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BIOSCI 106 > Section 4: Lipids > Flashcards

Section 4: Lipids Flashcards

1
Q

Lipids - amphipathic

A

Mostly hydrophobic (hydrocarbon), but with a polar or charged region (carboxylate)

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2
Q

Lipids - solubility

A

Usually not water soluble

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3
Q

What do lipids form

A

Don’t form large covalent polymers

Tend to form non-covalent higher-order structures

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4
Q

Lipids: Formation of non-covalent higher-order structures

A

Sequester the hydrophobic hydrocarbon component(s) from the (polar) aqueous environment
Stabilised by vdW interactions between hydrocarbon part

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5
Q

Fatty acids - strength

A

Weak acids - deprotonated at physiological pH (carboxylate form)

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6
Q

Fatty acids: Alkyl chains may be…

A

Saturated (fully reduced)
Unsaturated (some C=C):
- monounsaturated: one double bond
- polyunsaturated: many double bonds

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7
Q

Fatty acids are a type of _____

A

Lipid

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8
Q

Fatty acids: Saturated hydrocarbon chains

A

Can rotate freely about any C-C bond

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9
Q

Fatty acids: Unsaturated hydrocarbon chains

A

Can’t rotate around the double bond

Double bond is usually cis, which makes the hydrocarbon chain bend

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10
Q

Fatty acids: Number of carbons

A

Most naturally occurring fatty acids have an even no of C atoms because fatty acid synthesis involves adding 2C units

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11
Q

Fatty acids: Temperature and C

A

As no of Cs increase, melting point increases for both saturated and unsaturated

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12
Q

Fatty acids: Temperature and double bonds

A

Double bonds greatly reduce temp of melting point

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13
Q

Essential fatty acids

A

Required for good health and must be ingested, because mammals can’t introduce double bonds in fatty acids beyond carbon 9 and 10

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14
Q

Fatty acids: Major physiological roles

A
  1. Source of hormones and intracellular messengers
  2. Building blocks of micelles and membranes
  3. Post-translational modification of proteins
  4. Fuel
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15
Q

Fatty acids and lipids: Micelle

A

Fatty acids are wedge-shaped and tend to form spherical micelles
Polar head groups tend to be larger than their single hydrocarbon chain –> forms curved structure

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16
Q

Fatty acids and lipids: Micelles and phospholipids - number of tails

A

Micelle: one tail
Phospholipids: 2 tails

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17
Q

Fatty acids and lipids: Phospholipids

A

More cylindrical and pack tgt to form a bilayer structure

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18
Q

Biological membranes: Hydrophobic core - length

A

Hydrophobic core ~30Å

Hydrophobic core + interfacial on either side = ~60Å

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19
Q

Biological membranes: Interfacial region

A

Polar

Has some lipid headgroups, but also some water molecules - not a sharp boundary

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20
Q

Biological membranes: Lipid tails

A

Never perfectly straight

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21
Q

Biological membranes: Lipid tails - temp

A

Higher temp = more mobile

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22
Q

Biological membranes: How does the cell modify its curvature

A

By putting diff kinds of lipids in the membrane

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23
Q

What are found in biological membranes

A

Proteins, channels, sugars

Provide info to cell and ways to pass signals through the membrane

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24
Q

Lipid bilayers: States

A 
Gel state (below Tm)
Liquid crystal state (above Tm)
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25
Q

Lipid bilayers: Gel state

A

Lower temp and more saturated fatty acids

Hydrocarbon tails are packed tgt in a highly ordered gel state

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26
Q

Lipid bilayers: Liquid crystal state

A

Higher temp an d more unsaturated fatty acids

Movement of chains become more dynamic and interior of membrane resembles a liquid hydrocarbon

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27
Q

Fatty acids: Saturated vs unsaturated

A

Unsaturated fatty acids bent –> can’t pack as well tgt

  • fewer vdW can form
  • more dynamic / liquid-like
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28
Q

Major types of membrane lipids

A

Glycerophospholipids (glycerol backbone)
Sphingolipids (sphingosine backbone)
Sterols

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29
Q

Membrane lipids: Glycerophospholipids

A

Built on a glycerol backbone
Has a phosphate
2 fatty acid tails (any kind) added onto an O each

