Lipids Flashcards
What are the primary functions of lipids in the body?
Energy storage, cell membrane structure, insulation, precursor to hormones
How are glycerolipids structured, and what are their primary functions?
Glycerolipids have a glycerol backbone to which one, two, or three fatty acids are attached via ester bonds, forming mono-, di-, or triacylglycerols. Their primary functions include energy storage and serving as components of cell membranes
What distinguishes glycerophospholipids from other lipids, and where are they found in the body?
Glycerophospholipids have a glycerol backbone with two fatty acids and a phosphate group
- structural components of cell membranes
Describe the structure of free fatty acids (FFAs)
FFAs have a carboxylic acid head and a hydrocarbon tail. In plasma, most are bound to albumin, especially during fat catabolism
How are fatty acids classified by chain length?
Fatty acids are classified as short-chain (≤6 carbons), medium-chain (8-14 carbons), or long-chain (>14 carbons)
Explain fatty acid nomenclature using the example 18:2n-6
18 is the number of carbons, 2 is the number of double bonds, and n-6 indicates the position of the first double bond from the methyl end
what is the formula for palmitic acid? what is another name for it?
16:0
-hexadecanoic acid
how does the miller and omega notation differ?
Miller: specifies positions of where the loast db starts from the carboxyl (acid) end
-For example, 18:2n-6 indicates a fatty acid with 18 carbons and the last double bond at carbons 12 (n = 18 ; 18-6 =12)
Omega: specifies position of the first double bond from the methyl (omega) end
-For example, 18:3n-3 denotes a fatty acid with 18 carbons and the first double bond located three carbons from the omega (methyl) end
How does hydrogenation affect fatty acids?
Hydrogenation adds hydrogen to unsaturated fats, altering their properties by changing double bonds and creating trans fats as a by-product, which can raise LDL cholesterol
how does saturation affect structure of fats in different T? why is this?
saturated fats are solid at room T whild unsaturated fats are typically liquid
-the unsaturation causes kinks in the structure and prevents the fat from fully packing into a solid, increasing fluidity
what kind of fat is palmitoleic acid? where is it found?
MUFA, omega 7
-marine animal oils, plant and animal oils
what kind of fat is oleic acid? where is it found?
MUFA, omega 9
-plant / animal fats
-* most common in humans
what kind of fat is linoleic acid? where is it found?
PUFA, omega 6
-plant oils (soybean, corn, safflower, canola, nuts/ seeds)
what kind of fat is alpha-linoleic acid? where is it found?
PUFA, omega 3
-seed oils
what kind of fat is arachidonic acid? where is it found?
PUFA, omega 6
-animal fats
what kind of fat is ecosapentaenoic (EPA) / docosahexanoic acid (DHA)? where is it found?
both omega 3 PUFA
-fatty fish / seafood
what kind of fat is myristic acid? where is it found?
saturated fat
-coconut oil, animal / plant oils
what kind of fat is palmitic acid? where is it found?
saturated fat
-animal / plant fats
what kind of fat is stearic acid? where is it found?
saturated fat
-animal fat, some plants
what kind of fat is arachidic acid? where is it found?
saturated fat
-peanut oil
what kind of fat is lignoceric acid? where is it found?
saturated fat
-natural fats and peanut oil
What are triacylglycerols (TAGs), and where are they stored?
TAGs, composed of glycerol and three fatty acids, are the main form of fat storage found in adipose tissue
what are common sources of saturated vs trans fat?
saturated: butter, bacon, lard, cream cheese
Trans: fried foods, margarine, baked goods
what reaction creates TAGs? what does it produce?
condensation reaction of glycerol + 3FA makes TAG + 3H2O
what types of TAGs are there?
Simple- 3 FA are the same
complex- atleast one FA differs
How does chain length and saturation affect lipid properties?
Shorter chains and more double bonds increase fluidity, while longer chains and fewer double bonds enhance stability and firmness
what type of fat is most susceptible to oxidation?
PUFA
what is expected of the structure of Sn-1 glycerophospholipids vs Sn-2?
Sn-1 typically saturated FA
Sn-2 typically unsaturated FA
what are the 5 majot classes of glycerophospholipids?
