Fatty acid metabolism Flashcards
1
Q
Lipid is a broad term and what does it encompass?
A
Fats, oils, waxes and other hydrophobic molecules such as cholesterol
2
Q
What are fatty foods rich in?
A
Triglycerides (TG)
3
Q
What makes something a fat or an oil?
A
Fats= solid at RT oils= liquid at RT
Both are triglycerides
4
Q
Whats another name for a triglyceride?
A
Triacylglycerols (TAG)
5
Q
Whats the structure of triglycerides?
A
Three fatty acids that are ester linked to glycerol backbone
6
Q
What makes something a fatty acid?
A
- long chain (12-24 C) hydrocarbons (acyls- long hydrocarbon chains)
- Methyl groups –>–>–> COOH group
- 0 or more double bonds
7
Q
What are the structure that can be made when a double bond is present?
How does this change a molecule?
A
- Cis or trans can change properties and therefore change what molecule it is
- Fatty acids can become more curled depending on how many double bonds are present (poly-cis)
8
Q
What are the different ways that fatty acids can be named?
Give an example for each using Oleic acid
A
- Common name: Oleic acid (oleate)
- Systematic name: cis-∆9 octadecenoic acid
- Omega or n system name: C18:1 (n-9)
9
Q
What can be a problem with systematic naming ?
A
They can start from different ends which may change the number carbon being referred to. E.g. systematic from COO- group whilst omega from CH3 group
10
Q
How does the omega series naming work?
use this example
A
- Lowest number defines series. So, if first double bond at position 3 and other beyond, it would be omega 3.
- C18:2 (n-6) means 18 carbon chain, has 2 double bonds, lowest one at position 6
11
Q
Humans have the ability to alter their fatty acids, what enzymes help with this and what is their role?
A
Elongases- increase chain length by 2 carbons
Desaturases- add double bonds
12
Q
When something is described as an essential Fatty acid (EFA) what does this mean?
A
Essential in biochemistry means that it is essential in the diet. But we as humans can’t make it so we have to eat it
13
Q
give examples of essential fatty acids
A
- Humans don’t have the right desaturase to add double bonds lower than omega 9
- Omega 3 or omega 6 FA therefore have to come from the diet and are termed essential
14
Q
Why would we need to alter fatty acids?
A
1. No need to for energy storage purposes
2. Membrane phospholipids
- Fatty acid length –> bilayer thickness
- Degree of unsaturation –> membrane fluidity
- Tissue-specific membrane composition e.g. brain is roughly 60% fat, enriched in omega 3 and 6
- Some FA are precursors to signalling molecules (e.g. prostaglandins, leukotrienes, thromboxane’s)
15
Q
How are fatty acids obtained from the diet?
A
16
Q
How are lipids in food digested?
A
- Majority of lipid in food is triglycerides
- Digested by pancreatic lipases
- Can now cross membrane into intestinal cells
17
Q
Tell me about the absorption/ assimilation of triglycerides?
A
18
Q
Tell me about the structure of a Lipoprotein?
What do they transport?
Give an examples of types of lipoproteins?
A
- A mixture of lipid and protein
- Phospholipid and cholesterol outer layer
- Triglyceride and cholesterol ester inner core
- Transport from gut to adipose tissues uses chylomicrons (up to 1 um in diameter)
- ApoB48, ApoC2 (important as binds to capillaries), ApoE
19
Q
How are fatty acids taken up into adipose tissue?
A
- Endothelial cells have lipoprotein lipase attached on the luminal side
- Lipoprotein lipase cleaves off fatty acids when enter cells
- When chylomicron has offloaded most of the TG it is called a remnant and is removed from circulation by the liver
20
Q
Tell me the stages to TG synthesis in adipose tissue of the liver (lipogenesis)
Name the enzymes and give the structures involved
A
This is different to intestinal synthesis
21
Q
Give a summary of fatty acid metabolism?
A
22
Q
What is the energy contained within a fatty acid?
A
- *Glucose** –> 17 KJ/g (4 kcal/g)
- *Fatty acid (palmitic)** –> 38 KJ/g (9 kcal/g)
23
Q
Whats an advantage of fatty acids?
A
They form dense energy stores
24
Q
Why are fatty acids used as opposed to glucose?
A
Glucose –> glycogen + 2x mass of water (H bond with water)- not efficient to store as a majority is water
Fatty acids –> triglycerides + no water (better as are hydrophobic so don’t store water, so all mass is energy molecules)
25
Tell me about Triglyceride hydrolysis for adipose tissue?
Tell me the enzymes used and their function
* Shrink and grow as TG are absorbed
* Every fatty droplet is surrounded by a shell of protein which restricts access to TG
* Only break down TG under certain conditions
* **Phosphorylase perilipin coat**
* **FA chains removed one at a time**
* **3 enzymes are above, have different substrates but same function**
26
What does free fatty acid bind to?