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30
Q

Membrane lipids: Sphingolipids

A

Already has a long hydrocarbon chain, so only one more fatty acid needs to be added, which is added onto a N
Head group attached to C1

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31
Q

Membrane lipids: Glycerophospholipid - basic structure

A 
Phosphate group
Glycerol backbone
R1 and R2 = fatty acids
R3 = head group
2 hydrophobic (fatty acid) chains point into membrane and phosphate group points in opp direction
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32
Q

Membrane lipids: Glycerophospholipids - phosphatidylserine (PS)

A

‘Eat me’ signal
Normally located in inner leaflet of PM
Moves to outer leaflet in apoptosis and attracts phagocytes to consume cell remnants

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33
Q

Membrane lipids: Cardiolipin (diphosphatidylglycerol)

A

4-tailed glycerophospholipid

Very large head group

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34
Q

Glycoglycerolipids are found where

A

Less common in animal membranes

Common in plant and bacterial membranes

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35
Q

Glycoglycerolipids - structure

A

Has a glycerol backbone

Carbohydrate/sugar attached via a glycosidic bond

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36
Q

Sphingolipids - where is it found

A

PM of all eukaryotic cells

Highest conc in CNS cells

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37
Q

Sphingolipids - function

A

Participate in cell signaling, e.g. regulating cell differentiation, proliferation, programmed cell death

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38
Q

Ceramides - basic structure

A

Also built on sphingosine backbone

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39
Q

Sphingolipid vs ceramide

A

In a ceramide, there isn’t really a head group attached to C1, just an OH that’s already attached
Whereas sphingolipid has a head group

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40
Q

Ganglioside - function

A

Sit in cell membrane and send out a signal which is recognised by other molecules that then lead to certain functions

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41
Q

Ganglioside - structure

A

Oligosaccharide linked to terminal hydroxyl group of a ceramide via a glucose molecule
Oligosaccharide chain contains at least an acidic sugar or sialic acid

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42
Q

Ganglioside - diarrhea

A

Ganglioside recognition and binding is the first step in the development of at least 2 diarrhea conditions

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43
Q

Ganglioside - immune system

A

Crucial for binding of immune system cells to sites of injury in the inflammation response

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44
Q

Gangliosides - Cholera

A

Pathological condition characterised by severe diarrhea

Cholera toxin recognises and binds to gangliosides (GM1) to gain access to inside of cell

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45
Q

Gangliosides - Enterotoxigenic E. coli

A

Most common cause of diarrhea

Like cholera, also produces a toxin that recognises and binds to gangliosides to gain access to cell

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46
Q

Cholera and diarrhea

A

Large V of water are normally secreted into small intestinal lumen, driven by Cl- secretion
Most of this water is absorbed before reaching the large intestine
Diarrhea occurs when secretion of water into intestinal lumen exceeds absorption

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47
Q

Cholera and diarrhea - steps

A 
Cholera toxins (and other bacterial toxins) bind to gangliosides and strongly activate adenylyl cyclase --> increase in intracellular conc of cAMP
Cl- channels open --> uncontrolled secretion of water (and Na+, K+, HCO3-) into intestinal lumen
Cholera toxin also affects enteric nervous system --> independent stimulus of secretion
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48
Q

Secretory diarrhea - fasting

A

Not resolved by fasting

Often lethal

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49
Q

Cholera toxin absorption stimulates / inhibits…

A

Stimulates cAMP production
Stimulates epithelial Cl- secretion

Inhibits Na+ absorption

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50
Q

Cholera - treatment

A

GM1-coated nanoparticles act as decoys to absorb cholera toxin before it binds to epithelial cells

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51
Q

Where is the highest conc of gangliosides found

A

In nervous system - 6% of lipids

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52
Q

Gangliosides - Tay-Sachs disease

A

Gangliosides in nervous system usually degraded in lysosomes by sequential removal of their terminal sugars
In Tay-Sachs disease, one removal enzyme is missing or deficient –> neurons become swollen with lipid-filled lysosomes

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53
Q

Gangliosides - Tay-Sachs disease - symptoms

A

Severe
Weakness and retarded psycho-motor skills before age 1
Demented and blind by age 2
Usually dead before age 3

