Lipids

Question 1

3 sources of fats

Answer 1

Diet
De novo biosynthesis in the liver - (starting from new in the liver)
Adipocyte stores - they can be hydrolysed to give free fatty acids and glycerol

Question 2

Describe the process of lipid digestion

Answer 2

• there is a mix of free fatty acids, mono and diacylglycerols that are solubilised
• These then get taken up by the enterocytes within the intestine
• The lipid digestion by lipases form monoacylglycerols (MAG), diacylglycerols (DAG) and free fatty acids (FAs) which join Bile Salts, Cholesterol, Lysophosphatidic Acid and fat soluble vitamins to form mixed micelles.
• the mixed micelles are absorbed by enterocytes
• Triacylglycerols (TAGs) are resynthesised
• TAGs are packaged into chylomicrons which then enter the lymphatic system and join the circulatory system

Question 3

Describe beta oxidation

Answer 3

• Fatty acid -> acyl coA using 2 ATPs in outer mitochondrial membrane
  enzyme = acyl CoA synthethase
• the Acyl CoA enters the mitochondria from the outer mitochondrial membrane by carnitine shuttle
• Fatty acyl coA oxidised and FAD is reduced to FADH2
• the molecule produced is then hydrolysed
• the product is then oxidised so NAD+ –> NADH
• remove a molecule of acetyl coA by bringing in a molecule of CoA using beta- ketothiolase
• The remaining part of fatty acyl CoA which has been shortened by two carbons then repeats the cycle

overall the original fatty acyl CoA has been shortened by 2 carbons

• during each cycle 1 NADH and 1FADH2 are formed

Question 4

Overall equation for breakdown of palmitate

Answer 4

Palmitoyl coA + 7FAD + 7 NAD+ + 7H20 + 7CoA ——> 8 acetyl coA + 7 FADH2 + 7 NADH

Question 5

When can acetyl coA from beta oxidation enter TCA?

Answer 5

When beta oxidation and carbohydrate metabolism are balanced as oxaloacetate is needed

Question 6

Which 2 enzymes are involved in biosynthesis of lipids?

Answer 6

Acetyl coA carboxylase

Fatty acid synthase

Question 7

What happens if acetyl coA can’t enter TCA?

Answer 7

Produces:
Acetoacetate
D 3 hydroxybutyrate
Acetone

Question 8

Describe lipogenesis

Answer 8

Acetyl coA + HCO3 = malonyl coA using acetyl coA carboxylase
Transfer malonyl to ACP = malonyl ACP using malonyl-coA-ACP transferase
Transfer acetyl from acetyl coA to ACP = acetyl ACP using acetyl-coA-ACP transferase
Condensation of acetyl ACP and malonyl ACP = acetoacyl ACP
Reduction using ketoreductase
Dehydration using dehydratase
Reduction using Ebola reductase

Question 9

Differences between fat metabolism and synthesis

Answer 9

Synthesis = ACP and uses NADP as reducing agent, happens in ER and mitochondria 
Metabolism = coA and uses NAD+ and FAD as reducing agents , happens in mitochondria

Question 10

Lipogenesis equation

Answer 10

Acetyl coA + 7 malonyl coA + 14 NADP + 14H+ = palmitate + CO2 +6H2O + 8 coA + 14 NADP+

Question 11

Diseases to do with lipid metabolism

Answer 11

Medium chain acyl coA dehydrogenase deficiency (MCADD) 
- autosomal recessive 
- part of heel prick test
-  no fasting
- have a high carb diet 
Primary carnitine deficiency
- autosomal recessive
- carnitine supplements given

Question 12

what are saturated fatty acids like?

Answer 12

• they are completely saturated with hydrogen (there are no double bonds) they are straight
• solids

Question 13

what are unsaturated fatty acids like?

Answer 13

• they have double bonds which inhibit rotation, therefore, there are kinks in the chain
• these are liquids

Question 14

what are adipocytes?

Answer 14

in mammals specialised cells called adipocytes take on the role of fatty acid storage

Question 15

how does bile emulsify fats?

Answer 15

• bile salts are generated by the liver and stored in the gall bladder
• during digestion they are secreted into the intestine
• They emulsify fats and aid their absorption
• biles convert fats into a soluble form so that the lipases can start breaking them down

Question 16

what does a lack of bile salts cause?

Answer 16

• Lack of bile salts causes fats to pass through the digestive tract undigested and unabsorbed resulting in steatorrhea (fatty stool)

Question 17

what is the structure of bile and how does that relate to how bile works?