Phosphatidyl:
1) chlorine
2) ethanolamine
3) serine
4) inositol
5) glycerol
CLESING
What is the function of phospholipids (PPLs)?
cell membrane structure, intracellular messengers, emulsifiers in food processing
Describe the structure and function of cholesterol in the body
Cholesterol, found as free or esterified forms, modulates membrane properties and serves as a precursor for steroid hormones and bile acids
what is phytosterol?
plant source of sterol, similar to cholesterol
Name the five classes of steroid hormones derived from cholesterol
Androgens, estrogens, progestins, mineralocorticoids, and glucocorticoids
What role do bile acids play in fat digestion?
Bile acids, derived from cholesterol, emulsify dietary fats, aiding in their digestion and absorption in the intestine
How efficient is lipid digestion, and what form do most dietary lipids take?
Lipid digestion is highly efficient, with >90% of ingested fats as TAGs and only ~4% escaping in feces. Long-chain fatty acids are the most abundant in food
What roles do gastric lipase and lingual lipase play in lipid digestion?
These enzymes are crucial for triglyceride digestion in infants, as they have low pancreatic lipase activity. They hydrolyze fats at specific positions on glycerol
what is the major enzyme involved in TAG digestion? where is it activated?
pancreatic lipase
-intestinal lumen
-works on Sn1/Sn3
where and how does fat digestion occur?
begins in the mouth (lingual lipase) and stomach (gastric lipase) through chemical digestion
What is the role of cholecystokinin (CCK) in lipid digestion?
CCK is released in response to chyme, slowing gastric emptying and stimulating the gallbladder to release bile acids
How does emulsification facilitate lipid digestion?
Emulsification breaks large fat globules into smaller droplets, increasing the surface area for enzyme activity, primarily by bile saltse
what do TAGs breakdown into from digestion by pancreatic lipase?
2 monoglycerols + 1FFA
what do TAGs breakdown into from digestion by gastric lipase? what does it efficiently hydrolyse? why is this important?
attacks Sn3 to make 1,2-diacylglycerols + FFA
-hydrolyzes milk fat efficiently because infants lack pancreatic lipase
what drug inhibits gastric and pancreatic lipases?
orlistat
explain digestion of TAGs from the mouth to small intestine
1) Mouth: Initial Digestion by Lingual Lipase (Sn3)
-Breaks down to FFA and diglycerides
2) Stomach: Gastric Lipase Action (Sn3)
-Breaks down to FFA and diglycerides
3) Small Intestine: Main Site of Digestion
Phase 1: bile emulsification
-CCK stimulates bile secretion to emulsify fats increasing accessibility to enzymes
Phase 2: pancreatic lipase activity (Sn1/Sn3)
-pancreatic lipase binds to bile salts to breakdown TAGs and diglycerols into monoglycerides and FFA
What is the function of pancreatic phospholipase A2?
It hydrolyzes fatty acids at the sn-2 position of phosphatidylcholine(most abundant phospholipid) , producing lysophosphatidylcholine and a free fatty acid
How are cholesterol esters digested? Can they be absorbed intact? what is produced?
Pancreatic cholesterol esterase hydrolyzes cholesterol esters, converting them into free cholesterol + FFA
-cholesertol must be in the free form to be absorbed
Describe the absorption of lipids by enterocytes.
Lipids must cross the unstirred water layer via mixed micelles containing bile salts and lipids, facilitating their absorption by enterocytes
What are the 2 mechanisms of lipid uptake into enterocytes? what types of lipid do they transport?
1) passive diffusion
-glycerol and short/medium chain FA
2) Carrier mediated transport
-long chain FA, monoacylglycerols, cholesterol
What is the role of Niemann-Pick C1-like 1 (NPC1L1) protein?
NPC1L1 is a major sterol transporter involved in the uptake of cholesterol or phtosterols into enterocytes
What are phytosterols, and how do they impact cholesterol absorption? what are sources of them?
Phytosterols are plant-based compounds similar to cholesterol. They reduce cholesterol absorption by competing for incorporation into micelles and promoting cholesterol export
-found in vegetable oils, nuts and added to mayonaise and other spreads
what is the function of ABCG5 and ABCG8 in phytosterol action?
they are transporters responsible for export of plant sterols out of the intestinal lumen
how does the presence of plant sterols impact cholesterol absorption? what impact does this have on health?
