lipid synthesis and degradation

Question 1

what essential roles do fats play in the body?

Answer 1

→a role in membranes
→uptake of lipid soluble vitamins
→ as precursors of steroid hormones
→energy store

Question 2

what is the energy content of fat in comparison to proteins and carbohydrates?

Answer 2

→The energy content of fat per gram is over twice that of either carbohydrates or proteins, making an important energy source.

Question 3

when is the synthesis of fat triggered and what is the main source of it?

Answer 3

→when our caloric intake exceeds that of consumption, the excess is laid down as fat.

→Some tissues, such as cardiac muscle, use fats as their preferred energy source.

→dietary carbohydrate is the most common source, although amino acids can also be used.

Question 4

what is the structure of fatty acids?

Answer 4

→They are chains of methyl groups, with a terminal carboxyl group at one end.

→If double bonds are present, it is in a cis formation.

Question 5

why do humans have to obtain some fatty acids from diet?

Answer 5

→Humans are unable to make double bonds at positions less than position 9.
→That’s why there are ‘essential’ fatty acids that we have to obtain from our diets, as they cannot be made in our bodies.

Question 6

what makes up the majority of fatty acids made ?

Answer 6

→Palmitic acid (C16) makes up the majority of fatty acids made. If a different number of carbons is required, there are enzymes that will modify it.

Question 7

where does fatty acid synthesis take place and what does it require?

Answer 7

→ in the cytosol of hepatocytes
→Acetyl-CoA
→ NADPH
→ ATP It involves the sequential addition of 2 carbon units derived from Acetyl-CoA.

Question 8

how does the citrate-malate antiport system work and why do we need it?

Answer 8

→Pyruvate is transported from the cytosol to the inside of the mitochondrion.

→ it is converted to oxaloacetate, where Acetyl CoA is added to it to create citrate.

→ the citrate is brought out of the mitochondrion back into the cytosol, an acetyl CoA molecule is released from it, turning it back into oxaloacetate.

→Then, it is converted to malate (add NADP), followed by pyruvate once again (remove NADPH) (additional NADPH is provided by the pentose phosphate pathway).

→This is done to transport acetyl CoA outside of the mitochondrion as it can’t pass through the membrane.

Question 9

what is the first step of fatty acid synthesis?

Answer 9

→Acetyl-CoA + ATP + HCO3- ——-> Malonyl-CoA + ADP + Pi

→acetyl-CoA (2C) has a carbon molecule added to it by HCO3-, using ATP, changing it to Malonyl-CoA (3C).

→It is an important, irreversible, regulatory step activated by citrate (positive feedforward) and inhibited by palmitic acid (negative feedback).

→requires the vitamin Biotin (vitamin B7).

Question 10

what is the structure and function of cholesterol and how is it transported?

Answer 10

→rigid, hydrophobic molecule that is virtually insoluble in water.

→It is an important membrane component, and a precursor of sterols, steroids and bile salts.

→It is transported in the circulation as cholesteryl esters. It can’t be oxidised to O2 or H2O, so it provides no energy.

Question 11

what health issues can cholesterol imbalance cause?

Answer 11

→cholesterol imbalance can lead to significant health issues, such as gallstones and atherosclerosis.

Question 12

describe cholesterol synthesis

Answer 12

→Cholesterol is synthesised in the ER (with over 30 steps involved).

→ It starts with the activation of Acetate in Acetyl-CoA.

→The major regulatory step is the conversion of 3-hydroxyl-3-methyl-glutaryl CoA (HMG-CoA) to Mevalonate.

→Cholesterol inhibits HMG-CoA reductase, an enzyme involved in its own synthesis.

→difficult to remove circulating cholesterol by diet alone as endogenous synthesis is increased.

Question 13

what are the three steps of fatty acid degradation?

Answer 13

→MOBILIZATION
→ACTIVATION
→DEGRADATION

Question 14

what happens during fatty acid mobilization?

Answer 14

→A G-protein coupled receptor activates Adenylate Cyclase that increases the amount of cAMP made from ATP, which, in turn, activates Protein Kinase.

→This Protein Kinase activates Triacylglycerol Lipase.

→This converts Triacylglycerol to Diacylglycerol. The Diacylglycerol is then broken down into Glycerol and Fatty Acids.

Question 15

what happens to the glycerol mobilized in Fatty Acid Mobilisation?

