Flashcards in Digestion of fats Deck (86):
What type of bile acids are formed in the liver?
Primary bile acids.
What type of bile acids are formed by bacterial action in the intestine?
Secondary bile acids.
Name two primary bile acids.
Cholic acid. Chenodeoxycholic acid.
Where in the enterocyte are the products of lipase digestion built back up into TAG to for chylomicrons?
The smooth endoplasmic reticulum.
The circular muscle fibres behind the bolus of food contract to constrict the gastrointestinal tract and force the bolus of food forwards; and the longitudinal fibres in front of the bolus of food contract to shorten the gastrointestinal tract so the walls bulge out so it can receive the bolus. This wave of contraction is repeated many times.
What are the two pathways of lipid metabolism?
Exogenous (happens after a meal), and endogenous (happens all the time).
What enzyme converts chylomicrons to chylomicron remnants?
Lipoprotein lipase on the luminal surface of the endothelium.
What proportion of bile salts are excreted in the faeces, what proportion are reabsorbed?
5% excreted in faeces, 95% reabsorbed in ileum to be recycled.
What protein transports free fatty acids in the blood?
Why is cholesterol transported in lipoproteins as cholesterol ester?
Cholesterol is amphipathic, cholesterol ester is non-polar, it needs to be non-polar to be inside the phospholipid monolayer.
Name one of the biggest apoproteins, which is found on the surface of VLDLs and is very important.
What is the function of chylomicrons?
To deliver dietary lipids to adipose tissue for storage, and to the liver via chylomicron remnants.
What is the function of VLDLs?
To deliver triglycerides synthesised in hepatocytes to adipose tissue for storage, and therefore form IDLs and LDLs.
What is the function of LDLs?
To deliver cholesterol to any cells in the body that need it, including macrophages.
What is cholesterol used for?
Repairing plasma membranes, synthesising steroid hormones and bile salts.
What is the function of HDLs?
Reverse cholesterol transport, remove excess cholesterol and transport it to the liver.
What is the function of Apo C-2?
Apo C-2 activates the enzyme endothelial lipoprotein lipase, which breaks down TAG in chylomicrons and VLDLs to produce free fatty acids.
What is the function of Apo E?
Apo E is the docking protein for chylomicron remnants to be taken up into hepatocytes by receptor-mediated endocytosis.
What is the function of Apo B-100?
Apo B-100 is the apoprotein on LDLs, and is the docking protein that binds to LDL receptors so that LDL is taken up by cells by receptor-mediated endocytosis. The cholesterol ester is then broken down inside the cell to supply the cell with cholesterol.
What is a coated pit?
Region of plasma membrane specialised for receptor-mediated endocytosis.
What is the only way to remove cholesterol from the body?
HDL takes cholesterol from extrahepatic tissues to liver by reverse cholesterol transport, liver converts it into bile salts. small portion of bile salts excreted in the faeces each day.
What is newly formed HDL?
Discoidal HDL produced by liver and intestine - a disc of phospholipid bilayer enriched with the apoproteins LCAT and A-1.
Which transporter does discoidal HDL interact with so that cholesterol is pumped out of cells?
What is the function of LCAT?
Converts cholesterol (amphipathic) to cholesterol ester (non polar) so that it can be stored between the two layers of the bilayer disc - swelling them out to form a spherical lipoprotein particle.
What happens after HDL3 is converted to HDL2 after taking up more cholesterol ester?
HDL2 is taken up into the hepatocytes by receptor-mediated endocytosis at SR-B1 receptor, then hepatic lipase converts cholesterol ester back to cholesterol, then cholesterol converted to bile salts.
What does LCAT stand for?
Lecithin Cholesterol Acyl Transferase.
Which enzyme do cells use to synthesise cholesterol directly from acetyl coA?
HMG CoA reductase (the enzyme statins inhibit).
What forms the plaques in coronary heart disease?
Macrophages have a "scavenger system" so their uptake of LDL can't be regulated. They become saturated with cholesterol ester, the cells die and plaques form.
How do cells regulate their cholesterol level?
Inhibit HMG CoA reductase, or inhibit synthesis of LDL receptors.
Name the major function of white adipose tissue.
Releases fatty acids for use for energy during exercise and starvation.
Why does the blood glucose level not drop to zero during starvation?
Glucose is a universal fuel for all cells - it is needed by the central nervous system and used for aerobic glycolysis in cells that lack mitochondria like erythrocytes and retina cells. Fatty acids CAN'T cross the blood-brain barrier, so can't be used by the CNS, and fatty acids can't be used in respiration except in mitochondria, so can't be used by erythrocytes. Ketone bodies are used to fuel the CNS also.
