Fat metabolism Flashcards
Do lipids provide a long term energy store or short term energy store
Long term energy store
why is triglycerides the ideal form of energy
- high energy density
- has a limitless capacity for storage
what is the main storage tissue for triglycerides
fat droplets
what does lipolysis do
- breaks down triglycerides into fatty acids and glycerol
what can fatty acids be used for
- they can be oxidised for energy - this happens in oxidative tissues such as muscle and liver
- or they can be converted to ketone bodies and used in non-oxidative tissues
what can glycerol be used for
glucose synthesis
what are the sites of lipogenesis
Liver
White adipose tissue
Lactating mammary gland
how are fatty acids stored
- they are stored in adipose tissue as triglycerides
what are the two stages of lipogenesis
- Formation of malonyl-CoA from acetyl-CoA
2. Elongation of the chain via fatty acid synthetase
what is lipogenesis
this is the formation of lipid molecules
How does lipogenesis happen
- Glucose enters the cell and is converted to pyruvate via glycolysis
- the Pyruvate then enters the mitochondria and takes part in the krebs cycle.
- The citrate produced in the krebs cycle, leaves the mitochondria, and is converted to acetylCoA in the cytoplasm.
- This then is converted to malonylCoA
- then to palmitate, which is acted upon by fatty acid synthetase to produce fatty acids
- this can be used to extend fatty acid chains by 2 carbon units
what is palmitate
this is the first fatty acid produced during FA synthesis and is the precursor to longer fatty acid
How is lipogenesis controlled
- it is controlled by Acetyl-CoA carboxylase
- this catlayses the irreversible carboxylation of acetyl-CoA to produce Malonyl-CoA
- Malonyl-CoA inhibits the carnitine shuttle and therefore prevents beta oxidation and fatty acid oxidation
- Acetyl-CoA carboxylase is active when dephopshorylated
- AMPK is the main kinase regulator of Acetyl-CoA carboxylase and is able to phosphorylate the serine residues on it therefore it deactivates it
what enzyme controls Acetyl-CoA carboxylase
AMPK
how does AMPK control Acetyl-CoA carboxylase
- AMPK is the main kinase regulator of Acetyl-CoA carboxylase and is able to phosphorylate the serine residues on it therefore it deactivates it
what are the three ways in which Acetyl-CoA carboxylase (ACC) is controlled
- Polymerisation – by citrate (activation), this increases ACC activity
- This is inihibted by palmitoyl-CoA - Phosphorylation by AMP dependent kinase and PKA (inactivation)
- Genetic control (long term)
How do hormones control Acetyl-CoA carboxylaseACC
- Insulin stimulates ACC and thus stimulates fatty acid synthesis by dephophosphrylating it
- glucagon and adnrelaine dephosphorylate it thus inhibiting fatty acid synthesis
what is lipolysis
- breakdown of lipids
when is lipolysis required
Used to mobilise energy stores during exercise or fasting
what stimulates lipolysis
Glucagon
Adrenaline and noradrenaline
Growth hormone
Cortisol
How is lipolysis controlled
- it is controlled by the enzyme hormone sensitive lipase (HSL)
- HSL is sensitive to the levels of cAMP which are regulated via hormonal levels
- cAMP is increased by glucagon and adrenaline
- cAMP is decreased by insulin
it is also controlled by ATGL - enzyme adipose triglyceride lipase
- this enzyme produces the diacylglycerol for the HSL to act upon therefore the HSL converts diacylglycerol to fatty acids and glycerol
what cells in the body metabolise fatty acids
- most living cells in the Body
- except red blood cells and neurones in the CNS can metabolise fatty acdsi
what are the 3 step process of the oxidation of fatty acids (overview)
- Once inside the cell, the fatty acid is activated by acetyl-coA
- This activated fatty acid is transported into the mitochondira via the carnitine shuttle
- Finally, ß-oxidation takes place
how does fatty acid activation happens
- this occurs in cytoplasm
- the fatty acid is converted to fatty acyl-CoA by the enzyme acyl-Coa synthetase
- This causes ATP to be converted to AMP
- this produces fatty acyl-CoA
How does the carnitine shuttle work
- the fatty acyl-CoA is converted to fatty acyl-carnitine by CPT-I enzyme which is located in the outer mitochondrial memrbane
