Scholz: Lipid Metabolism

Question 1

Functional roles of lipids? [4]

Answer 1

Energy store, part of lipoproteins, essential/major part of cell membrane, precursor of signalling molecules

Question 2

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?

Answer 2

Prostaglandins, leukotrienes, thromboxanes

Inflammation responses, pain responses, coagulation of blood (thromboxanes), and others

Arachidonic acid (delta-4 derivative of eicosanoic acid)

Question 3

Name four of the important lipid classes in the human body. What are they used for?

Answer 3

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)

Question 4

Lipids are ___________ acids. They are long __________ chains with ________ ______ groups.

Answer 4

hydrocarbon, hydrocarbon, terminal carboxy

Question 5

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.

Answer 5

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)

Question 6

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?

Answer 6

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: C_10:0)

Question 7

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?

Answer 7

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)

Question 8

Common unsaturated fatty acids: 16, 18 [3], 20. Common names?

Short name conventions?

What is the pattern of melting points?

Answer 8

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)

Question 9

In unsaturated fatty acids, what is causing the melting point to get lower with increased number of double bonds

In simple notation (C_18:1 Delta⁵), where do you count from to determine double bonds? Which side of that carbon is the double bond on?

Answer 9

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)

Question 10

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?

Answer 10

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)

Question 11

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?

Answer 11

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)

Question 12

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?

Answer 12

95%

38kJ/g vs 14.8kJ/g

~12 hours vs ~12 weeks

Question 13

What is the name of fat cells? What are they mostly made up of?

What do the bile salts from the gall bladder do?

Answer 13

Adipocytes (fat droplets)

Emulsifies fat so that it can be transported across the intestinal epithelia

Question 14

Why can the brain not use fatty acids for energy? So what does it use in hypoglycaemia?

Answer 14

Can’t get pass blood-brain barrier. Emergencies: uses ketone bodies.

Question 15

What is the structure of phospholipids?

Answer 15

Glycerol with two tails, and phosphate/head group.

Question 16

Phospholipids: why is the phosphate and head group important?

Why is cholesterol considered a lipid?

Answer 16

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)

Question 17

What effect do cholesterol molecules have on membranes? Why?

Answer 17

They make them less ‘stiff’ - they interrupt hydrophobic interactions between lipid tails

Question 18

What major effect do different kinds of head groups in phosopholipids have?

What is another name for the head group phosphatidylcholine

Answer 18

Alters distribution between inner monolayer and outer monolayer depending on chemical identity

Lecithin

Question 19

Four important properties of cholesterol?

Answer 19

Important membrane constituent, precursor of steroid hormones, precursor of bile acids, involved in fat transport

Question 20

Before fatty acids can be oxidised, what two steps must happen? How does this occur?

Answer 20

Activation and transport to mitochondria

Fatty acids are activated by linking them to coenzyme A (FA + ATP + CoA <-> acyl-CoA + AMP + PP_i) in the cytosol

They are then transferred to Carnatine (-> acyl-Carnatine) and it is transported into mitochondria by carnatine carrier protein

Question 21

What is the process of removing carbon atoms from fatty acids (in mitochondria) called? How many steps does it have?

Answer 21

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)

Question 22

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?

Answer 22

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

Question 23

What is B-Oxidation regulated by?

Answer 23

Availability of free fatty acids in blood, cytoplasm, and mitochondria

Question 24

How is amount of free fatty acids in the blood controlled?

What inhibits this process?

Answer 24

Hormonal activation (eg: adrenaline, glucagon, noradrenaline) of triacylglycerol lipases in adipose tissue

Insulin (+ malonyl CoA inhibits transport of FAs in mitochondria)

Question 25

What reactions are important in fatty acid synthesis? [2]

Answer 25

Acetyl-CoA carboxylase reaction and fatty acid synthase

Question 26

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?

Answer 26

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

Question 27

Fatty acid synthase: basics of how it works?

Answer 27

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)

Question 28

What are the two main binding sites on the fatty acid synthase? What binds to what? Which one will the chain build up on?

Answer 28

KS (Acetyl CoA - chain builds here) and ACP (Malonyl CoA)

Question 29

What is the first step of the fatty acid synthase reaction?

Answer 29

Condensation

Question 30

What is the second step of the fatty acid synthase reaction?

Answer 30

Reduction

Question 31

Third Step of Fatty Acid Synthase reaction?

Answer 31

Dehydration

Question 32

Fourth step of fatty acid synthase reaction?

What happens lastly?

Answer 32

Reduction

Lengthened fatty acid chain moved to KS site, and another malonyl group is added to ACP site (and the process can continue)

Question 33

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?

Answer 33

3, 2

16

Question 34

What is combined to create a triglyceride? What type of bond?

Where is the non-FA component derived from?

Answer 34

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)

Question 35

What is the ‘intermediate’ in the synthesis of triglycerides? What enzyme adds fatty acid molecules?

Then what happens?

What could happen instead?

Answer 35

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…