Lipid Synthesis and Transport

As well as dietary lipid, we have an endogenous supply of triacylglycerol from the liver.

What does the liver synthesise TAG from?

Acetyl CoA cannot cross the mitochondrial membrane.

What molecule do we convert acetyl CoA into in order to allow it to cross the mitochondrial membrane?

Under the presence of what hormone will acetyl CoA and oxaloacetate combine in the mitochondrion to form citrate?

What happens to citrate in the liver cell once it has left the mitochondrion?

What does acetyl CoA react with to form malonyl CoA?

What enzyme catalyses the formation of malonyl CoA from acetyl CoA?

Which vitamin is acetyl CoA carboxylase dependent on for function?

What does malonyl CoA inhibit?

Malonyl CoA inhibits the enzyme [blank_start]acylcarnitine transferase[blank_end]. This means that [blank_start]fatty acids[blank_end] do not enter the [blank_start]mitochondria[blank_end] so they are not [blank_start]oxidised[blank_end].

How do we form the fatty acid chain?

What molecule provides the reducing power in fatty acid synthesis?

Fatty acid synthase has multiple active sites to carry out multiple reactions on one enzyme.

Fill in the blanks below to describe the sequence of reactions carried out by fatty acid synthase. 1. M[blank_start]alonyl CoA[blank_end] and A[blank_start]cetyl CoA[blank_end] combine in a condensation reaction. In this reaction, [blank_start]carbon dioxide[blank_end] is lost. 2. The molecule is [blank_start]reduced[blank_end], forming [blank_start]NADP+[blank_end] from [blank_start]NADPH[blank_end]. 3. The molecule is [blank_start]dehydrated[blank_end], releasing [blank_start]water[blank_end]. 4. The molecule is release again, forming [blank_start]NADP+[blank_end] from [blank_start]NADPH[blank_end]. 5. This cycle repeats where further [blank_start]malonyl CoA[blank_end] molecules are added to the acyl chain. In each reaction, [blank_start]3[blank_end] carbons are added but [blank_start]1[blank_end] is lost so there is a net increase of [blank_start]2[blank_end] carbons.

Fill in the blanks to describe how we determine the length of a fatty acid from synthesis. In the first condensation reaction between the first a[blank_start]cetyl CoA[blank_end] and m[blank_start]alonyl CoA[blank_end] molecules, the resulting molecule will have [blank_start]4[blank_end] carbons. This is because acetyl CoA has [blank_start]2[blank_end] carbons and malonyl CoA has [blank_start]3[blank_end] carbons, resulting in a [blank_start]5[blank_end]-carbon molecule, but a molecule of carbon dioxide is lost so the remaining intermediate has [blank_start]4[blank_end] carbons. Following this, a malonyl CoA molecule is added in every cycle. This adds [blank_start]3[blank_end] carbons but in each cycle [blank_start]1[blank_end] carbon is lost so there is a next increase of [blank_start]2[blank_end] carbons per cycle.

A fatty acid is synthesised from 6 cycles following the first condensation reaction of synthesis. How many carbons does it have?

Fill in the blanks to describe triacylglycerol synthesis. 1. Glycerol is activated by [blank_start]phosphorylation[blank_end] to form [blank_start]glycerol phosphate[blank_end]. 2. [blank_start]Fatty acids[blank_end] form [blank_start]ester bonds[blank_end] with glycerol. 3. Glycerol is [blank_start]dephosphorylated[blank_end].

This image shows a lipoprotein. Label it.

What is an apoprotein?

When an apoprotein forms a lipoprotein, which amino acids will be orientated on its outer surface?

Chylomicrons are a form of lipoprotein.

Which lipoprotein has the lowest density?

Which lipoprotein carries mainly endogenous triacylglycerols?

Which lipoprotein mainly carries cholesterol to the tissues?

Which lipoprotein carries cholesterol to the liver?

Which apoprotein do triacylglycerols, cholesterol and cholesterol esters associate with in the small intestine to form chylomicrons?

In circulation, which apoproteins do chylomicrons associate with? Check all that apply.

What is the source of the apoproteins that chylomicrons associate with in circulation?

Where is lipoprotein lipase found?

What hormone activates lipoprotein lipase?

Which molecule from chylomicrons activates lipoprotein lipase irrespective of insulin?

What happens to glycerol from chylomicrons after cleavage by lipoprotein lipase?

What enters the adipocytes when chylomicrons are cleaved by lipoprotein lipase?

Which apoprotein is NOT present on the chylomicron remnant left following the action of lipoprotein lipase?

The liver takes up chylomicron remnants. Which apoprotein is complementary to the liver receptors that facilitate this?

Fill in the blanks below to describe the transport of exogenous fat in chylomicrons. 1. The chylomicrons are assembled in the [blank_start]small intestine[blank_end]. Triacylglycerols, cholesterol and cholesterol esters are associated with [blank_start]apo B-48[blank_end]. 2. The chylomicron enters the circulation where it associates with [blank_start]apo E[blank_end] and apo [blank_start]C[blank_end]II, both of which are sourced from [blank_start]high density lipoprotein[blank_end]. 3. I[blank_start]nsulin[blank_end] and/or a[blank_start]po CII[blank_end] activate [blank_start]lipoprotein lipase[blank_end] found in the [blank_start]capillary[blank_end] endothelium. 4. [blank_start]Free fatty acids[blank_end] enter the adipose tissue for storage. 5. [blank_start]Glycerol[blank_end] is transported to the [blank_start]liver[blank_end] for gluconeogenesis. 6. The chylomicron remnant consists of triacylglycerols, cholesterol and cholesterol esters in association with apo B-48 and [blank_start]apo E[blank_end]. 7. [blank_start]Apo E[blank_end] receptors on the [blank_start]liver[blank_end] allow uptake of the chylomicron remnant.

