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Gastrointestinal > Lipid Metabolism > Flashcards

Lipid Metabolism Flashcards

Biochemistry Lipid Metabolism and Ketones – Dr Stephen C Land Biochemistry Amino Acid Metabolism – Dr Stephen C Land (first half)

1
Q

What does increased fat intake without appropriate energy expenditure lead to?

A

increase in numbers of adipocytes
more fat in adipocytes
and obesity

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2
Q

What is fat needed for?

A
  • an energy source
  • for essential fatty acids (some polyunsaturates can’t be synthesized by the body & deficiencies can lead to membrane disorders, mitochondrial damage and increased skin permeability)
  • for fat-soluble vitamins (A, D, E, K, there absorption is closely linked to fat absorption and they are stored in body fat)
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3
Q

What are the 3 types of lipids?

A 
simple lipids (fatty acids, triglycerides, waxes)
compound lipids (phospho-, glyco-lipids, lipoprotein)
steroids (cholesterol, steroid hormones)
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4
Q

What are the characteristics of lipid molecules?

A

Predominantly hydrocarbon
Usually contain long chain fatty acids
Insoluble in water

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5
Q

What are triglycerides?

A

Triacylglycerols

  • they are the main storage form in adipose tissue
  • they are compact molecules and don’t require accompanying water storage
  • they are hydrophobic and have a high energy yield
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6
Q

What is the structure of a triglyceride?

A

glycerol and 3 fatty acids

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7
Q

What is a fatty acid?

A

they are mainly straight chains, aliphatic (no rings)
normally have an even no. of C atoms
double bonds usually cis configuration (H on the same side)

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8
Q

What are the 3 types of fatty acids?

A

saturated (no double bonds)
unsaturated (one double bond)
polyunsaturated (several double bonds)

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9
Q

How many carbons and double bonds does palmitic acid have?

A

16 carbons

0 double bonds

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10
Q

How many carbons and double bonds does stearic acid have?

A

18 carbons

0 double bonds

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11
Q

How many carbons and double bonds does oleic acid have?

A

18 carbons

1 double bond

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12
Q

How many carbons and double bonds does linoleic acid have?

A

18 carbons

2 double bonds

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13
Q

How do you name fatty acids?

A

C adjacent to carboxyl group is the alpha C
C furthest away is omega carbon
carboxyl group is numbered C-1

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14
Q

How do double bonds affect the melting points of fatty acids?

A

they lower the melting point

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15
Q

What are the main products of fat digestion?

A

glycerol - readily absorbed in the intestinal epithelial cells
fatty acids
monoglycerides

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16
Q

How are the products of fat digestion absorbed?

A

into the mucosal cells of intestine
the short - medium length fatty acids will enter the portal blood
longer chain FAs & monoglycerides are resynthesised to triglycerides, these triglycerides are then coated in a layer of protein, phospholipid and cholesterol to make chylomicrons

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17
Q

How do chylomicrons enter the bloodstream?

A

enter the lymph then enter the bloodstream

at muscle and adipose tissue, chylomicrons are attacked and cleaved by the lipoprotein lipases

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18
Q

What happens to free fatty acids at adipose tissue?

A

resynthesised into triacylglycerols for storage

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19
Q

What happens to free fatty acids in muscle?

A

oxidised to provide energy

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20
Q

What is lipolysis?

A

The breakdown of fat

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21
Q

What is the first step of the lipolysis of stored fat?

A

It is initially cleaved by hormone sensitive lipases
releases free fatty acids and glycerol
occurs when energy is needed

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22
Q

Name a rate limiting step in the conversion of fatty acids to ADP?

A

The carnitine shuttle

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23
Q

What step is needed before fatty acids can be oxidised to generate energy?

A

They must be converted to CoA derivatives which occurs in the cytoplasm and requires energy (2 ATP)
further oxidation of fatty acids occurs in the mitochondrial matrix - they are transported into the mitochondria through a special carrier mechanism

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24
Q

What happens to acyl-CoA (converted fatty acids) when they are left in the cytoplasm?

A

they are transferred from acyl-CoA to carnitine through the carnitine shuttle

25
Q

What is the carnitine shuttle?

A

an Acyl-carnitine transporter in inner membrane of the mitochondria which facilitates antiport of acyl-carnitine into the mitochondrion and carnitine out.
this results in acyl-CoA located in the mitochondrial matrix

26
Q

Where does beta oxidation occur?

A

in the mitochondrial matrix

27
Q

How many steps are there in a cycle of B oxidation?

A

4

28
Q

What are the products of a cycle of B oxidation?

A

1 acetyl-CoA
1 FADH2
1 NADH + H+
1 fatty acyl-CoA, shortened by 2 carbon atoms

29
Q

How many B oxidation cycles will a saturated fatty acid with an even number of C go through?

A

(the number of carbons/2) - 1

30
Q

What is the difference in yield of saturated fatty acids and unsaturated fatty acids?

A

unsaturated fatty acids are already partially oxidised and so yield less FADH2

31
Q

What is the difference in yield of even-chain fatty acids and odd-chain fatty acids?

A

odd-chain fatty acids yield propionyl-CoA in last step (3 carbon atoms) which is converted to succinyl-CoA and enters TCA cycle directly

32
Q

What is the difference in yield of unbranched-chain fatty acids and branched-chain fatty acids?

A

in branched chain fatty acids C-1 carbon oxidised to CO2 and acetyl- and propionyl-CoA released in equal numbers

33
Q

In glycerol breakdown what is the first step in the reaction?