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54
Q

Lipid composition

A

Varies between cell types and leaflets

Allows fine-tuning of membrane properties

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55
Q

Lipid membranes - asymmetric

A

Biological membranes are made of two layers / leaflets
Each leaflet faces a diff environment –> asymmetric
High conc of a lipid on one side = low conc of lipid on other side

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56
Q

Lipid membranes: Organelles vs cell membrane

A

Organelles:
Inner leaflet faces organelle interior
Outer leaflet faces cytoplasm

Cell membrane:
Inner leaflet faces cytoplasm
Outer leaflet faces environment

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57
Q

PM typically comprises __ diff lipid types

A

~60

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58
Q

Lipidation of proteins

A

Allows anchoring to membrane

Hydrophobic part slots into cell membrane

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59
Q

Type of lipid determines…

A

Protein location

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60
Q

Glycolipids are built on…

A

Either a glycerol backbone or sphingosine backbone

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61
Q

Fatty acids: How is fuel/fat stored

A

Stored as triacylglycerols

Excess from diet will also be stored here

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62
Q

Triacylglycerols AKA…

A

TAG
Neutral fats
Triglycerides

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63
Q

What are triacylglycerols formed from

A

Ester bonds between carboxyl groups of (same or diff) fatty acids (includes the C=O) and hydroxyl groups of glycerol

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64
Q

Fatty acids: Fuel - oxidation

A

Oxidation of fatty acids released from triacylglycerols produce energy for cellular process

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65
Q

Why are triacylglycerols/fats an efficient energy store

A

They are highly concentrated stores of metabolic energy;

  • highly reduced (lots of ability to be oxidised)
  • non-polar and so anhydrous

Can carry lots of energy into a small space and weight

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66
Q

Define anhydrous

A

Not much water

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67
Q

Fat yields ___x more energy than carbohydrates/proteins

A

~6.5x

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68
Q

What is the major energy storage form in most organisms

A

Fat

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69
Q

3 sources of fatty acids

A
  1. Digestion
  2. Adipose tissue
  3. Synthesis
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70
Q

Sources of fatty acids: Digestion - small intestine

A

Small intestine contains hydrolytic enzymes from pancreas which can be absorbed into the bloodstream

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71
Q

Sources of fatty acids: Digestion - chylomicrons

A

Transport triacylglycerols through lymph and bloodstream

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72
Q

What are bile salts

A

Emulsifiers

Amphipathic molecules synthesised from cholesterol in the liver and secreted from gall bladder

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73
Q

Transport of fatty acids and other lipids: Lipoprotein particles - function

A

Emulsify lipids for transport in the blood

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74
Q

Transport of fatty acids and other lipids: Lipoprotein particles - structure

A

Consists of a core of hydrophobic lipids (oil droplet) surrounded by a shell of more polar lipids and proteins

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75
Q

Transport of fatty acids and other lipids: Lipoprotein particles - apolipoproteins

A

Solubilise hydrophobic lipids
Contain cell-targeting signals; helps make sure the fats being transported end up in the right cell
Have a hydrophilic part that points outward

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76
Q

Lipoprotein particles - families

A 
Chylomicron
(Chylomicron remnant)
VLDL (very low-density lipoprotein)
IDL (intermediate density lipoprotein)
LDL (low-density lipoprotein)
HDL (high-density lipoprotein)
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77
Q

Lipoprotein density

A

Increases with increasing protein content (decreasing lipid content) because lipids are less dense than protein

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78
Q

Fats - solubility

A

Not soluble in water, therefore aren’t soluble in blood

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79
Q

How are fatty acids transported in blood

A

By lipoprotein particles

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80
Q

Density of water

A

Just under 1

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81
Q

Density of lipids vs water/protein

A

Lipids are generally less dense than protein and water

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82
Q

Lipids and proteins - density

A

More lipids = less dense

More proteins = more dense

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83
Q

Chylomicron remnants

A

What’s left over once the chylomicron has dropped off all its lipids

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84
Q

Lipoproteins: Chylomicron

A

Delivers dietary triacylglycerides to target tissues

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85
Q

Lipoproteins: Chylomicron remnant - function

A

Delivers dietary cholesterol esters left from chylomicron to liver

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86
Q

Lipoproteins: VLDL

A

Transports endogenous triacylglycerides from liver to periphery

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87
Q

Lipoproteins: IDL

A

Remnants of VLDL

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88
Q

Lipoproteins: LDL

A

Major transporter of cholesterol to periphery

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89
Q

Lipoproteins: HDL

A

Picks up cholesterol that’s no longer needed from circulation

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90
Q

Lipoproteins: Good vs bad cholesterol

A 
HDL = good cholesterol
LDL = bad cholesterol
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91
Q

