Lipids %% IA (+- Flashcards
1
Q
What are lipids
A
- Heterogeneous (wide ranging) organic molecules
- Insoluble in water (hydrophobic), soluble in organic solvents
- Exist in cell membranes, as lipid droplets in adipose tissue, in blood lipoproteins
2
Q
Fuctions of lipids
A
- Stored form of energy
- Structural element of membranes
- Enzyme cofactors
- Hormones
- Vitamins A,D,E,K ►
- Signalling molecules
3
Q
Lipid classes
A
- Fatty acids
- Triacylglycerol
- Phospholipid
- Glycolipid
- Steroids
4
Q
Saturated & Unsaturated Fatty acids
A
- Unsaturated FA – one or more double bonds that kink the hydrocarbon chain, liquid (low Tm)
- Saturated FA are solid, no db (High Tm)
5
Q
Types of fatty acids
A
- Essential fatty acids: Linoleic and a-linolenic; must get these from plants
- “good fats (cardiovascular)”: high in polyunsaturated fatty acids: e.g. vegetable oils, like olive oil, sunflower oil, etc
- “bad fats (cardiovascular)” high in saturated fatty acids: e.g. stearic (beef). (Saturated -huge role in myelination of nerve fibres and hormone production important in maintaining health).
- “really bad fats”: trans fatty acids, result from hydrogenation of vegetable oils e.g. hard margarine (man-made)
6
Q
Essential FA’s
A
- Linoleic and linolenic acids are essential FA in humans
- Humans cannot introduce double bonds beyond carbon 9
- Must ingest essential FA
- Arachidonic acid, a precursor of eicosanoids can be synthesized from linoleic acid
7
Q
Omega 3 FA
A
- Omega-3 fatty acids are derived from linolenic acid as essential FAs.
- Omega-3 FA lowers plasma cholesterol prevents atherosclerosis, lowers TAG, prevents obesity, reduces inflammation.
- Omega-6 FA derived from linoleic are essential but not same benefits
8
Q
Triglycerides
A
- Esters of FAs and glycerol
- Esters are neutral uncharged lipids
- Water insoluble TAG coalesce into lipid droplets in adipose tissue (major lipid component of adipose tissue)
- Dietary fuel and insulation
9
Q
Phospholipids
A
- Composed of glycerol bonded to 2 fatty acids and a phosphate group.
- Amphipathic - charged phosphate group ‘head’ of a phospholipid is hydrophilic (attracted to water) whereas the hydrophobic ‘tails’ repel water.
10
Q
Digestion and absorption of lipids
A
- Triacylglycerol main dietary lipid
- Others: phospholipids, cholesterol, cholesterol ester, free fatty acids
- Small intestine main site of digestion
- Most TAG degraded in small intestine by pancreatic lipase to monoacylglycerol + 2 FA
- Lipid digestion by pancreatic enzymes (lipases) is promoted by emulsification (dispersion) by bile salts and peristalsis (mixing)
- Cholesterol esters digested to cholesterol and free FA
- Phospholipids hydrolysed to FA and lysophospholipid
11
Q
Bile salts
A
- Act as biological detergents to form emulsions and mixed micelles
- Saves lipids coalescing in an aqueous environment
- Derivatives of cholesterol
12
Q
Uptake of digested lipids
A
- Products of lipid digestion form mixed micelles with bile salts. Mixed micelles approach brush border membranes (microvilli) of enterocytes (intestinal absorptive cells) and release (long) lipid products which enter cells by diffusion.
- Short and medium chain FA do not require micelles for absorption
13
Q
Steatorrhea
A
- Lipid malabsorption due to defects in bile secretion, pancreatic function or intestinal cell uptake results in steatorrhea
- Steatorrhea is excess fat in faeces. Stools float due to excess lipid, have an oily appearance and are foul smelling
- Gallbladder secretes bile. Removal of the gallbladder inhibits digestion and absorption of fats
14
Q
Lipid utilisation
A
- Intestinal cells resynthesize TAG, PL, CE for export
- insoluble so packaged with apoB-48 (solubilising protein) into chylomicrons for export
- Chylomicrons are released by exocytosis into lymph then blood
15
Q
What happens when blood chylomicrons reach tissue?
A
- TAG in chylomicrons is hydrolysed to FA and glycerol by lipoprotein lipase
- Lipoprotein lipase is found primarily in capillaries of skeletal muscle and adipose tissue
- Resulting free FA used for energy or re-esterified to TAG for storage
- Chylomicrons depleted of TAG are called chylomicron remnants – go to liver
- Glycerol is used by liver to produce glycerol-3-phosphate (glycolysis & gluconeogenesis)
16
Q
Summarisation
A
17
Q
Lipoproteins
A
TAGs, and cholesterol esters are insoluble in water and cannot be transported in blood or lymph as free molecules
Hydrophobic cores : TGs , cholesteryl esters cores:
Hydrophilic surfaces : unesterified cholesterol, phospholipids , apolipoproteins e.g.B100
18
Q
Densities
A
Least to most dense:
- Chylomicrons –TAG rich (TAG from intestine to tissues).