In the intestine, they compete with dietary and biliary cholesterol for incorporation into micelles. By reducing the amount of cholesterol that gets incorporated into these micelles, plant sterols decrease the absorption of cholesterol into the bloodstream
-Cholesterol that is not absorbed is excreted in the feces
-plant sterols can lead to lower levels of LDL (“bad”) cholesterol in the blood
Explain the enterohepatic circulation of bile acids
Bile acids are stored in the gallbladder between meals and are relased into the intestine and recycled to the liver via the hepatic portal vein once no longer needed, reducing the need for new bile acid synthesis
Describe the monoacylglycerol pathway in enterocytes, where are the enzymes for this pathway found?
re-esterification of monoacylglycerols into diacylglycerols using MGAT and then into triglycerides using DGAT
-these enzymes are found in the membrane of the ER
What happens to cholesterol in enterocytes?
Cholesterol is re-esterified by cholesterol esterase and acyl CoA using the enzyme cholesterol acyltransferase (ACAT) to form cholesterol esters for incorporation into chylomicrons
How are phospholipids re-formed in enterocytes?
Lysophospholipids are reacylated to form complete phospholipids, contributing to cellular and chylomicron membranes
Summarize the transport of lipids from the enterocyte
Glycerol, short- and medium-chain fatty acids (soluble and can go directly to the liver) enter the hepatic portal vein, while triglycerides,
cholesterol esters, and phospholipids are packaged into chylomicrons and transported via the lymphatic system
What are the main classes of lipoproteins?
chylomicrons, very-low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL)
How is LDL formed, and what is its main function?
LDL is formed from the conversion of VLDL to IDL and then to LDL. Its main function is to deliver cholesterol to tissues
What are apolipoproteins, and why are they important?
proteins that bind lipids to form lipoproteins. They serve structural functions, facilitate lipid transport to receptors, and act as ligands for cell surface interactions
What are the main steps of lipoprotein metabolism?
1) Chylomicrons: Formed in the intestine, they transport dietary triglycerides and cholesterol to tissues. Lipoprotein lipase (LPL) breaks down their triglycerides, forming chylomicron remnants taken up by the liver.
2) VLDL (Very-Low-Density Lipoproteins): Produced by the liver, VLDL transports endogenous triglycerides and cholesterol. LPL converts VLDL to IDL (Intermediate-Density Lipoprotein) and then to LDL.
3) LDL (Low-Density Lipoproteins): Delivers cholesterol to tissues. Excess LDL can lead to plaque formation in arteries if not cleared effectively by LDL receptors.
4)HDL (High-Density Lipoproteins): HDL removes excess cholesterol from tissues and transports it back to the liver for excretion or recycling through reverse cholesterol transport.
How does the body regulate cholesterol synthesis? what regulates this?
through HMG CoA reductase, the rate-limiting enzyme in cholesterol production
- High levels of cholesterol inhibit this enzyme
- Low levels of cholesterol stimulate the enzyme
What role do LDL receptors play in cholesterol homeostasis?
it binds and internalizes LDL particles, reducing circulating cholesterol. The number of LDL receptors is regulated by cellular cholesterol levels
How do dietary intake and endogenous synthesis affect cholesterol balance?
Increased dietary cholesterol intake suppresses endogenous synthesis by downregulating HMG CoA reductase, while reduced dietary intake can increase synthesis to maintain sufficient cholesterol levels
What is the impact of statin drugs on cholesterol homeostasis?
Statins inhibit HMG CoA reductase, reducing cholesterol synthesis. This decreases intracellular cholesterol levels, leading to increased LDL receptor expression and greater clearance of LDL from the bloodstream
What role does HDL play in cholesterol homeostasis? how is cholesterol excreted?
HDL facilitates reverse cholesterol transport by collecting excess cholesterol from peripheral tissues and transporting it back to the liver for excretion
-Excess cholesterol is excreted through bile, where some are lost through feces
where does cholesterol synthesis take place?
cytosol, close to ER
Explain the reverse cholesterol transport process involving HDL
HDL transports cholesterol from peripheral tissues to the liver for excretion, helping to reduce cholesterol accumulation and providing protective effects against cardiovascular disease
How does bile contribute to cholesterol homeostasis?
Bile, derived from cholesterol, helps emulsify dietary fats for digestion and absorption.