Answer 15

→absorbed by the liver.

→1) Glycerol is phosphorylated to Glycerol-3-Phosphate.

→2) Glycerol-3-Phosphate is oxidised by Dihydroxyacetone Phosphate.

→3) Dihydroxyacetone Phosphate is isomerised to Glyceraldehyde-3-Phosphate (GAP).

→The majority of GAP goes towards GLUCONEOGENESIS, and a bit of it goes towards GLYCOLYSIS.

Question 16

what is fatty acid activation?

Answer 16

→fatty acids are transported to the liver and activated by Acyl-CoA Synthase in the cytoplasm.

→The Acyl-CoA produced is transported across the inner mitochondrial membrane bound to the alcohol Carnitine.

Question 17

how are fatty acids activated so they can cross the membrane?

Answer 17

→In the cytoplasm, the acyl-CoA will react with carnitine to give acyl-carnitine, which can then be transported across the membrane through the action of the enzyme Translocase.

→The acyl-carnitine is then broken down back into carnitine, releasing the Acyl to combine with the CoA, remaking acyl-CoA in the mitochondria.

→This allows the molecule to get across the membrane.

Question 18

what is fatty acid oxidation and where does it occur?

Answer 18

→It occurs in the mitochondria of the liver.

→Acyl-CoA is degraded by sequential removal of two carbon units

Question 19

what does fatty acid oxidation produce?

Answer 19

→This produces FADH2, NADH and Acetyl-CoA. The FADH2 and NADH form ATP.

→The Acetyl-CoA ( from β-oxidation) will enter the citric acid cycle, but only in the presence of glycolysis.

Question 20

why does fatty acid oxidation occur in the liver?

Answer 20

→In the liver, the main production of fatty acid oxidation is for generation of Acetyl-CoA which can be fed into citric acid cycle to generate energy,

→ACoA tends to be converted to ketone bodies.

Question 21

how many ATP molecules are produced from the oxidation of palmitate?

Answer 21

→106 ATP molecules.

Question 22

what are the steps in ketogenesis?

Answer 22

→Acetyl-CoA from breakdown of fatty acids is converted to Acetoacetyl-CoA

→ Acetoacetyl-CoA is converted to HMG-CoA

→HMG-CoA is converted to Acetoacetate Acetoacetate can be reduced to 3-β-Hydroxybutyrate or non-enzymatically to Acetone.

→These are the three ketone bodies and the two former ones are the important ones.

Question 23

what is the fate of ketone bodies?

Answer 23

→The acetoacetate is converted in the non-hepatic tissue back to Acetyl-CoA, this can then be used to generate ATP.

→Ketone bodies are a major energy source for cardiac muscle and renal cortex.

→During starvation or diabetes, 75% of the brains energy is derived from acetoacetate

→the production of ketones increases with decreased food intake.

Question 24

how does insulin regulate fat metabolism?

Answer 24

→increases glycolysis in the liver
→increases fatty acid synthesis in the liver
→ increases TG in adipose tissue
→ decreases β-oxidation

Question 25

how do glucagon and adrenaline regulate fat metabolism?

Answer 25

→increase TG mobilization

Question 26

How does Palmitate get generated from Fatty Acid Synthesis?

Answer 26

→Each cycle leads to the sequential addition of 2 carbons.

→So 6 cycles needed to generate 16C Palmitate Fatty Acid.

Question 27

How are the intermediates linked in Fatty Acid Synthesis?

Answer 27

→the intermediates in this reaction are covalently linked to ACP.

Question 28

How are the enzymes required for Fatty Acid Synthesis organised?

Answer 28

→All enzymes required form a multi-functional complex called Fatty Acid Synthase. This exists as a dimer.

Question 29

What is the importance of Carnitine?

Answer 29

→carnitine deficiency can cause muscle weakness or even death.
→as fatty acid degradation cannot occur without it.

Question 30

What inhibits fatty acid transport into the Inner Mitochondrial Matrix and how?

Answer 30

→The transport is also inhibited by malonyl-CoA, which is a step in the synthesis of fatty acids.

→ if it builds up, we will be moving towards synthesis, meaning this degradation transport process is inhibited.

Question 31

Why are FFA transported into the Inner Mitochondrial Matrix?

Answer 31

The enzymes that break down fatty acids are present in the Inner Mitochondrial Matrix.