Scholz: Lipid Metabolism Flashcards
Functional roles of lipids? [4]
Energy store, part of lipoproteins, essential/major part of cell membrane, precursor of signalling molecules
One of the roles of lipids is as a precursor of signalling molecules. Give examples of these molecule classes. [3]
What are they responsible for?
What are they derivatives of? Which is itself a derivative of?
Prostaglandins, leukotrienes, thromboxanes
Inflammation responses, pain responses, coagulation of blood (thromboxanes), and others
Arachidonic acid (delta-4 derivative of eicosanoic acid)
Name four of the important lipid classes in the human body. What are they used for?
Fatty acids (building blocks for triglycerides/phospholipids, and precursor to eicosanoids -> arachidonic acid -> signalling molecules), triglycerides (energy storage in fat), phospholipids (membranes), cholesterol (membranes, precursor for bile acids/steroid hormones, involved in fat transport)
Lipids are ___________ acids. They are long __________ chains with ________ ______ groups.
hydrocarbon, hydrocarbon, terminal carboxy
Lipids: hydrocarbon chains are normally what range of length? And the maximum?
Are they odd or even numbered normally? Why?
The molecule is amphipathic. Explain.
14-20, 36
Even (linked to synthesis - C2 acetyl CoA residues join together)
Carboxy group makes heads charged and polar (hydrophile). The tails are uncharged and unpolar (hydrophobic/lipophilic)
Common straight chain saturated fatty acids: 10, 12, 14, 16, 18, 20, 24. Systemic names?
How does melting point change as the hydrocarbon chain lengthens? Why?
What does the ‘short name’ format look like?
Decanoic/dodecanoic/tetradecanoic/hexadecanoic/octodecanoic/eiconasonic/tetracosanoic acid
Melting point increases(larger = more van der waals = more energy needed to separate)
C[number of carbons]:[saturation] (eg: C10:0)
What is an unsaturated or polyunsaturated lipid?
Is cis or trans more common around these double bonds? Where do we find the other?
Which polyunsaturated lipids are connected with wellbeing? What does the greek letter stand for?
Lipids with one or more double bonds
Cis (trans largely in artificially ‘hardened’ foods - not processed as well)
Omega 3 and 6 (omega = double bond is found X number of positions from terminal [omega] carbon)
Common unsaturated fatty acids: 16, 18 [3], 20. Common names?
Short name conventions?
What is the pattern of melting points?
Palmitotic/oleic/linoleic/linoleric/arachidonic
C[number of carbons]:[number of double bonds] Delta[Double bond locations]
More double bonds = lower melting point (less energy needed to melt), increasing chain length = increased melting point (more van der waals)
In unsaturated fatty acids, what is causing the melting point to get lower with increased number of double bonds
In simple notation (C18:1 Delta5), where do you count from to determine double bonds? Which side of that carbon is the double bond on?
Kinks in the fatty acid chain mean that the hydrocarbon tails do not interact as much as they would in a saturated molecule = easier to move the whole thing apart (and head into a liquid state)
From the carbon of the carboxylic acid as 1 (double bond is to the left - so in this case between carbon 5 and 6)
What are triglycerides/triacylglycerols?
What enzyme is used to break them down to free fatty acids when we need energy? What hormone sets off this process?
Three fatty acid chains bound to a glycerol molecule in an ester bond (the typical form that fat is ingested as)
Triacyl glycerol lipase (Adrenaline)
What groups are involved (glycerol + fatty acids) in forming triacylglycerols? What type of link?
Is the final molecule polar or non-polar or amphipathic? So how does it interact with water?
Hydroxyl groups of glycerol, carboxy groups off FAs = ester link
Molecule is now completely non-polar (hydrophobic) - it doesn’t mix with water (forms droplets)
Triglycerides: in terms of energy storage, how much is in the FAs?
How much energy in the average fatty acid? In glucose?
Healthy person: how long would energy from glycogen last? And from triglycerides?
95%
38kJ/g vs 14.8kJ/g
~12 hours vs ~12 weeks
What is the name of fat cells? What are they mostly made up of?
What do the bile salts from the gall bladder do?
Adipocytes (fat droplets)
Emulsifies fat so that it can be transported across the intestinal epithelia
Why can the brain not use fatty acids for energy? So what does it use in hypoglycaemia?
Can’t get pass blood-brain barrier. Emergencies: uses ketone bodies.
What is the structure of phospholipids?
Glycerol with two tails, and phosphate/head group.
Phospholipids: why is the phosphate and head group important?