Most lipids are ingested in the form of _____

A

Triacylglycerols, so must be degraded to fatty acids for absorption across the intestinal epithelium

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92
Q

How are triacylglyceroles in intestinal lumen solubilised

A

By bile salts

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93
Q

Digestion of dietary lipids - steps

A
  1. Cholic acid ionises to give its bile salt
  2. Hydrophobic surface of bile salt molecule associates with triacylglycerol, several of which aggregate to form a micelle
  3. Hydrophilic surface of bile salts face outward, allowing micelle to associate with pancreatic lipase/colipase
  4. Hydrolytic action of lipase frees fatty acids to associate in a much smaller micelle that is absorbed through the intestinal mucosa
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94
Q

What is cholic acid

A

A typical bile acid

COOH loses H to become COO- (ionised)

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95
Q

Triacylglycerides are hydrolysed by…

A

Pancreatic lipases

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96
Q

Digestion of dietary lipids: Pancreatic lipases

A

Secreted from pancreas
Catalyse hydrolysis of ester bonds between fatty acyl group and glycerol of triacylglycerols
- first hydrolyses off one of the outer fatty acids –> diacylglycerol
- then acts on other outer fatty acid –> monoacylglycerol

Releases 2 free fatty acids

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97
Q

Structure of bile salts

A

Triacylglycerols point in the same direction - this side is the hydrophilic face –> becomes the outer part of micelle
Other side is hydrophobic

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98
Q

Monoacylglycerol

A

Glycerol backbone with one acyl chain attached

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99
Q

Where do chylomicrons bind to membrane-bound lipases

A

At adipose and muscle cells

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100
Q

Fatty acids from adipose tissue: Stages of processing

A
  1. Mobilisation
  2. Activation and transport
  3. Degradation
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101
Q

Fatty acids from adipose tissue: Mobilisation

A

Triacylglycerols are degraded to free fatty acids and glycerol
hydrolysed by hormone-stimulated lipases in adipose tissue
Free fatty acids and glycerol are released from adipose tissue and transported to energy-requiring tissues

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102
Q

Fatty acids from adipose tissue: Mobilisation - enzymes

A

ATGL: adipose triglyceride lipase
triacylglycerol –> diacylglycerol

HSL: hormone-sensitive lipase
diacylglycerol –> monoacylglycerol

MGL: monoacylglycerol lipase
monoacylglycerol –> glycerol

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103
Q

Fatty acids from adipose tissue: Mobilisation - what can glycerol be used for

A

Glycolysis

Gluconeogenesis

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104
Q

Fatty acids from adipose tissue: Mobilisation - what happens to the free fatty acids produced

A

Transported into the blood plasma and undergoes fatty acid oxidation –> acetyl CoA –CAC–> CO2 + H2O

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105
Q

How are fatty acids transported

A

Since not soluble, they are transported bound to protein serum albumin

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106
Q

Serum albumin - function

A

Bind molecules that are insoluble in water and deliver them to tissues via blood, e.g.

  • fatty acids
  • hydrophobic hormones
  • drugs
  • metal ions
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107
Q

Uptake of fatty acids - passive?

A

Originally thought to occur largely by passive diffusion

Now thought to be mostly facilitated and regulated by proteins

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108
Q

Fatty acids from adipose tissue: Activation and transport

A

Fatty acids arrive in cytosol, but fatty acid degradation occurs in mitochondria so must be activated and transported

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109
Q

Fatty acids from adipose tissue: Activation and transport - steps

A
  1. Activation via adenylylation (requires ATP)
  2. Transfer to carnitine (replace CoA with carnitine molecule)
    Coenzyme A recycled and goes back to activate next fatty acid
  3. Transport through mitochondrial inner membrane
  4. Reconjugation with CoA
    Fatty acyl CoA goes to degradation pathway
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110
Q

Fatty acids from adipose tissue: Activation and transport - activated by?

