Flashcards in Metabolism of Fats Deck (66):
1
How much fat do we normally get in our diets?
100-150g
2
what % of our total dietary energy intake is fat?
40%
3
where does the fat in our diet come from?
milk and milk products, cheese, cream, butter,
margarines, cooking oils,
lard, meat fats, eggs,
cereal grains, nuts, fat-rich fish and fruit (avocado), etc
4
what is taken in with the fat
fat-soluble vitamins
A, D, E, K
5
what fatty acids come as part of the fat we take in?
the essential omega-6 and omega-3 fatty acids linoleic acid (C18:2 D9,12)
and linolenic acid (C18:3 D9,12,15) respectively
6
what is the main strucure that the main fats in cooking oils, butter, margarine, meat fat, cereal and nut oils all have in common
TAG or
TRIACYLGLYCEROL (triglyceride) in which three fatty
acids are ester bonded to glycerol.
7
what is a simpler form of TAG
Simpler forms with one or two acyl chains esterified to glycerol
8
what are the other lipids that get taken into the intestine in our food
along with the triacylglycerol
Phospholipids from cell membranes
Cholesterol esters from animal
cell fat stores
Cholesterol from animal
cell membranes
9
what is the problem with fat digestion, absorption
and transport
Fat (triacylglycerol, TAG) is immiscible with water!
10
TAG has to be digested in an aqueous environment, the intestine. What is the SOLUTION
emulsification into small droplets (1-100m) and their stabilisation by bile salts and amphipathic lipids for enzyme action
11
TAG has to be transported round the body in the blood, also an aqueous environment, What is the solution?
coat TAG-rich particles with protective proteins and amphipathic lipids
12
what are the basics of fat digestion. to include the emulsification bile salts lipases and bile salts again
Emulsification in mouth and stomach at 37oC liquifies and emulsifies the bulk lipid phase into small (1-100m) droplets. This increases the surface area of TAG droplets for enzyme attack.
Bile salts from gallbladder and amphipathic lipids coat small emulsion particles preventing them re-aggregating into bulk TAG phase
Lipases degrade TAG
Bile salts solubilise products of lipase digestion into micelles (nm size) to facilitate uptake into enterocytes in jejunum region.
13
what the 3 sources of lipid-degrading enzymes
Lingual lipase
Gastric lipase
Pancreatic triglyceride lipase
14
what are the Pancreatic triglyceride lipases
bile salt-activated
lipase, pancreatic lipase related protein 2,
phospholipases, cholesterol esterases
15
what are the Gastric lipases
lipase cleaves 15-20% of dietary TAG fatty acids. Especially important in neonate for milk TAG digestion. Churning action of stomach at 37oC emulsifies bulk TAG phase-very important!
16
what are the lingual lipases
from Ebner’s glands on
dorsal surface of tongue, activity continued
in stomach
17
The churning action of the stomach at 37oC emulsifies the
bulk TAG phase into small droplets 1-100 microns or less in
diameter. These have a much larger surface area for lipase
enzymes to act on. What prevents the small TAG particles from re-aggregating
into a bulk fat phase in the duodenum where mixing is not so active?
The particles become coated with bile salts and more amphipathic phospholipids and cholesterol. The more polar surface prevents small emulsion droplets from re-aggregating yet allows lipase action to degrade the TAG
18
Steps of lipid absorption
Breakdown of products of lipid digestion + amphipathic bile salts = micelles
Micelles travel to apical brush border of intestinal Epithelial Cells (Ecs) and release products for digestion
Once inside intestinal Ecs lipid products are re-esterified with FFA = PLs, CEs, TAGs
Re-esterified lipids + apo(lipo)proteins = chylomicrons
Chylomicrons migrate to basolateral membrane of the ECs of the small intestine and exocytosis occurs into the lacteals, the thoracic duct and ultimately the blood
19
Lipid absorption, re-esterification, and incorporation into chylomicrons in the small intestine.
Mixed micelles release their contents that enter intestinal epithelial cells. Bile salts are recirculated from the ileum to the liver via the enterohepatic circulation. C cholesterol, CE cholesterol ester, FFA free fatty acid, MG 2-monoacylglycerol, LL lysolecithin, PL phospholipid, TG triglyceride, VA vitamin A, VD vitamin D, VE vitamin E, VK vitamin K
20
You are asked to see Mr. Stephenson, a 49-year-old man with chronic pancreatitis secondary to alcohol abuse. While eliciting his GI review of symptoms, you note that he complains of greasy, diarrheal bowel movements.
Why?
Excessive alcohol consumption is the most common cause of chronic pancreatitis and a very frequent cause of pancreatic insufficiency.
Patients who suffer from chronic pancreatitis produce insufficient amounts of lipase which is crucial for the digestion of lipids.
Malabsorption of lipids results in the excretion of greasy stools or steatorrhea.
21
true or false, Bile is continuously formed by the liver and secreted to the gallbladder where it is stored and concentrated.
true
22
what are bile acids and what do they do
Bile acids are the
breakdown products
of cholesterol
They are conjugated
to glycine and taurine
making one end more
polar and are present
in bile as the sodium
and potassium salts.
They are powerful
detergents.
23
where are primary bile salts fromed and give examples
Cholic and chenodeoxycholic acids (and the corresponding
taurocholic acid, etc) are primary bile acids made by the liver
24
where are secondary bile salts fromed and give examples
are formed by bacterial action in the intestine and are secondary bile acids.
25
structure and consequential function of bile acids
Bile acids have a planar
structure with all polar
groups on one face and
non-polar groups on the
other face. So they are amphipathic, aggregate
into nm size micelles and
are good detergents.
26
how is some cholesterol excreted daily?
