24 Flashcards
Two examples of molecules associated with fat metabolism
- Triacylglycerol (has a 3 carbon glycerol back bone component, 3 lipid long chain fatty acid units (vary in chain length) - esterified to glycerol backbone - acyl functional group )
- Cholesterol ester (4 carbon rings with carbon structure extension, ester variant version shown, R represents a long carbon chain, cholesterol is often eaterified to various long chain fatty acids
What sulbuises fat in the GI tract?
Bile acids (bile salts) solubilize fat in the gastrointestinal tract
(- facilitates the breakdown of tryirsalgylceral into fatty acids and a glycerol derivative component do it can be taken into the body)
Fat molecules are not typically
Soluble (unless highly modified with charged groups)
One side of a bile salt is _____ the other side is _____
Hydrophilic
Hydrophobic
What are bile salts synthesised from and where are they synthesised and then where are they stored and as what are they stored as?
synthesised from cholesterol in liver and stored in gall bladder as bile
Where are bile acids/salts secreted into and in response to what
Secreted into small intestine in response to cholecystokinin
Bile acids/salts are powerful ________ with _______ and ______ surfaces
Are powerful detergents with hydrophobic and hydrophilic surfaces
(Biphasic)
What do bile acids form and why?
Form micelles with triacylglycerols to increase surface area for digestion
(Micelles - hydrogphob core and external surface is hydrophilic )
What does bile contain
Water
Bile acids
Electrolytes
Phospholipids
Cholesterol (= Gall stones)
Bile pigments ie bilirubin, biliverdin - breakdown of haem, recycled via liver)
If cholesterol too high
Gall stones - insoluble
How bile acids are made from cholesterol - diagram
Hydroxyl group at the end of cholesterol…
… could in some cases by esterirfied with varies chain length fatty acids to make a cholesterol ester
Bile salts all vary in terms of their…
…functional groups
Two random examples of bile acids
- glycocholic acid
- taurocholic acid
(Drriviates of basic choletestol building block)
Where is bile synthesised ?
In the liver
Where is bile stored?
Gall bladder
What is the image of
( - higher cholesterol input into the diet = posibility for forming insoluble inclusion bodies )
Gall stones
Digestion is regulated by?
Peptide hormones
Examples of peptide hormones (short amino acid sequences)
What hydrolyses triacylglycerols to free fatty acids and 2-monoacylglycerol
Pancreatic lipase
What does Pancreatic lipase do
Pancreatic lipase/colipase system hydrolyses triacylglycerols to free fatty acids and 2-monoacylglycerol
Pancreatic lipase/collipase enzyme system hydrolyses triacylglycerols to free fatty acids and 2-monoacylglycerol - diagram, what does R1, R2 and R3 mean
What forms after Pancreatic lipase/collapse enzyme system hydrolyses triacylglycerols to free fatty acids and 2-monoacylglycer (absorbtion)
Smaller micelles form containing bile salts, free fatty acids, monoacylglycerol (and cholesterol)
Micelles are absorbed across intestinal cell membrane
What do we need to enhance activity of lipase
Co-lipase
2-monoacylglycerol
1 fatty acid chain
Bile salts ____ triacyglycerols and assist with ___
Bile salts solubilize triacylglycerols and assist with hydrolysis
Bile salts solubilize triacylglycerols and assist with hydrolysis
- DIAGRAM - plus yappage
Once in micelle, pancreatic lipase can interact with other molecules and project in the catalytic active site of enzyme enabling hydrolysis of triaglycerol inside this structure
(Need to be hydrolysed to be taken into the epithelial cells to then by transported into and around the body)
Absorption of products from the gastrointestinal tract into the bod - what features of the intestine assist with the absorbtion
The small intestine has specialised structures that create a vast surface area for absorption.
Villi
Microvilli (brush border)
(Both increase SA)
(All molecules not just lipids are absorbed here)
What does fat malabsorption leas to…
… excess of fat and fat-soluble vitamins in faeces
What is fat malabsorption caused by
conditions that interfere with bile or pancreatic lipase secretion, ie. pancreatitis, gall bladder or liver diseases
What is a potent inhibitor of pancreatic lipase
Xenical (Orlistat)
How Xenical (Orlistat) accts as an inhibitor of pancreatic lipase
- compound acts as an inhitibotr by covaletnly bonding to a functional group neat the lipase active site thus blocking the lipase active site
Overview of lipid processing in the gastrointestinal tract
- diagram
BILE SALTS ARE REABSORBED AND RECYCLED TO THE LIVER
- FA are put back into TG for transport ?? Into chylomicros then into the blood and circled around the body)
What do lipoproteins do?