Human serum albumin (HSA)
27
What is TG broken down into and by what?
TG is broken down into 3x FA and by HSA
28
What are fatty acids picked up by and why?
Picked up by **major carrier proteins** **HSA**
As too hydrophobic to be transported in blood on its own (can pick up 3x FA and transport to rest of body)
29
Tell me about fatty acid entry into cells?
FA are released from HSA and travel to the outer membrane of a mitochondrion where they are activated
30
What are the two steps to fatty acid activation?
**FA + CoA --\> Acyl-CoA**
* ATP- consuming process catalysed by Acyl CoA synthetase
* conversion of AMP to ADP requires another ATP (-2 ATP overall before in mitochondria)
31
Tell me about Acyl-CoA entry into the mitochondria
* **Acyl- CoA** can cross outer mitochondrial membrane
* **CoA** must be swapped for **carnitine** to cross the inner mitochondrial membrane via a **carnitine acyltransferase enzyme**
* **Acyl- carnitine** is transported across the bilayer by a **translocase antiporter**
* Acyl chain is reattached to CoA once in the matrix
32
When a fatty acid is converted to acetyl CoA and enters the TCA cycle, what are the products of this reaction?
8 hydrogens
2 Carbon dioxides
33
In beta oxidation, what are Fatty acids (e.g. C16:0) catabolised into?
2C units
34
In beta oxidation, what bond is cleaved?
the beta carbon
35
What are the overall products of beta oxidation?
* **Acetyl CoA** (TCA cycle)
* **Acyl CoA** (14C) (round 2 of beta oxidation)
36
How many stages are there to beta oxidation?
What does each step release?
It is a four step process
each release 2C from FA
37
Tell me what happens in the first stage of beta oxidation, what type of reaction is it?
* enzyme used
* whats converted
* whats produced and from what
This is the oxidation of an alpha and beta carbon
38
Tell me about the second stage of beta oxidation?
* type of reaction carried out
* enzyme used
* whats produced
A hydration reaction
39
Tell me about the third stage of beta oxidation?
* type of reaction carried out
* enzyme used
* whats produced
The oxidation of beta carbon
40
Tell me about the fourth stage of beta oxidation?
* type of reaction carried out
* enzyme used
* whats produced
A thiolysis reaction
41
How long does the beta oxidation reaction go on for?
steps 1-4 repeat unit FA is completely removed
42
What does each cycle of the beta oxidation reaction produce?
1 x acetyl CoA
1x FADH2
1x NADH
43
Tell me about the equation for the #cycles required of the beta oxidation reaction ?
**#cycles= (#carbons/2)-1**
e.g.
= (C16/2) – 1
= 7 cycles for palmitic acid
44
In the final cleavage of the beta oxidation reaction what is produced?
The final cleavage yields **2 x acetyl CoA**
45
Tell me how much ATP is produced from each by products of beta oxidation?
46
If there is a longer chain FA, how does this effect the beta oxidation reaction
Longer chain FA simply have more cycles
e.g. stearic acid (18C) --\> 8 cycles --\> 146 ATP
47
How is the beta oxidation reaction affected by PUFA (polyunsaturated fatty acids)?
PUFA need **additional isomerase enzymes** to **convert cis double bond to trans double bond**
Need trans to cut of acetyl CoA (another way to do step 1 of beta oxidation when already have an existing double bond)
48
When do ketone bodies levels rise?
**Under conditions of prolonged fasting/starvation** a high level of TG hydrolysis occurs, and FA levels rise (when ketone body levels rise)
49
When are ketone bodies made?
When Acetyl CoA builds up in the liver beyond the capacity of the TCA cycle to use it, ketone bodies are made
50
Tell me about the heart and ketone bodies?
These are released into the blood and used as fuel by other cells especially heart
**Heart doesn’t use glucose or fatty acids, it runs on ketone bodies**
They require little conversion to enter TCA cycle so are a rapid source of energy, which is what makes them really useful for the heart
51
Why are ketone bodies easy to transport in the blood?
They are small and soluble molecules
52
Where does **ketogenesis** occur?
in the liver
53
What occurs in ketogenesis?
* three acetyl CoAs are joined
54
Tell me the steps to ketogenesis?
The enzymes used?
The by products?
55
Name 2 ketone bodies which are used as fuels?
* Acetoacetate
* Beta-hydroxybutyrate
56
Where is acetone lost?
in breath/ sweat/ urine (energy lost)
Can give an indication of type 1 diabetes
57
In destination tissue, Acetoacetyl-CoA is recreated, then split into what?
2 x acetyl CoAs
58
Why can't the liver use its own ketone bodies?
liver can’t use its own ketone bodies as it doesn’t express the enzyme **beta-Ketoacyl-CoA transferase**
59
Tell me how Acetoacetyl-CoA is produced from beta-hydroxybutyrate?