Name two main ketone bodies.
Acetoacetate, and 3-hydroxybutyrate.
What produces the sweet smelling breath of a patient with very high ketone body concentration (e.g severe diabetic)?
Acetoacetate spontaneously decarboxylating to acetate.
Name the hormone that controls glucose entry into cells.
What is insulin's role in the glucose-fatty acid cycle?
When glucose levels increase, insulin inhibits lipolysis and stimulates glucose uptake into white adipose tissue for conversion to pyruvate and oxidation and also conversion to TAG and storage. Insulin also stimulates glucose uptake into muscle cells.
What happens when blood glucose level decreases?
The hormones adrenaline, noradrenaline, growth hormone, and glucagon all stimulate lipolysis and the secretion of fatty acids into the blood for oxidation and energy release. The level of insulin in the blood decreases, which decreases entry of glucose into the cells, so the blood glucose level does not drop to zero.
Which enzyme is not found in white adipose tissue, which means that a fall in blood glucose level will lead to an increase in free fatty acid level in the blood?
What's different about brown adipose tissue?
It generates heat in neonates (who can't shiver). It has lots and lots of mitochondria (appears brown due to the iron in the cytochromes in the mitochondria), and it has a special protein channel called thermogenin, which opens to uncouple oxidative phosphorylation. It's under nervous, rather than hormonal, stimulation. It's very vascular - to distribute heat around the body.
What factors regulate the rate of gastric emptying into the small intestine?
1) Presence of fats, protein, or very acidic chyme in the stomach promotes pyloric contraction and delays emptying.
2) Presence of 2-monoacylglycerol and fatty acids in the duodenum stimulate the release of CCK and GIP which delay gastric emptying.
3) Products of protein digestion delay emptying via endocrine pathways.
4) Gastrin released from G cells in the antrum and duodenum in response to peptides promotes contraction of the pyloric sphincter and delays emptying.
5) When acidic chyme enters the duodenum it stimulates secretion of secretin which delays gastric emptying by inhibiting contraction of the pyloric antrum.
What is the function of HDL?
Reverse cholesterol transport (from peripheral tissues to liver), and acts as a reservoir of apolipoproteins for VLDL and chylomicron metabolism.
How does high plasma LDL cause angina?
Macrophages take up LDL via scavenger receptors, and this process can't be regulated. If the macrophages get overloaded then they form foam cells which are a major component of atheromatous plaques.
Why are statins effective?
They inhibit HMG-CoA reductase, which is the rate-limiting enzyme in the synthesis of cholesterol.
How is the HMG-CoA reductase enzyme regulated?
The cell can regulate expression of the HMG-CoA reductase gene, via a transcription factor.
Also, the enzyme can be phosphorylated or dephosphorylated. The phosphorylated form of the enzyme is inactive, the dephosphorylated form is active. Insulin increases the activity of the enzyme, glucagon decreases it.
What is the channel called in brown fat cells that allows oxidative phosphorylation to be "unhooked"?
How do fibrates lower blood lipids?
Reduce transcription of the lipoprotein lipase gene.
Why does cholestasis lead to post-hepatic jaundice?
The bile is regurgitated into the serum, leading to increased conjugated bilirubin in the serum and dark urine (and raised ALP).
What does it mean if both ALP and GGT are raised in cholestasis?
The ALP is coming from the liver.
If ALP is raised and the calcium and phosphate levels are abnormal then the ALP may be coming from the bone.
If only ALP is raised then it is coming from the bile ducts.
What two things do we take in along with the bulk fat (triglycerides) in our diet?
Fat soluble vitamins (vitamins A, D, E, K)
Essential fatty acids (omega 3 and omega 6 - linoleic acid and linolenic acid)
Why is it important that products derived from milk are made up of short chain fatty acids?
They are small enough after hydrolysis by gastric lipase to be absorbed into the blood through the stomach wall - ready energy source for neonates.
Why do phospholipids in the membrane have one cis-unsaturated fatty acid?
So the core of the phospholipid bilayer is liquid and diffusion is more efficient.
What lipids are absorbed in the intestine along with triacylglycerol?
Phospholipids from animal and plant cell membranes, cholesterol esters from animal cell fat stores, cholesterol from animal cell membranes.
What property of TAG makes its digestion a challenge?
It is imiscible with water, and the digestive system is in aqueous phase.
What is emulsification?
Breaking up the globule formed by TAG in water (bulk lipid phase) into tiny lipid droplets .
Bile salts and amphipathic lipids stop the lipids re-aggregating.
What are micelles?