A

Glycerol activation to glycerol-3-phosphate by glycerol kinase
present in liver and kidney but absent from adipose tissue, skeletal and heart muscle

34
Q

What intermediate of carbohydrate metabolism is gluycerol-3-phosphate dehydrogenated to?

A

dihydroxyacetone phosphate

35
Q

Where are ketone bodies formed?

A

liver mitochondria

36
Q

What are ketone bodies formed from?

A

acetyl-CoA which is produced in b oxidation

37
Q

What happens to ketone bodies once they have been formed in the liver?

A

they diffuse into the bloodstream and travel to the peripheral tissues and also play an important role in energy metabolism for heart muscle and renal cortex, (they are converted back to acetyl-CoA, which enters TCA cycle)

38
Q

What is the process fatty acid metabolism under normal conditions?

A

the oxidation of fatty acid yields acetyl-CoA
this acetyl Co-A enters citrate cycle if fat and carbohydrate degradation are balanced
acetyl-CoA depends on oxaloacetate (C4 compound) for formation of citrate (oxaloacetate can be provided as a side-product of glycolysis)

39
Q

What is the process of ketosis in starvation and diabetes?

A

the oxaloacetate is consumed for gluconeogenesis so fatty acids are oxidised to provide energy
acetyl-Co-A is therefore converted into ketone bodies, these are present in high levels in the blood
this will result in there being an excess of ketone bodies for extrahepatic tissue (e.g. heart, brain etc.)
ketone bodies are also moderate acids and so accumulation leads to severe acidosis (blood can’t buffer any more)

40
Q

What are the indications of ketosis?

A

impaired tissue function, particularly central nervous system
smell of acetone can be detected in breath

41
Q

What are the sites of de novo synthesis of fatty acids?

A 
liver
kidney
mammary glands
adipose tissue
brain
42
Q

When does lipogenesis take place?

A

when there is excess energy intake

43
Q

What happens when excess carbohydrate is taken in?

A

they are converted to fatty acids and triglycerides in the liver
free fatty acids are transported in plasma bound to albumin
triglycerides formed in the liver are transported to adipose tissue by VLDL for storage

44
Q

Where are fatty acids synthesized from acetyl-CoA?

A

in the cytoplasm of liver cells

45
Q

Where is acetyl-CoA generated from carbohydrate?

A

the mitochondria by pyruvate dehydrogenase complex, (Inner mitochondrial membrane is impermeable to acetyl-CoA so cittrate transports acetyl groups into the cytoplasm)

46
Q

How is citrate produced?

A

by condensation of acetyl-CoA with oxaloacetate (first step in TCA cycle)
when present at high concentrations, citrate is transported into the cytoplasm

47
Q

What is the direct precursor of fatty acids?

A

malonyl-CoA, it donated carbon atoms to new lipids

48
Q

What catalyses the conversion of acetyl-CoA to malonyl-CoA?

A

acetyl-CoA carboxylase which is expressed mainly in liver and adipose tissue

49
Q

What is fatty acid synthase?

A

a protein complex with 7 distinct enzyme activities, it can homodimerise through sulfhydryl cross bridges and it contains an acyl-carrier protein ACP

50
Q

What is the function of fatty acid synthase?

A

it catalyses synthesis of saturated long-chain fatty acids from malonyl-CoA, acetyl-CoA, and NADPH

51
Q

What are the 4 steps which fatty acid synthase catalyses fatty acid synthesis through?

A
  1. Condensation
  2. Reduction
  3. Dehydration
  4. Reduction and release
52
Q

What does happens in 1 cycle of lipogenesis by fatty acid synthase?

A

acetyl-CoA and malonyl-CoA as precursors, add 2 carbon atoms to the growing acyl chain which was derived from malonyl-CoA and is attached to ACP this addition requires NADPH as electron donor

53
Q

What length of carbon chain in a fatty acid cause it to be released by fatty acid synthase?

A

16 C

if the chain is to be elongated or unsaturated bonds are added further enzymes are requires

54
Q

What enzyme has an essential role in regulating fatty acid synthesis and degradation?

A

acetyl-CoA carboxylase

55
Q

What is the effect of insulin on the conversion of acetyl CoA to malonyl CoA?

A

it signals the fed state and stimulates storage of fuels and synthesis of proteins therefore it promotes acetyl-CoA carboxylase increasing conversion

56
Q

What is the effect of glucagon and epinephrine on the conversion of acetyl CoA to malonyl CoA?

A

glucagon is a hormone which signals the starved state and epinephrine is a hormone which signals requirement for energy so they inhibit acetyl-CoA carboxylase decreasing conversion

57
Q

What is the effect of citrate on the conversion of acetyl CoA to malonyl CoA?

A

citrate allosterically stimulates acetyl-CoA carboxylase increasing conversio. Citrate levels are high when acetyl-CoA and ATP are abundant

58
Q

What is the effect of palmitoyl-CoA on the conversion of acetyl CoA to malonyl CoA?

A

palmitoyl-CoA is abundant when fatty acids are in excess and so antagonises acetyl-CoA carboxylase decreasing conversion

59
Q

What is the process of triglyceride synthesis?

A

Requires glycerol-3-phosphate (G-3-P) which is produced in the liver from glycerol and in adipose tissue from glucose
(Adipose tissue production of triglycerides only during the fed state insulin stimulates adipose tissue uptake of glucose)
Triglyceride formation involves esterification

Gastrointestinal (12 decks)

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