Fatty Acid Production and Oxidation Flashcards
Name the 3 main sites of lipogenesis
Liver, white adipose tissue and lactating mammary glands
Name the type of transport shuttle that is involved in lipogenesis
Carnitine shuttle
Name the type of transport shuttle that is involved in lipolysis
Citrate shuttle
What is malonyl-CoA and how does it affect lipolysis?
malonyl-CoA is an intermediate in the mechanism of fatty acid synthesis (lipogenesis) and it works to inhibit the carnitine shuttle of lipolysis to prevent newly formed fatty acids from being oxidised in the mitochondriia
What is the role of acetyl CoA carboxylase in lipogenesis?
Conversion of acetyl CoA to malonyl CoA
Describe how acetyl CoA carboxylase can be modified by polymerisation
Enzyme is activated when in polymerised, and inactive when not. Citrate activates this enzyme by promoting polymerisation (as a lot of citrate indicates a lot of glucose which may need conversion to fatty acids). Conversely, the enzyme is inhibited by the final product of fatty acid synthesis (palmitoyl-CoA) which causes depolymerisation of filaments.
Describe how acetyl CoA carboxylase can be modified by hormone-dependent phosphorylation
Glucagon activates cAMP-dependent protein kinase which phosphorylates enzyme and inactivates it. Insulin promotes dephosphorylation to activate enzyme and lipid synthesis.
Name the three ways in which acetyl CoA carboxylase activity can be modified
polymerisation, phosphorylation and long-term genetic control
Why is lipolysis necessary?
Carbohydrate stores can only provide short-term energy buffering, and other sources required in long-term starvation (e.g. lipids and ketone bodies)
What is the initial substrate of lipolysis?
Triacylglycerol (TAG)
What are the two products of lipolysis?
Glycerol and 3 free fatty acids
Describe what happens to the free fatty acids formed from lipolysis
can be oxidised for energy (in muscle/liver - oxidative tissues) to form acetyl CoA (enters TCA cycle) in addition to many molecules of FADH2 and NADH which enter ETC. Fatty acids could also be converted to ketone bodies in liver for use in non-oxidative tissues (brain and erythrocytes)
Describe what happens to the glycerol formed in lipolysis
Can be use for glucose synthesis in liver or phosphorylated to form PEP to be used in glycolysis or gluconeogenesis
What is the role of the hormone-sensitive lipase in lipolysis?
Converts triacylglycerol into glycerol and 3 free fatty acids
Describe how the hormone-sensitive lipase enzyme is regulated
Sensitive to cAMP levels (which respond to hormone signals). Glucagon/adrenaline stimulates enzyme to encourage glycerol and FFA production. Insulin inhibits the enzyme in order to inhibit further production of glucose as it’s not required.
Describe the process of fatty acid activation in lipolysis
In liver/muscle cells: outer mitochondrial membrane facilitates free fatty acids to combine with CoA in presence of thiokinase to produce activated acyl CoA
Describe the carnitine shuttle in lipolysis
acyl CoA attaches to carnitine and loses CoA group in the presence of CPT-I. Fatty acyl-carnitine is formed and transported across membrane into mitochondrial matrix by translocase enzyme. Fatty acyl group transferred back to CoA (fatty acyl carnitine + CoA -> carnitine + fatty acyl CoA) using enzyme CPT-II. Carnitine is then returned to outer mitochondrial membrane to exchange for another molecule of fatty acyl-carnitine
What is meant by the ‘carnitine shuttle’?
CPT-I, CPT-II and translocase enzymes involved in the transport of acyl CoA into the mitochondrial matrix in fatty acid breakdown
What is malonyl-CoA?
Compound formed in fatty acid synthesis
Describe three ways in which the activity of the CPT-I enzyme (in the carnitine shuttle) can be modulated
Stimulated by glucagon (via cAMP), regulated transcriptionally with activity rising in extended fasting and diabetes (to increase fatty acid oxidation) and malonyl-CoA inhibits enzyme to prevent newly formed fatty acids from being oxidised immediately in the mitochondrial matrix
Which two types of cell cannot undergo beta-oxidation of fatty acids, and why?
Brain cells and erythrocytes as they do not have mitochondria
How to we obtain energy from fatty acids?
through beta oxidation; this involves oxidation by acetyl CoA dehydrogenases in the mitochondrial matrix
What are the products of beta oxidation of fatty acids?
NAD, FADH2 and acetyl-CoA. The first two will enter the ETC directly to release energy, whereas the acetyl CoA will enter the TCA cycle to release energy.
Define ‘ketogenesis’
The formation of ketone bodies from acetyl CoA (produced from the beta oxidation of fatty acids)