There is an enterohepatic
circulation of bile acids
with some being lost each day
in the faeces.
27
when is CCK Cholecystokinin released from the duodenal mucosa?
when food enters
the intestine
28
what does Cholecystokinin CCK do?
CCK in the blood stimulates
the gallbladder to release bile by contraction
of the gallbladder and relaxation of the
sphincter of Oddi which is normally closed
to prevent bile and hepatic secretions
flowing into the intestine until required.
29
what is cholelithiasis
stones in gallbladder
30
Choledocholithiasis
stones in ducts of biliary tree
31
Cholesterol stones
70-80% cholesterol
32
Pigment stones
bile pigments (bilirubin, billiverdin)
33
who is more at risk of kidney stones?
Caucasians, females, low fibre, high
cholesterol, starchy diet, overweight
34
true or false Most TAG is degraded to 1-monoacylglycerol with only a little glycerol being formed depending on how long food remains in the duodenum
Most TAG is degraded to 2-monoacylglycerol with only a little glycerol being formed depending on how long food remains in the duodenum
35
true or false Micelles of bile salts solubilise the fatty acids and 2-MAG from TAG degradation as well as lyso-lipids from phospholipid digestion and cholesterol. The mixed micelles transport
lipid digestion products to the
microvilli of erythrocyctes
Micelles of bile salts solubilise the fatty acids and 2-MAG from TAG degradation as well as lyso-lipids from phospholipid digestion and cholesterol. The mixed micelles transport
lipid digestion products to the
microvilli of enterocytes
36
what transport the products of fat digestion
across the unstirred water layer at the enterocyte surface
bile salt micellells
37
what woyld happen to 2MAG absportion with out bile salts
Without bile salts fatty
acids and 2-MAG are absorbed much more slowly.
38
what do bile salt micelles deliever?
products of fat digestion
across an unstirred water layer to the enterocyte
membrane where they are taken up by carrier-mediated and/or passive diffusion mechanisms
39
true or false, bile salts are not absorbed. They are transported to the ileum for reabsorption and recycling.
true
40
what happens to fatty acids and 2-MAG
they are reassembled into TAG,
some protein is added and the TAG is secreted as chylomicrons
41
wha tis the size of chylomicrons
75-1000nm in diameter
42
are Glycerol and short
chain fatty acids (C4-10)
are water-soluble and can they pass
through enterocytes
directly into the blood?
yes
43
where are absorbed products of fat digestio reassembled into TAG
in the endoplasmic reticulum of enterocytes.
44
what is added as
the TAG droplet passes from the
endoplasmic reticulum to the Golgi
where glycosylation of proteins
occurs.
Phospholipid and protein
45
how do chylomicrons enter the circulation and why
Chylomicrons are too big (up to 1m)
to pass into capillaries so enter the
circulation via the thoracic lymph duct
46
how does TAG
accummulate in the enterocytes.
Blocking protein synthesis
stops chylomicron release
47
Cholesterol, cholesterol ester
and fat-soluble vitamins are added
to the chylomicrons which move in
vesicles to the plasma membrane via what process
exocytosis
48
what is the structure of High density lipoproteins
disc-like shape
initially.
49
how do the rather similar struture of very low density liproptein differ
vary in the apoproteins
on the particle surface.
50
how do Chylomicrons transport dietary fat from intestine to tissues
via plasma
51
Chylomicrons transport dietary fat from intestine to tissues via plasma, what do other liproteins do?
circulate fat between tissues in the plasma
52
how does the colour of plasma change during and after eating a fatty meal?
After ingesting a fatty meal the plasma goes opaque with chylomicrons but
clears again in one to two hours as the chylomicrons are metabolised
53
importance of Omega 3 fatty acid
anti-inflammatory
polyunsaturation
control blood clotting
build cell membrane s in the brain
normal growth and develoment
roles in bp, rheumatoid arthritis and depression
54
importance of Omega 6 fatty acid
pro-inflammatory
polyunsaturated
brain function, normal growth and development
55
Fat (triacylglycerol, TAG) summary
is a major dietary component contributing to energy needs, also brings in fat-soluble vitamins and essential fatty acids
56
Chylomicrons summary
in the blood are stabilised by amphipathic apoproteins on their surface, phospholipids and some cholesterol and are only present in the blood after a meal (cleared in a couple of hours)
57
TAG summary
in chylomicrons is removed by lipoprotein lipase in capillaries in extrahepatic tissues: remaining TAG is taken up by liver for metabolism and recirculation
58
Enterocytes summary
reassemble 1-MAG and fatty acids back into TAG which is then secreted into lymphatics as big particles called chylomicrons - entering blood at thoracic duct
59
Digestion of fats presents problems due to
the fact that TAG is water-immiscible
60
Bile salt micelles summary
solubilise 1-MAG and fatty acids and transport them to enterocytes in duodenum and jejunum. 95% of bile salts are later reabsorbed in the ileum
61
Emulsification (mechanical disruption into tiny droplets) of fats occurs in
the stomach
62
Pancreatic TAG lipase summary
is the major enzyme digesting TAG mainly to 1-MAG (1-monoacylglycerol) plus two fatty acids (depends on transit time)
63
Fat emulsion particles summary
are stabilised in the duodenum by bile salts and other amphipathic lipid giving a large surface area for lipase enzymes to act on
64
Bile salts summary
derived from cholesterol metabolism are stored in gall bladder until needed
65
Actions of pancreatic lipase, bile salts and colipase in fat digestion.
(a) Pancreatic
lipases break down triglycerides. (b) Bile salts coat lipid droplet and displace lipases. (c)
Addition of colipases anchor lipases to bile salt-coated fat droplet (Adapted from American
66