Excess cholesterol is excreted through bile, which can be reabsorbed or lost in feces, aiding in cholesterol regulation
What is the ratio of synthesis vs excretion of biliary / dietary cholesterol?
they are made and excreted in almost equal quantities of ~1.2g/day
What are the key steps in lipoprotein metabolism?
1) Chylomicrons: Formed in the intestine to transport dietary triglycerides and cholesterol. They deliver triglycerides to tissues via lipoprotein lipase and become chylomicron remnants, taken up by the liver.
2) VLDL (Very-Low-Density Lipoproteins): Produced by the liver to transport endogenous triglycerides and cholesterol. They are converted to IDL and then LDL after triglyceride removal.
3) LDL (Low-Density Lipoproteins): Delivers cholesterol to peripheral tissues. High levels can lead to cholesterol buildup in arteries.
4) HDL (High-Density Lipoproteins): Collects excess cholesterol from tissues and returns it to the liver for excretion or recycling through reverse cholesterol transport.
what is the major organ of FA synthesis? where else does it occur?
liver
What is the first committed step in fatty acid synthesis?
The conversion of acetyl-CoA to malonyl-CoA by acetyl-CoA carboxylase (ACC)
-rate limiting step
How does malonyl-CoA regulate fatty acid oxidation?
inhibits carnitine palmitoyltransferase-1 (CPT-1), preventing the transport of fatty acids into mitochondria for oxidation
-ensures reciprocal regulation of synthesis in the cytosol and oxidation in the mitochondria
What role does citrate play in fatty acid synthesis regulation?
Citrate acts as a ‘feed-forward’ activator of acetyl-coA carboxylase
-indicates fed state, promoting FA synthesis
How is fatty acid synthase regulated? what factors will increase / decrease FAS?
primarily at the transcriptional and translational levels by factors like SREBP-1c (drives elongation) and ChREBP
increased FAS: fed state, CHO (upregulates SREBP & ChREBP)
decreased FAS: fasted state, PUFAs
why is fructose lipogenic?
it bypasses the PFK-1 regulatory step in glycolysis and is converted to intermediates that promote de novo lipogenesis such as glyceraldehyde and DHAP
explain the postprandial fat curve and how insulin resistance would impact it
Normal State: Postprandial triglycerides peak and gradually decline due to efficient breakdown and uptake
Insulin Resistance: Elevated and prolonged triglyceride levels due to impaired LPL activity, increased VLDL production, and continued lipolysis
what processes occur during the initial rise in the post prandial curve? which of these processes are seen in the highest amount? when does this change?
absorption, secretion/repackaging from intestinal enterocytes, secretion of chylomicrons / appearance in blood stream, initial hydrolysis of chylomicron and disposal of FFA from TAG and clearance
the absorption outweighs the other processes initially, until absorption slows down and hydrolysis/clearance will outweigh absorption, showing a decline in the curve
all processes are active but to different extents due to fed vs fasted state
how does the postprandial curve of a carb vs fat differ in the initial graph? why?
postprandial curve for a fat will have a slower peak due to the time it takes to metabolize the triglycerides to FFA by lipoprotein lipase
glucose shows a spike within minutes due to quicker metabolism
Where can Glycerol 3-phosphate come from for TG synthesis in the liver vs adipose tissue?
Liver: Glycerol 3-phosphate comes from glucose, pyruvate or phosphorylated glycerol
Adipose: Glycerol 3-phosphate only comes from glucose or pyruvate
-lacks glycerol kinase
What is the function of perilipin, and why is it important?
Perilipin coats lipid droplets in adipocytes, restricting access to lipases
-it helps regulate the mobilization and breakdown of fat to control lipolysis
how does perilipin act when it is phosphorylated vs unphosphorylated? what signals phosphorylation?
Unphosphorylated Perilipin: Coats and protects lipid droplets, preventing unnecessary or excessive triglyceride breakdown
-insulin
Phosphorylated Perilipin: Undergoes a conformational change that facilitates the recruitment and activation of lipases, allowing for controlled lipolysis
-glucagon / epinephrine
What happens to HSL activity during fasting?
activity increases due to the release of hormones like glucagon and epinephrine
-enhanced lipolysis and mobilization of FFA for energy
What happens to plasma fatty acids during fasting?
concentrations increase during fasting and decrease after meals, reflecting mobilization and utilization of stored fats