Where is VLDL assembled?

Which apoprotein does VLDL have in association with its triacylglycerol, cholesterol ester and cholesterol?

VLDL associated with Apo CII and Apo E in the blood.

Where does VLDL source its apo E and apo CII from?

What is left after lipoprotein lipae in the capillaries cleaves VLDL?

How is low density lipoprotein formed from intermediate density lipoprotein?

Half of LDL is transported to the peripheral tissues and half of LDL is taken up by the liver.

Which apoprotein is complementary to receptors on the liver and peripheral tissues responsible for LDL uptake?

Fill in the blanks below to describe the transport of endogenous fat by VLDL. 1. VLDL is assembled in the [blank_start]liver[blank_end] in association with apo [blank_start]B-100[blank_end]. 2. In circulation, VLDL associated with Apo CII and Apo E sourced from [blank_start]HDL[blank_end]. 3. Apo CII and/or [blank_start]insulin[blank_end] activate [blank_start]lipoprotein lipase[blank_end] in the capillary [blank_start]endothelium[blank_end]. 4. [blank_start]Free fatty acids[blank_end] enter the adipose tissue and [blank_start]glycerol[blank_end] is transported to the liver for [blank_start]gluconeogenesis[blank_end]. 5. This leaves behind [blank_start]intermediate[blank_end] density lipoprotein. This returns its apo CII and apo E to [blank_start]HDL[blank_end]. 6. This leaves behind [blank_start]low[blank_end] density lipoprotein in association with [blank_start]Apo B-100[blank_end] only. 7. Half of LDL is transported to the peripheral tissues for uptake via the [blank_start]apo B-100[blank_end] receptors. The other half is transported to the [blank_start]liver[blank_end] for uptake via the [blank_start]apo B-100[blank_end] receptors.

Which apoprotein is HDL associated with?

HDL is synthesised in the liver and small intestine.

What happens to HDL in circulation?

What enzyme does Apo A1 activate?

What enzyme transfers fatty acids from lecithin (phosphatidylcholine) to cholesterol when cholesterol is taken up from the peripheral tissues?

What happens to cholesterol esters as they are synthesised in HDL?

What receptor picks up HDL on the liver?

Fill in the blanks below to describe the role of HDL in lipid transport. 1. HDL is synthesised in the liver and [blank_start]small intestine[blank_end] where it is associated with [blank_start]apo A1[blank_end]. 2. [blank_start]Apo A1[blank_end] activates the enzyme [blank_start]lecithin cholesterol acyl transferase[blank_end] (LCAT) which catalyses the transfer of [blank_start]fatty acids[blank_end] from [blank_start]lecithin[blank_end] to [blank_start]cholesterol[blank_end] from peripheral tissues to form [blank_start]cholesterol esters[blank_end]. 3. HDL begins as flat but becomes more spherical as it fills with [blank_start]cholesterol ester[blank_end] in circulation 4. [blank_start]Cholesterol esters[blank_end] are transferred to [blank_start]VLDL[blank_end]. This ensures that [blank_start]cholesterol[blank_end] can continuously be taken up from peripheral tissues. 5. HDL is taken up by the [blank_start]liver[blank_end] via the [blank_start]SR-B1[blank_end] receptor.

Fill in the blanks below to describe what happens when we consume cholesterol. 1. [blank_start]LDL[blank_end] binds to receptors on cell surface membrane. 2. [blank_start]LDL[blank_end] is taken into the cell by [blank_start]endocytosis[blank_end] whilst still complexed to its [blank_start]receptor[blank_end]. 3. The [blank_start]lysosome[blank_end] removes LDL from its receptor. 4. The [blank_start]receptors[blank_end] are recycled back to the membrane. 5. Cholsterol enters the [blank_start]nucleus[blank_end] and stimulates synthesis of [blank_start]enzymes[blank_end] that synthesise itself as well as the synthesis of [blank_start]receptors[blank_end].

What enzyme do we inhibit in order to reduce cholesterol synthesis?

Which of the following molecules inhibit cholesterol synthesis by inhibiting HMG-CoA reductase?

What results from LDL receptor deficiency?

Fill in the blanks below to describe the development of atherosclerosis. Atherosclerosis is the formation of fatty plaque blockages in the arteries. High [blank_start]LDL[blank_end] content can cause [blank_start]irritation[blank_end] of the arteries via the [blank_start]endothelial[blank_end] cells which begin to dysfunction. Their protective layer begins to break down which allows [blank_start]LDL[blank_end] through the layer. [blank_start]Macrophages[blank_end] respond to this by entering the arterial wall also in order to endocytose this [blank_start]LDL[blank_end]. This causes the [blank_start]macrophages[blank_end] to die and form [blank_start]foam[blank_end] cells. These [blank_start]foam[blank_end] cells accumulate to form a 'lake' of fat within the arterial wall known as a [blank_start]fatty streak[blank_end]. [blank_start]Smooth muscle[blank_end] cells migrate towards the [blank_start]fatty streak[blank_end] to form a [blank_start]fibrous cap[blank_end]. This [blank_start]reduces[blank_end] the diameter of the blood vessel.

Match the correct deficiencies from genetic disorders to their likely effects. [blank_start]Defective LDL receptor[blank_end] - hypercholesterolaemia, high plasma LDL [blank_start]Lipoprotein lipase deficiency[blank_end] - high chylomicrons, high VLDL [blank_start]Deficiency of apo CII[blank_end] - high chylomicrons, high VLDL Deficiency of [blank_start]apoproteins[blank_end] required for remanent uptake - high chylomicrons, high VLDL remnants