Answer 17

• bile salts have a hydrophobic face and hydrophilic face which allows the bile salts to interact with solute and triacylglyerols
• Bile salts present the hydrophobic face to the triacylglycerols and the hydrophilic face to the solvent.

Question 18

what is a mixed micelle?

Answer 18

A Mixed Micelle forms which is a mixture of triacyl-, diacyl-, monoacylglycerols and free fatty acids.

Question 19

why is having anhydrous food supplies needed?

Answer 19

• good way of keeping compact food stores for subsequent mobilisation when needed
• if stored as glycogen people would be much heavier as glycogen needs water to be soluble
• every gram of glycogen needs 2 grams of water

Question 20

what is orlistat?

Answer 20

reduces fat absorption by 30% which is almost completely excreted by the faecal route - treats obesity.

Question 21

compare caloric yield of fatty acids and carbohydrates?

Answer 21

• The caloric yield of fatty acids is about double that of carbohydrates
• More than half the body’s energy needs (including the liver but NOT the brain) comes from the oxidation of fatty acids.

Question 22

how can acetyl CoA enter the TCA cycle?

Answer 22

• can only enter is beta oxidation and carbohydrate metabolism are balanced
• this is because oxaloacetate is needed for entry of acetyl CoA into the TCA cycle

Question 23

what happens is fat breakdown predominates carbohydrate metabolism?

Answer 23

If fat breakdown predominates (e.g. when fasting/starving), acetyl CoA forms:
• Acetoacetate
• D-3-hydroxybutyrate
• Acetone

Question 24

how many of what kind of bond generate the Acyl CoA from the fatty acid?

Answer 24

2 phosphoanhydride bonds

this is the same as ATP

these are needed to start off the reaction

Question 25

how does the Carnitine Shuttle | work?

Answer 25

- the species is firstly coupled to a molecule of carnitine (catalyst = Carnitine Acyltransferase I) to form Acyl Carnitine - Acyl Carnitine is then transported across the membrane by a translocase - Carnitine Acyltransferase II then removes the acyl group from acyl carnitine and passes it on to CoA to form Acyl CoA and reform carnitine. - The carnitine is moved back across the membrane to the cytoplasmic side by a translocase to pick up more Acyl CoA

Question 26

net ATP production of palmitate B oxidation?

Answer 26

You get far more ATP from fatty acids compared to from glucose metabolism

Question 27

what enzymes does fatty aid biosynthesis involve?

Answer 27

- Acetyl CoA Carboxylase | - Fatty Acid Synthase (FAS)

Question 28

how are fatty acids formed?

Answer 28

decarboxylative condensation reactions involving the molecules Acetyl-CoA and Malonyl-CoA.

Question 29

what does the fatty acid undergo after elongation?

Answer 29

- the fatty acid undergoes reduction and dehydration Ketoreducatase (KR) Dehydratase (DH) Enol Reductase (ER

Question 30

what is the lipogenesis process?

Answer 30

- first acetyl CoA is converted to malonyl CoA using the enzyme Acetyl CoA carboxylase - malonyl is transferred from malonyl CoA to the Acyl carrier protein to make malonyl - ACP. - Transfer of acetyl from a CoA species to acyl carrier protien (ACP) to form Acetyl-ACP (catalysed by Acetyl-CoA-ACP Transferase)

Question 31

what happens to the acetyl ACP?

Answer 31

- acetyl ACP is condensed with malonyl ACP to make 4C species acetoacyl - ACP

Question 32

what are the differences between fatty acid synthesis and fatty acid degredation?

Answer 32

Differences: • Carriers: CoA v ACP • Reducing Power: FAD/NAD+ v NADPH

Question 33

what are Acyl-CoA Dehydrogenases ?

Answer 33

* family of enzymes - there are different types of enzymes for the different lengths of fatty acid chain. * 5 types: 3-hydroxy, Short, Medium, Long, Very Long

Question 34

what is MCADD?

Answer 34

- Autosomal Recessive - occurs predominantly in caucasians. - 1/ 10,000 - accounts for 1/100 sudden infant death - If diagnosed - avoid fasting and have a rich carbohydrate diet - part of heel prick test - patients must make sure thir body is not dependent upon fatty acids for energy

Question 35

what is a primary carnitine deficiency?

Answer 35

- Autosomal recessive - Carnitine is needed to chaperone the Acyl group into the mitochondrial matrix from the outer membrane of the mitochondrion. - Carnitine can be given as a supplement to treat this deficiency.