- VLDL –TAG rich (TAG from liver to tissue)
- LDL – cholesterol rich (cholesterol to extrahepatic tissue – BAD cholestero )
- HDL – protein/cholesterol rich. (Transports cholesterol from tissue to liver for elimination–GOOD cholesterol )
19
Q
B-oxidation of FAs overview
A
- The β-oxidation pathway degrades fatty acids 2 carbons at a time
- Produces acetyl CoA and also NADH and FADH2 which are sources of energy (ATP)
- Occurs in mitochondrial matrix
- 3 stages: activation, carnitine shuttle, degradation
20
Q
Stage 1: FA Activation
A
•Fatty acid activated to form fatty acyl CoA in cytoplasm
21
Q
Stage 2: Carnitine Shuttle
A
- The carnitine shuttle is responsible for transferring long-chain fatty acids across the barrier of the inner mitochondrial membrane to gain access to the enzymes of beta-oxidation.
- Carnitine fatty acyl-transferase (CAT-1) is inhibited by malonyl CoA
- Prevents synthesis and degradation occurring simultaneously
- Carnitine from diet or made from lysine or methionine (liver/kidney)
22
Q
Stage 3: Degredation
A
- Dehydrogenation to produce FADH2 aka oxidation (FAD → FADH2) for ATP formation
- Hydration
- Dehydrogenation to produce NADH aka oxidation (NAD+ → NADH) for ATP formation
- Thiolysis (cleaved) to produce acetyl CoA go feed into the Krebs cycle
23
Q
ATP yield
A
Total ATP molecules formed: 129
FADH2 – 2 ATP x 7 = 14
NADH – 3 ATP x 7 = 21
Acetyl CoA – 12 ATP x 8 = 96
TOTAL = 131
However, 2 ATP are needed in production of palmitoyl CoA, so
TOTAL = 129 ATP
(32 ATP from 1 glucose molecule)
•
24
Q
Fasting/starvation
A
- liver flooded with acetyl CoA from FA breakdown
25
Q
Fasting and ketone bodies
A
- During fasting or starvation, glucose is decreased, and excess acetyl CoA from fat metabolism can be converted to ketone bodies
- Cardiac and skeletal muscles use ketone bodies as an energy source.
- Ketone bodies can fuel brain cells during starvation (Brain cannot use FA as fuel source)
26
Q
Ketone bodies
A
- Formed in the mitochondrial matrix of liver and is transported with the blood to other cells where it is used as fuel.
- Liver makes but cannot use ketone bodies
- Uncontrolled diabetes (or starvation) leads to very high ketone body concentrations in the blood.
- When the rate of ketone body production exceeds utilisation, ketonemia (blood KB), ketonuria (urine KB) and acidemia results
- Fruity odour in breath due to acetone results
27
Q
When does Diabetic ketosis occur
A
- a dangerous complication faced by people with diabetes which happens when the body starts running out of insulin.
- When insulin is absence
28
Q
Synthesis of FA
A
- FA synthesised from acetyl CoA, derived from excess protein, fat and carbohydrate
- CoA cannot cross mitochondrial membrane (only “acetyl” part can cross)
- Uses ATP and NADPH
- Sythesis occurs in cytosol
- Acetyl CoA formed in mitochondria so needs transferred to cytosol
29
Q
FA Synthesis and degradation similarities and differences
A
Note: FA synthesis and degradation do
not runat the same time
30
Q
Table
A
31
Q
Specialised Lipid classes
A
- Steroid hormones are chemical substances that serve as chemical messengers in the body
- Cholesterol is the starting material for the synthesis of steroid hormones.
- Eicosanoids are derived from 20-carbon unsaturated fatty acids (eicosanoic acids) and are synthesized throughout the body
32
Q
Sterols: cholesterol
A
33
Q
Eicosanoids regulation►►
A
- Inflammatory response (Leukotrienes )
- Pain & fever (Prostaglandins)
- Blood pressure regulation (prostacyclin)
- Blood clotting induction (thromboxanes)
- Many reproductive functions (e.g. labour induction) & menstrual cramps (prostaglandins)
- Sleep/wake cycle
34
Q
Fatty acid nomenclature
A
18: 0 – contains 18 carbons and no double bonds
18: 1 – 18 carbons and one double bond
