Energy Production: Lipds Flashcards

1
Q

What are some properties of lipids?

A
  • Structurally Diverse
  • Generally insoluble in water (hydrophobic)
  • Mostly only contain C, H, O (phospholipids contain P, N)
  • More reduced than carbohydrates as they release more energy when oxidised and complete oxidation requires more O2.
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2
Q

What are the classes of lipids?

A

Fatty acid derivatives which inc…
-Fatty acids -fuel molecules
-Triacylglycerols (triglycerides) -fuel storage and insulation
-Phospholipids -components of membranes and plasma lipoproteins
-Eicosanoids -local mediators
Hydroxy-methyl-glutaric acid derivatives (C6 compounds) which inc…
-Ketone bodies (C4) -water soluble fuel molecules
-Cholestrol (C27) -membranes and steroid hormone synthesis.
Vitamins… A D E K

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3
Q

What are the differences in energy storage between a 70kg and 135kg man?

A

When men are obese, energy is stored mostly as fat (so almost all the extra weight of the 135kg man will be fat).
It is a challenge to loose weight as fat has lots of energy!

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4
Q

What property of Triacylglycerols dictate how they are stored?

A

Triacacylglycerols are Hydrophobic. Therefore, they are stored in an anhydrous form in specialised adipose tissue. This storage and mobilisation is controlled by hormones.
Fat is only Utilised in prolonged exercise, in ‘starvation’ and during pregnancy.

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5
Q

Describe the extracellular digestion of fatty acids.

A

Pancreatic lipases hydrolyse lipids (TAG) inro fatty acids and glycerol in the small intestine.

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6
Q

What happens after pancreatic lipase have digested the fatty acids int the small intestine?

A

They fatty acids ate converted back into triglycerides in the GI tract.
They are then packaged into lipoprotein particles called
CHYLOMICRONS.

Next, they are released into circulation via lymphatics, carried to adipose tissue and stored as triglycerides.

They are then released as fatty acids when needed
and carried to tissues as albumin-fatty acid complex.

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7
Q

What are the properties of fatty acids?

A
  • Fatty acids can be saturated or unsaturated (one or more C=C).
  • They are also Amphipathic (they contain hydrophilic and hydrophobic groups)

Certain polyunsaturated Fatty Acids are essential because humans cannot introduce a double bond beyond C9. eg linolenic acid.

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8
Q

What happens in fatty acid catabolism?

A

Occurs in the mitochondria

  1. The Fatty Acid is activated (by linking to CoA outside the mitochondrion)
  2. Transported across the inner mitochondrial membrane using a carnitine shuttle
  3. The Fatty Acid cycles though a sequence of oxidative reactions with C2 removed with each cycle
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9
Q

What is fatty acid activation?

A

This occurs outside the mitochondria, in the cytoplasm.
-Fatty acids are activated by linking to coA via a high energy bond using fatty acyl CoA synthase as the enzyme.
Activated fatty acids do not readily cross the inner mitochondrial membrane.

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10
Q

What is a carnitine shuttle?

A

A Carnitine shuttle removes acyl group from CoA (using one of the cartinine acyltransferase enzymes)
and attaches it to carnitine to produce acylcarnitine. This then moves, via carnitine shuffle transporter, into the matrix.
It then occurs (kind of) in reverse so, acyl is removed from acyl cartinine and reattached to CoA. Then, the carnitine then travels through the carnitine shuttle transporter into the inter-membrane space.

This is regulated so, it controls the rate of fatty acid oxidation.

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11
Q

What can inhibit the carnitine shuttle? What does this lead to?

A

The carnitine shuttle is inhibited by malonyl-CoA (biosynthetic intermediate).
This Reduces the ability to metabolise fatty acids, so you get accumulation of fatty acid droplets in the cytoplasm.
This is especially prevalent in muscles which can lead to exercise intolerance.

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12
Q

What is the energy yield from a fatty acid, compared to that of glucose?

A

I stearic fatty acid (C18) produces 123 ATP whereas, glucose (C6) only produces 32 moles of ATP.
Even if the fatty acid was C6, it would still produce more (41) moles of ATP.

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13
Q

Where does B-oxidation occur?

A

B-oxidation occurs in most tissues including white blood cells. But, it does not work in the brain (because fatty acids cannot cross the blood-brain barrier or in red blood cells (as they don’t have mitochondria).

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14
Q

Summarise Fatty Acid metabolism

A

Fatty acid metabolism occurs in the mitochondria.

It is a cycle of reactions that removes 2C per cycle.

It is an oxidation reaction.

The H+ and e- are transferred to NAD+ and FAD so ATP can be during oxidative phosphorylation.

It stops in the absence of oxygen.

It does not actually synthesise ATP (this occurs in TCA and oxidative phosphorylation).

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15
Q

What is the first step in glycerol metabolism?

A

Activated - Glycerol forms glycerol phosphate using the enzyme glycerol kinase and energy from ATP.

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16
Q

Where is glycerol phosphate then used?

A

Either in glycolysis or in triacylglycerol synthesis

17
Q

What is the main convergence point for catabolic pathways?

A

Acetyl CoA is the main point of convergence.

18
Q

Functions of CoA

A

CoA is the most important intermediate in both catabolic and anabolic pathways.
it can form:
Fatty acids (inc triglycerols and phospholipids)
CO2
Hydroxymethyl glutamic acid (HMG) (inc. Ketone bodies and cholesterol which then forms steroid hormones)

19
Q

What are the three ketone bodies formed in the body?

A

Acetoacetate
Acetone
B-hydroxybytyrate.

20
Q

What is the normal concentration of ketones in the body? When does this change?

A
  • Normally, low conc of these (under 1mM)
  • Starvation (2-10mM) -Physiological ketosis
  • Untreated type 1 diabetes - Over 10mM (pathological ketosis)
21
Q

Where are ketone bodies synthesied synthesised?

A

Ketone bodies are synthesised in the liver.

22
Q

How is ketone body production controlled in the liver?

A

Produce NADH

When fatty acids are broken down, there is a high production of NADH.
This signals high energy, which inhibits the TCA.
So, citrate builds up meaning there is no Oxceloacetate.
This leads to a build up of CoA and so, metabolism is diverted to the ketone body pathways.

23
Q

What is ketone body production regulated by?

A

Insulin:Glucagon ratio.

24
Q

When high?

A

When the insulin/Glucagon ration is high (fed state) : Lyase is inhibited and reductase is activated so that cholesterol synthesis occurs.

THIS IS WHEN THERE IS MORE INSULIN

25
Q

When low?

A

When the insulin/glucagon ratio is low (starvation) lyase is activated, reductase inhibited. This begins ketone body synthesis.

THIS IS WHEN THERE IS MORE GLUCAGON

26
Q

What happens during starvation?

A

Break down muscle.
It is a progression of alteration within metabolism. The mechanisms ensure that there is always circulating glucose because the brain needs glucose to function.

27
Q

What are the properties of ketone bodies?

A
  • Water soluble molecules
  • Permits relatively high plasma conc.
  • Alternative substate
  • Above renal threshold (+10mM) then excreted in urine (ketourea)
  • Acetoacetate and b-hyroxybutyrate are relatively strong organic acids -Ketoacidosis
  • Volatine acetone may be excreted via the lungs
  • You may get the characteristic smell of acetone on breath.