Why is cholesterol considered a lipid?
Adds charges to the head (thus making it polar/hydrophilic) - also gives it detergent-like qualities (?) [also alters function in membrane]
It has a small hydrocarbon tail, but mainly it is because it often associates with lipids (even if the structure is very different)
What effect do cholesterol molecules have on membranes? Why?
They make them less ‘stiff’ - they interrupt hydrophobic interactions between lipid tails
What major effect do different kinds of head groups in phosopholipids have?
What is another name for the head group phosphatidylcholine
Alters distribution between inner monolayer and outer monolayer depending on chemical identity
Lecithin
Four important properties of cholesterol?
Important membrane constituent, precursor of steroid hormones, precursor of bile acids, involved in fat transport
Before fatty acids can be oxidised, what two steps must happen? How does this occur?
Activation and transport to mitochondria
Fatty acids are activated by linking them to coenzyme A (FA + ATP + CoA <-> acyl-CoA + AMP + PPi) in the cytosol
They are then transferred to Carnatine (-> acyl-Carnatine) and it is transported into mitochondria by carnatine carrier protein
What is the process of removing carbon atoms from fatty acids (in mitochondria) called? How many steps does it have?
Beta Oxidation (it is a four-step cycle that is repeated as many times as is needed - based on the length of the fatty acid… 2 carbons are moved at a time)
What are the four steps of B-oxidation called?
What else is created during this process? How are these recycled?
What is this process dependent on?
What process is used for fatty acid chains of 22+ carbons?
Dehyrogenation, hydration, NAD+ dependent dehydrogenation, cleavage of molecule into Acetyl-CoA and a fatty acid with two less carbons
Electron carriers (FADH and NADH), recycled through electron transport chain
Oxygen
Peroxysmal B-oxidation
What is B-Oxidation regulated by?
Availability of free fatty acids in blood, cytoplasm, and mitochondria
How is amount of free fatty acids in the blood controlled?
What inhibits this process?
Hormonal activation (eg: adrenaline, glucagon, noradrenaline) of triacylglycerol lipases in adipose tissue
Insulin (+ malonyl CoA inhibits transport of FAs in mitochondria)
What reactions are important in fatty acid synthesis? [2]
Acetyl-CoA carboxylase reaction and fatty acid synthase
What must happen to Acetyl CoA before it is linked to a growing fatty acid chain?
What prosthetic group is needed for the reaction? Why?
It must be activated - converted from Acetyl CoA to Maloynyl CoA by Acetyl CoA carboxylase (which adds a carbon dioxide to it)
Biotin - it is easier to attach the carbon dioxide to biotin, and then it can be transferred to the Acetyl CoA
Fatty acid synthase: basics of how it works?
Acyl and malonyl residues are linked to fatty acid synthetase, and then to each other (essentially a reverse of B-oxidation, with reduced electron carriers needed instead of created - and it uses 2 NADH instead of 1 NAD/FAD)
What are the two main binding sites on the fatty acid synthase? What binds to what? Which one will the chain build up on?
KS (Acetyl CoA - chain builds here) and ACP (Malonyl CoA)
What is the first step of the fatty acid synthase reaction?
Condensation
What is the second step of the fatty acid synthase reaction?
Reduction
Third Step of Fatty Acid Synthase reaction?
Dehydration
Fourth step of fatty acid synthase reaction?
What happens lastly?
Reduction
Lengthened fatty acid chain moved to KS site, and another malonyl group is added to ACP site (and the process can continue)
How many carbons are there in a malonate? How many are added to a growing fatty acid?
At what length does another enzyme take over from fatty acid synthase?
3, 2
16
What is combined to create a triglyceride? What type of bond?
Where is the non-FA component derived from?
Glycerol + 3 fatty acids (via ester bonds)
Glycolysis intermediate (reduction of DHAP -> G3P by glycerol 3 phosphate dehydrogenase) or direct use of glycerol (glycerol phosphorylated to G3P by glycerol kinase)
What is the ‘intermediate’ in the synthesis of triglycerides? What enzyme adds fatty acid molecules?
Then what happens?
What could happen instead?
Phosphatidic acid (glycerol 3 phosphate w/two fatty acids attached [by acyl transferase] at the bits of the glycerol molecule that still have hydroxyl groups)
Phosphatidic acid phosphatase removes phosphate group from G3P (leaving another free hydroxyl group). Acyl transferase then attaches third fatty acid.
If a head group was added instead, you’d have a phospholipid…