The products of lipase digestion (2-monoacylglycerol, fatty acids) are solubilised by bile acids into micelles to uptake by enterocytes.
Name 6 types of enzymes degrading the lipids.
Lingual lipase, gastric lipase, pancreatic lipase, bile-salt activated lipase, phospholipase, cholesterol esterase.
Also churning and a 37 degrees temperature in the stomach.
Which hormone is released by the duodenum in response to chyme, and causes the gall bladder to contract and sphincter of Oddi to relax so bile is secreted into the duodenum?
Which of the ester bonds of TAG do gastric and pancreatic lipase quickly hydrolyse?
Ester bonds of carbon 1 and 3.
What are the main products of TAG digestion?
2-monoacylglycerol and fatty acids
What are the products of digestion of cholesterol esters?
Free cholesterol and fatty acids
Why do the micelles formed by bike salts make it easier for enterocytes to take up the products of lipase digestion?
There is a layer of unstirred water around the enterocytes, so bile salts solubilise the products and deliver them much faster to the micro villi so they can diffuse into the cells.
Where are 95% bile salts reabsorbed?
Where in the enterocyte 2-monoacylglycerol and fatty acids built back up into TAG and combined with phospholipids and proteins to form chylomicrons?
Smooth endoplasmic reticulum
Why can't TAG just be released into the blood?
It would re-aggregate and block blood vessels, it must be stabilised with proteins and a mono layer of phospholipids.
Where are chylomicrons remnants formed?
In the blood capillaries.
Where are very-low density lipoproteins formed?
Formed from chylomicrons remnants in the liver and intestines.
What are low-density lipoproteins formed from?
Where are high-density lipoproteins formed?
Liver and intestines.
How are chylomicrons metabolised?
They bind to proteoglycans on the luminal surface of the capillary, and are broken down by lipoprotein lipase to release fatty acids.
What does the exogenous pathway involve?
Dietary fat and cholesterol being broken down, entering the circulation, then going to the liver.
Happens after a meal.
What does the endogenous pathway involve?
Regulation of lipid and cholesterol levels in blood and cells.
Happens all the time.
Of the lipoproteins in the blood, which are the only ones that are only present in the blood after a meal because they are secreted by the enterocytes, and not the liver OR intestines like the others?
Chylomicrons and chylomicrons remnants.
What is the main lipid component of chylomicrons and of chylomicrons remnants?
Chylomicrons = triacylglycerol
Chylomicrons remnants = triacylglycerol, cholesterol ester, phospholipids
What's the main lipid component of LDL?
What's the main lipid component of HDL1 and of HDL2?
HDL1 = phospholipid
HDL2 = cholesterol ester
What lipid component is carried in the blood bound to albumin?
Where exactly are VLDLs synthesised?
In the smooth endoplasmic reticulum of hepatocytes, then released by exocytosis into the blood.
What is the difference between how chylomicrons are released from enterocytes and how VLDLs are released from hepatocytes?
Chylomicrons are too large to fit through the fenestrations in the capillary so have to be released into lymphatic vessels first, VLDLs are small enough to be released directly into the capillary.
What is HDL1?
Newly-formed discoidal HDL (a disc of phospholipid bilayer, enriched by proteins A-1 and LCAT)
How is HDL1 converted to HDL2?
LCAT converts cholesterol to cholesterol ester so it is hydrophobic instead of amphipathic and can be stored between the phospholipid bilayer. The cholesterol ester swells out the bilayer disc to become a spherical particle with a core of cholesterol ester and a surrounding phospholipid monolayer.
How do cells synthesise cholesterol?
From acetyl co-A, using the enzyme HMG-coA reductase.
How is cholesterol stored in cells?
As cholesterol ester.
How do the plaques form in coronary heart disease?
Scavenging macrophages become loaded with so much cholesterol ester that it kills the cells and plaques form.
What are the two ways cholesterol levels in cells can be regulated?
Inhibit HMG-coA reductase, to reduce cholesterol synthesis.
Inhibit LDL receptor synthesis to block cholesterol uptake.
Why can't LDL uptake be regulated in macrophages?
They have a scavenger system.
Name 8 ways to treat hypercholesterolaemia.
1) Statins - HMG-coA reductase inhibitor
2) Ezetimibe - blocks absorption of cholesterol by enterocytes
3) more dietary fibre - so more bile salts are excreted in faeces, and more cholesterol delivers back to liver (e.g Beta-glucans from oats)
4) nicotinic acid raises HDL
5) exercise raises HDL levels
6) fibrates alter transcription of lipoprotein lipase gene
7) red wine raises HDL
8) bile acid sequestrians - beads that bind to bile salts so more is secreted in the faeces