60
The following shows fatty acid degradation and fatty acid synthesis
61
Whats the start and end point of fatty acid anabolism?
Starting point is acetyl CoA (2C)
Endpoint is palmitic acid (16C)
62
How does fatty acid anabolism compare to beta oxidation?
How are they similar/ different?
Process is almost reverse of beta oxidation i.e. reduction
* **Use of NADPH/ NADP+** rather than NAD+/ NADH
* * **Use of Malonyl CoA** as basic unit- not acetyl CoA (doesn’t provide enough free energy for this reaction)
63
What enzyme is used to convert acetyl CoA --\> Malonyl CoA
Acetyl CoA carboxylase
64
Tell me about the enzyme **Acetyl CoA carboxylase?**
* What stimulates it?
* What inhibits it?
* Why its a heavy regulated enzyme?
**Stimulates**
* citrate
* insulin
**Inhibits**
* Palmitic acid
* Glucagon
* Adrenaline
**Heavy regulated enzyme**
* Only activate the enzyme when there is an excess of energy and want to make FA
* controlled by metabolites
* Can't use Malonyl CoA for anything else
65
Tell me fatty acid synthases role in FA elongation
* CO2 is released (the 1C)
* FAS binds to an acetyl CoA and releases a 3C chain which binds to the chain bit always lose 1C (in form CO2) so only adding a total of 2 overall
66
What are FAS and acetyl CoA carboxylase\>
cytoplasmic
67
Where is Acetyl CoA made?
In the matrix of mitochondria
68
Tell me about Acetyl CoA is converted to pyruvate and the whole loop of it all?
* include enzymes
* by products
* where each part occurs
The loop continues as long as you have acetyl CoA
69
How big is FAS?
272 KDa
multidomain enzyme
has 6 active sites and 6 enzymes
70
What are the enzymes included in FAS?
Tell me about ACP and its role
ACP is not an enzyme but is involved in enzymatic processes due to the thiol group
Job is to transfer substrates between different active sites
71
Tell me what enzymes of the FAS are involved in
1. modifying function
2. condensing functions
72
How many steps are there to fatty acid anabolism?
4
73
What enzymes of the FAS are involved in each step of fatty acid anabolism?
74
What are the stages in the first step of fatty acid anabolism?
What drives the reaction?
Write an overall equation for the reaction and the number of C involved?
* Acetyl group transferred to KS via ACP and MAT
KS= beta ketoacyl-ACP synthase
MAT= Malonyl/acetyl CoA-ACP Transacylase
* Malonyl transferred onto ACP by MAT
* KS joins the acetyl and malonyl (loss of CO2) – occurs inside active site of KS
75
Tell me what happens in step 2-4 of fatty acid anabolism?
What type of reaction occurs at each enzyme?
76
What is NADPH used for in fatty acid anabolism?
To reduce unwanted carbonyl group (on beta carbon)
* Butyryl ACP is a fatty acid when removed from ACP but want to make a long chain so requires elongation
77
Tell me what happens in fatty acid anabolism elongation?
* The 4C chain is transferred back to KS to start off step 1
* The cycle is repeated 6x until enough 2C have been added to make palmitic acid (16C), which is then released (thioesterase, breaks S-16C bond)
78
Tell me one instance when the fatty acid chain is cleaved slightly shorter?
Modifications to this: mammary tissue expresses a different thioesterase, which cleaves off shorter fatty acids to go into milk TG
79
Where are lipids transported from the liver to?
adipose tissue
80
in anabolic state, new FA will be converted to what?
TG and stored
81
If lipids are synthesised in the liver, what used to export TG to adipose and other tissues
lipoproteins
82
Tell me whats converted between the liver, gut and rest of thr body?
83
Tell me the structure of lipoproteins?
Whats attached to the outside?
84
Tell me the types of lipoproteins?
Their density and size compared to one another?
85
Tell me the lipoprotein composition?
How are the converted between each other?
Whats different about HDL?
* VLDL offloads TG into adipose tissue and turns into IDL
* Each one loses TG and shrinks to smaller size except LDL. HDL not made from LDL
* HDL made in tissue to go back to liver whereas other are made in liver to go to tissues
86
Tell me about lipoproteins life span?
**_Lipoprotein life span:_**
* **VLDL**= minutes --\> hours
* **IDL**= minutes --\> hours
* **LDL**= 3 days (damaged LDL before it ends up in arteries and clogs them, not amount of cholesterol they’re carrying)
* **HDL**= 3 --\> 6 days
* **Chylomicrons**= 5 minutes
87
The LDL-R gene can be defective
What happens in heteroxygous and homozygous cases?
Whats the main role when LDL is normal?