A

Activated by formation of a thioester linkage to coenzyme A

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111
Q

Fatty acids from adipose tissue: Activation and transport - where does this take place

A

Outer mitochondrial membrane

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112
Q

Fatty acids from adipose tissue: Activation and transport - for fats to cross the membrane…

A

They must be conjugated to carnitine to enter the mitochondrial matrix

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113
Q

Fatty acids from adipose tissue: Activation and transport - carnitine acyltransferase I (CPT I)

A

Bound to outer mitochondrial membrane

Catalyses transfer of acyl group from coenzyme A to carnitine –> acyl carnitine

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114
Q

Fatty acids from adipose tissue: Activation and transport - translocase

A

Shuttles acyl carnitine across membrane

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115
Q

Fatty acids from adipose tissue: Activation and transport - carnitine acyltransferase II (CPT II)

A

Transfers acyl group back to coenzyme A

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116
Q

Is fatty acid degradation anabolic or catabolic

A

Catabolic - produces e- for oxidative phosphorylation

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117
Q

Is fatty acid synthesis anabolic or catabolic

A

Anabolic

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118
Q

What is fatty acid degradation

A

Degradation of a saturated acyl chain with an even no of C atoms attached to coenzyme A

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119
Q

Fatty acid degradation - double bonds / odd no of C atoms

A

Oxidation of an acyl chain containing double bonds or an odd no of C atoms requires additional steps

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120
Q

Fatty acid degradation: Pathway name

A

β-oxidation pathway

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121
Q

Fatty acid degradation: β-oxidation pathway - steps

A

Recurring sequence of 4 reactions:

  1. Oxidation of single bond to double bond. FAD –> FADH2
  2. Hydration - addition of water across double bond –> single bond. Forms an alcohol group
  3. Oxidation of alcohol to ketone. NAD+ –> NADH + H+
  4. Thiolysis - cleavage at β-C to release acetyl-CoA. Adds CoA to activate remainder of acyl chain for further rounds of β-oxidation
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122
Q

Fatty acid degradation: In each round of the β-oxidation pathway…

A

An acyl chain is shortened by 2Cs (in the form of acetyl-CoA)
Acetyl-CoA, NADH and FADH2 are generated

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123
Q

Fatty acid degradation: Where does the β-oxidation pathway occur

A

All reactions happen between α and β carbon of acyl-CoA molecule
α-C is next to carboxyl group, and next one is the β-C
Often the β-C is cleaved

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124
Q

Fatty acid degradation: β-oxidation pathway continues until…

A

There are no Cs left to remove

e.g. 7 rounds for C16

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125
Q

Fatty acid degradation: Fates of acetyl-CoA

A

Enters CAC or forms ketone bodies

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126
Q

Fatty acid degradation: Fates of acetyl-CoA - CAC

A

If fat and carbohydrate degradation are balanced, acetyl-CoA enters CAC

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127
Q

CAC: What does availability of oxaloacetate depend on

A

On the carbohydrate supply - formed from pyruvate

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128
Q

Fatty acid degradation: Fates of acetyl-CoA - Ketone bodies

A

When more fat than carbohydrate degradation (glycolysis)

Oxaloacetate is consumed to form glucose via gluconeogenesis

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129
Q

Examples of ketone bodies

A

Acetoacetate
β/D-3-hydroxybutyrate
Acetone

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130
Q

When are ketone bodies present in individuals

A

High levels of ketone bodies often present in blood of untreated diabetics
Also occurs when fasting or on low-carb diets

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131
Q

What are ketone bodies

A

Major fuel source for heart and kidney

Need to know what a ketone body looks like!