0 it is moved into the intermemrbane space - the fatty acyl-carnitine is transferred into the mitochondrial matrix by a translocate enzyme
- this is then converted back to fatty acyl-CoA by CPT-II enzyme
- the free carnitine is shuttled back to the cytoplasm as the acyl-CoA is shuttled into the matrix of the mitochondria
what is the carnitine shuttle used for
it is used for acyl-CoA to enter the mitochondria
what is beta oxidation
this is the process by which the fatty acids are broken down
where does beta oxidation happen
- mitochondrial matrix
how does beta oxidation happen
- the long chains of fatty acids are broken down into 2 carbon units by acyl-CoA dehydrogenase
- this produces acetyl-CoA, NADH and FADH2
- the acetyl-CoA will enter the TCA cycle
- the NADH and FADH2 are coenzymes that will be used in the ETC to produce ATP
what are the products of beta oxidation
- this produces acetyl-CoA, NADH and FADH2
when will beta oxidation stop
-it will proceed until only 2 carbon units remain
how do you control fatty acid breakdown
- main point of control is transport via CPTI (once in the mitochondria there is little control)
- this is inhibited by malonyl-CoA this is produced when glucose is in high concentration which is involved in fatty acid synthesis
- it is stimulated by glucagon via cAMP
- carnitine shuttle is also controlled by transcription, levels rise in extended fasting and diabetes
where and what are ketone bodies produced from
- they are produced from acetyl-CoA this is only in the liver within the mitochondria
what are ketone bodies
They are soluble fuels, which can be used by tissues such as the brain, heart and muscle
what are examples of ketone bodies
Acetoacetate and beta-hydroxybutyrate
when does ketogensis take place
- takes place when blood glucose levels are low after glycogen stores have been used up
- for example in starvation
what activates ketogensis
excess acetyl-CoA in the liver
explain how excess acetyl-CoA in the liver causes the activation of ketosis
- in starvation oxaloacetate is used for gluconeogensis in the liver
- this means that there is not enough to take part in the TCA cycle
- this leaves excess acetyl-CoA which is then converted into ketones
how do you control ketogensis
HMG-CoA synthase
- this is activated in deactivated form
- gene expression increased by PPARa (this is a lipid regulated transcription factor)
- it is used in the conversion of acetyl-CoA to ketone bodies
what happens when ketone bodies reach the tissues
When ketones reach the tissues, they are reconverted back to acetyl-CoA, which can then enter the TCA cycle, followed by the ETC to produce ATP
- Most tissues in the body, have alternative fuel sources if glucose concentrations are low – such as fatty acids
- However, the brain requires glucose, so during starvation it will get a portion of its fuel requirements from ketone bodies
what can’t ketone bodies be used as fuel by the liver
Ketone bodies cannot be used as fuel by the liver, because the liver lacks the enzyme β-ketoacyl-CoA transferase, also called thiophorase.
what inhibits ketone body production
-insulin inhibits ketone body production
what happens to diabetic in relation to ketones
- uncontrolled diabetes means that there is a lack of insulin
- this can lead to excess ketone production and therefore cause diabetic Ketoacidosis
in beta oxidation what are the different forms of the enzymes
Different isoforms of enzymes with differing chain length preferences
where does beta oxidation occur
Occurs in most tissues that have mitochondria (except the brain) and therefore no beta oxidation occurs in red blood cells
what is metabolic flexibility
- this is the ability to switch between using glucose and lipids for energy production
what kind range of metabolic flexibility is in active individuals compared to sedentary people
• In skeletal muscle there is a smaller range of switching in sedentary people that more active individuals
how are fatty acids transported
- they are transported bound to albumin
- they are not water soluble
what are the 5 stages of glucose homeostasis
- Food goes in first using glucose coming in from food
- As this depletes start using glycogen
- As this depletes liver gluconeogenesis happens
- As this depletes there is an distinct drop of in gluconeogenesis
- Glucose is now being replaced by ketone bodies