- Help ‘solubilise’ lipids for transport in blood to tissues
- Provide a ‘delivery system’ for transporting lipids into and out of cells
What are the function of apoproteins (lipoproteins) accessory lipoproteins..?
- structural for assembly (apoB)
- ligands for cell surface receptors (apoE and apoB)
- enzyme cofactors (apoCII for lipoprotein lipase)
General lipoprotein structure
- phospholipids/proteins have hydrophilic head and hydrophobic tails
Four main lipoprotein classes
- chylomicrons
- very low density lipoproteins (VLDL)
- low density lipoprotein (LDL)
- high density lipoproteins (HDL)
Once fatty acid and MG has been transported across the epithelial tissue… its put back into triaclyglycerol so that they can by put into the chylomicorns for shipping- what does triaclyglycerol synthesis look like?
- progressive addition of fatty acids onto strucuture forming tryclyglycerol
- fatty acids are activated with CoA to achieve the reaction sequence
- occurs in the epithelium
What is CoA (Coenzyme A) synthesised from?
pantothenate (Vit b5), ATP and cysteine
(YAP) Classically 4 lipoprotein classes were identified using…
- electron microscopy looking at overall structures
- But more commonly now they are identified based on density as a result of ultracentrifuging
- going down the table
- going down the table desensitised increases
- TAG decreases down the table (TAG is low density)
- protein increases
What does it mean if LDL is high
- high cholesterol
- can lead to arterial skerosis (yap)
The reason the different lipoproteins vary in density is due to the ratios of their components
Yes?
- this kinda thing will be in exam
How can lipoprotein composition be analysed?
Lipoprotein composition in clinical plasma samples can be analysed by native (non-denaturing) gel electrophoresis
A densitometry scan of the lipoprotein gel provides another way of comparing normal vs. abnormal lipoprotein profiles
Blood lipid profile - what do labs typically measure -
Typically, labs measure total cholesterol, high density lipoprotein (HDL) and triglycerides (triacylglycerols) – used to identify dyslipidemia
How can LDL be measured
Low density lipoprotein (LDL) can be estimated from [total cholesterol – HDL – triglyceride/5], but different calculation methods give different results
- will b in exam
How can VLDL be estimated ?
VLDL can be estimated from VLDL = [triglyceride/5]
Two major lipid transport pathways:
‘Exogenous’ chylomicron pathway (dietary fat)
‘Endogenous’ VLDL/LDL pathway (endogenously synthesised fat)
Wtf is this diagram
Inherited lipid disorders
What is lipoprotein lipase?
- enzyme found on the endothelial surface of capillaries
What does Lipoprotein lipase do?
Hydrolyses TAG in lipoproteins to 2-monoacylglycerol and fatty acids - highest activities in heart and skeletal muscle and adipose tissue
Lipoprotein lipase is activated by…
apoCII
What leads to elevated levels of chylomicrons and plasma triacylglycerol
Defects (by mutation) in either apoCII or lipoprotein lipase
What do Defects (by mutation) in either apoCII or lipoprotein lipase lead to?
elevated levels of chylomicrons (as their not being processed efficiently as they come into the circulation) and plasma triacylglycerol
Where is Lipoprotein lipase activity highest
in heart and skeletal muscle and adipose tissue
Patients with high blood triglyceride levels can be treated wit…
‘Tricor’ (Fenofibrate)
Patients with high blood triglyceride levels can be treated with ‘Tricor’ (Fenofibrate) - what does ‘Tricor’ (Fenofibrate) do?
(upregulates lipoprotein lipase via activated peroxisome proliferator-activated receptors alpha (PPAR-alpha), and induces HDL synthesis) - (via liver reporeocessing system)
What is Familial hypercholesterolemia (FH)
Common form of hyperlipidaemia which leads to
premature atherosclerosis (thickening of arteries)
What is F amilial hypercholesterolemia (FH) caused by?
defect in LDL receptor gene (many different mutations)
Familial hypercholesterolemia (FH) is a dominant/ recessive disorder?
Dominant disorder i.e. heterozygotes affected
LDL levels of Familial hypercholesterolemia (FH) - what are they treated with ?
LDL (‘bad’ cholesterol) levels 2-3x higher than normal
Treated with ‘statins’ to lower LDL and increase HDL
(‘good’ cholesterol)
Xanthomas in FH patients
Fatty growths under the skin