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132
Q

Which structures prefer ketone bodies

A

Heart muscle and renal cortex

Brain prefers glucose, but under prolonged starvation can adapt to get 75% of its energy from ketone bodies

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133
Q

Energy sources under starvation

A

After several days,

  • slight increase in fatty acids
  • decrease in glucose
  • large increase in ketone bodies in plasma
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134
Q

Palmitoyl-CoA (C16) needs _ rounds of β-oxidation

A

7

in 7th cycle, C4 is cleaved into 2 molecules of acetyl CoA

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135
Q

Fatty acid degradation - equation

A

Palmitoyl-CoA + 7FAD + 7NAD+ + 7CoA + 7H2O –>

8 acetyl-CoA + 7 FADH2 + 7NADH + 7H+

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136
Q

Molecules of ATP produced from fatty acid degradation

A

~2.5 ATP per NADH
~1.5 ATP per FADH2
~12 ATP per acetyl-CoA
~2 used to activate palmitate (-2)

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137
Q

Where does fatty acid synthesis occur

A

Cytoplasm

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138
Q

Fatty acid synthesis: What is acetyl-CoA formed from

A

From pyruvate in the mitochondria (glycolysis)

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139
Q

Mitochondria aren’t naturally permeable to…

A

Acetyl-CoA

So citrate carries acetyl groups through the inner mitochondrial membrane to cytoplasm for fatty acid synthesis

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140
Q

Fatty acid synthesis: Committed step

A

Starts with carboxylation of acetyl-CoA (2C) to form malonyl-CoA (3C)
Burns 1 ATP - irreversible
Catalysed by acetyl-CoA carboxylase

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141
Q

Fatty acid synthesis: Acetyl-CoA Carboxylase 1 and 2

A

Cytoplasmic enzymes

Regulates fatty acid synthesis and degradation

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142
Q

Fatty acid synthesis: -KS

A

Ketoacyl synthase

143
Q

Fatty acid synthesis: ACP - structure

A

Acyl carrier protein
A single polypeptide chain of 77 amino acids
Like a giant version of CoA

144
Q

Fatty acid synthesis: ACP - function

A

Used to carry around acyl chains

145
Q

ACP and coenzyme A - similarities

A

Both have a phosphopantethine group - long end of coenzyme A

Both end in a sulfur that can be joined onto molecules

146
Q

ACP and coenzyme A - differences

A

Coenzyme A:
Fatty acid degradation
Adenosine phosphate attached

ACP:
Fatty acid synthesis
Protein attached

147
Q

Synthesis pipeline: Fatty acid synthase (FAS)

A

Giant, multifunctional enzyme complex where all steps in fatty acid synthesis take place
One continuous polypeptide chain folded into domains
Contains enzymes for fatty acid synthesis
Acts as a dimer

148
Q

Synthesis pipeline: Where are fatty acid synthases found

A

In higher organisms only

149
Q

Fatty acid synthesis: Steps

A

Fatty acids are elongated by repetition:

  1. Condensation of malonyl-ACP and acetyl-KS
  2. Reduction of carboxyl group to OH (uses NADPH)
  3. Dehydration - forms double bond
  4. Reduction (uses NADPH) - double bond becomes single bond
  5. Translocation - shuffle growing chain onto KS protein –> ACP is free and cycle repeats
  6. C16-acyl-ACP is hydrolysed by a thioesterase (TE) to yield palmitate and ACP
150
Q

Fatty acid synthesis: When does it stop

A

Elongation cycle is repeated until C16-acyl-ACP is formed

151
Q

Fatty acid synthesis: Thioesterase (TE)

A

Acts as a ruler to determine fatty acid chain length

152
Q

Most commonly observed fatty acids - no of Cs

A

C16 and C18

153
Q

Bonds - fully reduced state

A

All single bonds

154
Q

Fatty acid synthesis: Condensation - cycles

A

Cycle 1: acetyl-KS + malonyl-ACP

Cycles 2-6: growing acyl chain-KS + malonyl-ACP

155
Q

To carry out fatty acid synthesis, you need…

A

2 molecules of NADPH

156
Q

Fatty acid synthesis: Where does NADPH come from

A

1 mole of NADPH per molecule of acetyl-CoA released from citrate
Additional NADPH required comes from pentose phosphate pathway

