (LPL).
what happens with free fatty acids in the circulatory system?
they bind to albumin and circulate in plasma to be used by other tissues
What happens once chylomicrons have been processed by LPLs?
the remnant particle, which is a TG-depleted chylomicron, is transported to the liver for further processing.
(TG=Triglyceride)
What is found in the core of a lipoprotein?
cholesteryl esters and triglycerides
is the core of a lipoprotein polar/non-polar, and hydrophobic/hydrophilic?
non-polar and hydrophobic
what does the outer layer of a lipoprotein contain?
free cholesterol, phospholipids, specific apolipoproteins
is the outer layer of a lipoprotein polar or non-polar?
polar
what is the benefit of having a polar out layer on the lipoprotein?
it permits the lipoprotein particles to be transported in the circulation
what are apolipoproteins?
proteins that coat lipoproteins in the circulation
what is the function of apolipoproteins?
they help in the recognition of lipoproteins by enzymes that process or remove lipids from particles.
what are the classes of lipoproteins?
- Chylomicrons
- Very Low Density Lipoproteins (VLDL)
- Intermediate Density Lipoproteins (IDL)
- Low Density Lipoproteins (LDL)
- High Density Lipoproteins (HDL)
What class of lipoproteins are the largest?
chylomicrons and VLDLs as they have more triglycerides in their core
Which class of lipoproteins have the greatest density?
LDLs and HDLs as they have more cholesteryl esters in their core
Which class of lipoproteins has more proteins?
HDL
How are chylomicrons formed?
- fatty acids and monoglycerides join to make triglycerides
- triglycerides are turned into phospholipids by joining with cholesteryl esters in the endoplasmic reticulum
- phospholipids are then released as nascent chylomicrons from the ER.
- these combine with apolipoproteins to form chylomicrons
- these leave the cell by exocytosis and enter the central lacteal
- then they’re carried in lymph vessels to the systemic circulation via the thoracic duct
How are chylomicrons processed?
- enters systemic circulation into subclavian
vein via thoracic duct & distributed to tissues - Chylomicron triglycerides metabolised in capillaries by lipoprotein lipase present on endothelial cells.
- Free FA and glycerol released then bind to albumin and subsequently taken up by tissues
- Chylomicron remnant undergoes endocytosis by
hepatocytes releasing cholesterol and phospholipids.
What tissue capillaries are chylomicrons most commonly metabolised in?
muscle and adipose
what are chylomicron remnants rich in?
phospholipids and cholesterol
what are 4 products of the breakdown of chylomicrons?
- fatty acids (FA)
- glycerol
- cholesterol
- phospholipids
when endocytosis of chylomicron remnants takes place, what happens to the cholesterol released?
- some are stored
- some are secreted into bile unaltered
- some are oxidised to bile salts
what happens to VLDLs as they are transported around the blood?
- they pick up apolipoprotein (apo) C-II and additional apo E
- they deliver endogenously produced triglycerides to extrahepatic cells
- bind to capillary cells, losing triglycerides along the way
- become IDLs
What does IDL do?
converted to LDL by hepatic lipase or is taken up by liver via LDL receptor
How are LDLs produced?
by VLDLs losing triglycerides and converting into IDLs ad then further loss of triglycerides into finally becoming LDLs
What happens to LDLs as they’re transported around the blood?
-carry majority of the bloods cholesterol so they supply cholesterol to cells
how is LDL cleared from the blood?
-via LDL receptors in the peripheral cells or liver
What do peripheral cells use LDL cholesterol for?
cell membrane structure and production of hormones
Where are HDLs produced?
in peripheral tissues
How does HDL work?
- binds to receptors in vessel walls of extrahepatic tissue
- picks up cholesterol from there until full
- then transports the cholesterol to liver and glands (adrenals, ovaries, testes) for bile and hormone production.
What does Lecithin-cholesterol acyltransferase (LCAT) do?
It converts free cholesterol into cholesteryl esters which then moves into the centre of the HDL particle.
By what process is cholesterol absorbed?
active process
By what process are fatty acids and monoglycerides absorbed?
passive process
Explain the process of cholesterol absorption.
transport of cholesterol by endocytosis in clatherin coated pits by Niemann-Pick C1-like 1 proteins (NPC1L1)
How can we prevent cholesterol absorption and what condition is this used to treat?
by blocking NPC1L1 and this is used for hypercholesterolaemia.
which class of lipoprotein is good cholesterol and which is bad cholesterol?
HDL=good
LDL=bad
Why is LDL a bad cholesterol?
- because it is an atherogenic lipoprotein particle
- meaning high levels of LDL is associated with increased cardiovascular disease risk
- as it stores cholesterol in the blood stream.
Why is HDL a good cholesterol?
-high levels of HDL decreases the risk of coronary heart disease
-facilitates the transfer of cholesterol from atherogenic
lipoproteins and peripheral tissues to the liver
What is the role of peroxisome proliferator-activated receptors (PPARs) in lipid digestion?
- it binds to a specific sequence in the promoter region of target genes and activates transcription upon binding of ligands.
- PPAR can only bind to DNA as a heterodimer with the retinoid X receptor, RXP.
In which tissues are PPAR alpha and gamma found?
PPAR alpha - in tissues with high rates of beta-oxidation i.e. liver, kidneys, heart, muscle.
PPAR gamma - in adipose tissue and intestines
What ligands bind to PPAR alpha and gamma?
PPAR alpha - fatty acids and fibrates
PPAR gamma - arachidonic acid and glitazones
What are the mechanisms of action of PPAR alpha?
1, regulates the expression of many genes critical to lipid and lipoprotein metabolism
- increases free fatty acid uptake and catabolism
- decreases FFA and VLDL synthesis
- lowers plasma triglyceride levels and elevates HDL cholesterol levels
What are the mechanisms of action of PPAR gamma?
- hypotriglyceridemic action via indction of lipoprotein in adipose tissue
- stimulate lipid uptake and adipogenesis by adipocytes
- increase FFA synthesis and uptake by adipocytes
- lowers plasma triglyceride levels
- increases insulin sensitivity
How are fat soluble vitamins absorbed (i.e. A, D, E and K)?
- incorporated into mixed micelles, they are passively transported into enterocyes usually.
- Incorporated into chylomicrons adnd VLDLs, it’s distributed by intestinal lymphatics.
What vitamins are water soluble?
vitamin B (besides B12), cnd H.
Explain the process of vitamin B12 absorption!
- ingested in food and haptocorin secreted into salivary glands
- stomach acid releases vitamin B12 from food
- haptocorin binds bit B12 released in stomach
- stomach parietal cells release intrinsic factor
- pancreatic proteases digest haptocorin in small intestine, vit B12 released.
- vit B12 bids to intrinsic factor in SI
- vit B12-intrinsic factor complex are then absorbed in the terminal ileum by endocytosis.
