Fatty acid catabolism and metabolism

Question 1

Why metabolise fatty acids? ( why store so much of our energy as fatty acids and triglycerides rather than having lots of glycogen?)

Answer 1

1. They contain lots of energy (more than glucose)
2. They form a dense energy store (any time glucose is turned into glycogen, it attracts twice the mass of water attached to it because of the OH groups). Fatty acids are hydrophobic so no wasted space with water molecules. Therefore higher energy per gram.

Question 2

What are fatty acids stored in teh adipose tissue as?

Answer 2

Triglycerides (aka triacylglycerols)

Question 3

How do u release energy from the adipose tissue store (lypolysis)?

Answer 3

3 Lipases break down the triglycerides into 3 fatty acids and glycerol.

These move into the blood. The fatty acids are too insoluble so they are carried by human serum albumin (HSA).

Fatty acids are released from HSA and travel to the outer membrane of a mitochondrion where they are activated

FA +ccoenzyme A -> Acyl CoA

Question 4

What is Beta Oxidation?

Answer 4

Break down of fatty acids to turn them into acetylCoA molecules

Question 5

What happens to excess fatty acids in the body?

Answer 5

Get turned into ketone bodies by the liver

Question 6

What are ketone bodies?

Answer 6

Fragments of fatty acids that are released into the blood to be used as fuel (particularly by the heart).

They are small and soluble

Question 7

Why are ketone bodies useful?

Answer 7

They require little conversion to entire the TCA cycle.

Whereas Glucose needs glycolysis and fatty acids need Beta Oxidation.

Question 8

Ketogenesis

Answer 8

Creation of ketone bodies.

1. 2 Acetyl-CoA’s joined together (reversal of last step of B-oxidation) to make a 4 carbon unit.
2. Then add another acetyl-CoA on the end.
3. The orginal acetyl-coA that was added is now cleaved off to do this cycle again.
4. Acetoacetate (the product made after acetyl-coA leaves) is released into the blood. It’s highly soluble.

OR
It’s first converted to
D-B-hydroxybutyrate or Acetone (don’t want to make acetone bc lose energy that couldve gotten bc CO2 comes off and also acetone is toxic)

ACETOACETATE and D-B-Hydroxybutyrate export ketone bodies to blood
DIAGRAM IN ON

Question 9

What is a symptom of people with diabetes doing ketogenesis?

Answer 9

Acetone in the breath, their breath smells like pear-drop sweets

Question 10

What does a high amount of acetone suggest?

Answer 10

Type 1 diabetes

Question 11

How are the ketone bodies used for energy?

Answer 11

D-B-Hydroxybutyrate is converted into acetoacetate via its dehydrogenase. This converts NAD+ to NADH + H+

Acetoacetate is reacted with succinyl-CoA which makes Acetoacetyl-CoA to regenerate the fatty acid.

Question 12

Liver cells can use its own ketone bodies, true or false?

Answer 12

False as they don’t express a certain enzyme to use it.

Question 13

What is NADPH associated with in pathways?

Answer 13

Synthetic pathways

Question 14

What are FAD and NAD+ associated with in pathways?

Answer 14

Breakdown pathways

Question 15

What are the main differences between fatty acid synthesis versus catabolism

Answer 15

1. Use of NADPH/NADP+ rather than NAD+/NADH

Not joining acetyl-CoA’s together, use of malonyl coA as a basic unit.

Question 16

Acetyl CoA + ATP + HCO3- = ….? in fatty acid anablism using acetyl CoA carboxylase

Answer 16

Malonyl CoA + ADP + Pi + H+

Question 17

What’s the first step in fatty acid synthesis?

Answer 17

Acetyl CoA carboxylase - irreversible. Stimulated by citrate and insulin. Inhibited by Palmitic acid and glucagon and adrenaline

Question 18

What is Acetyl CoA carboxylase inhibited by?

Answer 18

Palmitic acid and glucagon and adrenaline

Question 18

What is Acetyl CoA carboxylase stimulated by?

Answer 18

Insulin and citrate

Question 19

What does fatty acid synthase do?

Answer 19

Grows the chain 2 carbons at a time

Question 20

Is Acetyl coA made in the Matrix or Cytoplasm in the mitochondria?

Answer 20

Matrix

Question 21

How do u get Acetyl CoA out of the matrix to react with fatty acid synthase and Acetyl CoA carboxylase? (diagram in ON)

Answer 21

1. Acetyl CoA + OAA (oxaloacetate) = Citrate
2. Citrate transports to the cytoplasm through the IMM because there’s a citrate transporter
3. In the cytoplasm, it’s converted back into Acetyl coA (uses up ATP) which is then available to turn into malonyl coA.
4. OAA is converted into malate (USES NADH)
5. Malate converted into pyruvate (CONVERTS NADP+ TO NADPH WHICH IS REQUIRED FOR FATTY ACID SYNTHASE WITH MALONYL COA)
6. Pyruvate enters matrix to react with CO2 to make OAA (uses ATP)

Doesn’t matter about ATP’s used up in this process because there’s so much energy that ure trying to store as fatty acids anyways.

Question 22

Facts about Fatty acid synthase

Answer 22

240kDa = big protein

Six active sites

They have an acyl carrier protein which has an extendable arm which isn’t protein (a derivative of vitamin b5) which is used to transfer substrates from active sites to other active sites

Question 23

Step 1 in fatty acid synthesis

Answer 23

Acetyl-KS + Malonyl-ACP > Acetoacetyl-ACP + co2

Release of CO2 drives the reaction

Question 24

What does thioesterase do?

Answer 24

Uses water to break the bonds between sulfur and fatty acid

Question 25

What are lipoproteins?

Answer 25

A shell of phospholipids with cholesterol and proteins.
Inside is where all the energy molecules are (triglycerides and cholesteryl ester)

Question 26

What are the 5 types of lipoproteins? DIAGRAM IN ON

Answer 26

Chylomicrons - taking things from the gut and transporting them to adipose tissue and liver - in blood for 5 mins before they have lost all triglycerides and are taken into liver

VLDL - very low density lipoprotein - minutes to hours

IDL - Intermediate density lipoprotein - minutes to hours

LDL - Low - people refer to as “bad cholesterol” because it has dominant cholesterol within it but that’s a poor way of looking at it as it’s just a carrier in the same way the others are but just depleted of triglycerides - 3 days so it has time to become damaged, damaged LDL is the one that ends up in the walls of the arteries (so the saying shouldn’t be anything to do with cholesterol, it’s the lipoprotein carrying it.)

HDL - High - produced in different part of the body with a different function. Completely independent - 3-6 days - isn’t as prone to damage as the LDL

One turns into another and then the other turns into the other as they offload their cargo. They are different stages

BUT low density doesn’t turn into high density

Question 27

What happens to LDL if u smoke?

Answer 27

Take free radicles which attack the LDL’s travelling in the blood, damaging the protein part of it which causes it to lodge in the arteries.

Question 28

What is Familial hypercholesterolaemia (defect in LDL-R gene)

Answer 28

Too much cholesterol in blood

Defect in receptor that LDL should bind to. (should be that LDL bind to receptor and then taken into cell to be broken down). If there is a defect in receptor then LDL is left in blood forever.

If there’s a heterozygous mutation then half as many receptors so double normal plasma level of LDL (2500-5000mg/L) - consequence: coronary atherosclerosis, 1 in 2 chance of myocardial infarction (heart attack) by age 50

If homozygous , then no LDL-R at all so plasma LDL very high, (>6g/L), very high chance of death before age of 20.