157
Q

The accumulation of precursors for fatty acid synthesis involve…

A

The coordinated use of multiple biochemical pathways

158
Q

Fatty acid synthesis - overall equation

A

8 acetyl-CoA + 7ATP + 14NADPH + 6H+ –>

Palmitate + 14NADP+ + 8CoA + 6H2O + 7ADP + 7Pi

159
Q

Major product of fatty acid synthase

A

Palmitate

160
Q

Elongation and unsaturation: ER

A

Chain lengthening

Introduction of double bonds into long-chain acyl-CoAs

161
Q

Longer fatty acids - eukaryotes

A

Formed by elongation reactions catalysed mainly by enzymes on the cytosolic face of the ER membrane

162
Q

Fatty acid degradation vs synthesis - location

A

Degradation - mitochondria

Synthesis - cytosol

163
Q

Fatty acid degradation vs synthesis - carrier of acyl chain

A

Degradation - coenzyme A
Synthesis - ACP

Both attach the acetyl to a sulfhydryl group

164
Q

Fatty acid degradation vs synthesis - adds/removes _____

A

Degradation - removes acetyl-CoA

Synthesis - adds malonyl-CoA

165
Q

Fatty acid degradation vs synthesis - oxidant/reductant

A

Degradation - oxidant is NAD+/FAD

Synthesis: reductant is NADPH

166
Q

Fatty acid degradation vs synthesis - starts from

A

Degradation - saturated fatty acid, any length

Synthesis - acetyl-CoA

167
Q

Fatty acid degradation vs synthesis - ends with

A

Degradation - acetyl-CoA

Synthesis - 16C saturated fatty acid

168
Q

Fatty acid degradation vs synthesis - processing pipeline

A

Degradation - no processing pipeline

Synthesis - FAS processing pipeline

169
Q

Fatty acid synthesis: ACC

A

Acetyl-CoA carboxylase

Helps regulate fatty acid synthesis

170
Q

Fatty acid synthesis AKA…

A

Fatty acid metabolism

171
Q

Fatty acid synthesis: Regulation of ACC

A

Subject to 2 types of allosteric regulation

Also regulated by a variety of hormones

172
Q

Fatty acid synthesis: ACC - allosteric regulation

A

Allosteric stimulation by citrate

Allosteric inhibition by palmitoyl-CoA

173
Q

Fatty acid synthesis: ACC - allosteric regulation by citrate

A

High citrate when both acetyl-CoA and ATP are abundant - signals raw material and energy are available for fatty acid synthesis
Leads to increased fatty acid synthesis

174
Q

Fatty acid synthesis: ACC - allosteric regulation by palmitoyl-CoA

A

Abundant when there’s an excess of fatty acids

Leads to decreased fatty acid synthesis

175
Q

Fatty acid synthesis: ACC - hormones

A

Inhibited by glucagon and epinephrine

Stimulated by insulin

176
Q

Fatty acid synthesis: ACC - glucagon and epinephrine

A

Stimulates its phosphorylation by AMP-activated protein –> inhibits ACC

177
Q

Fatty acid synthesis: ACC - insulin

A

Activates PDH phosphatase –> removes phosphate to activate PDH
Activates citrate lyase to create acetyl-CoA
Stimulates glucose uptake

178
Q

End product of fatty acid synthesis

A

Palmitoyl CoA

179
Q

Cholesterol - Janus-faced molecule

A

Described as a Janus-faced molecule because it has both hydrophobic and hydrophilic parts

180
Q

Cholesterol - solubility

A

Absolute insoluble in water - makes it useful in membranes but also potentially lethal if too much accumulates in one place

181
Q

Cholesterol - structure

A

Built on a saturated tetracyclic hydrocarbon

Fused cyclohexane rings all in chair conformation - makes it bulky and rigid compared with other types of lipids

182
Q

Cholesterol tends to _______ lipid membrane structure

A

Disrupt

183
Q

Cholesterol - amphipathic?

A

Weakly amphipathic

Very large hydrophobic part relative to hydrophilic part (polar bit = 1 OH)

184
Q

Roles of cholesterol: Membrane fluidity

A

Lowers the temp at which the membrane transitions from the gel to liquid crystal phase

185
Q

Roles of cholesterol: Lipid rafts

A

Cholesterol, sphingolipids and GPI-anchored proteins tend to associate in the membrane to form lipid rafts
Multiple lipid rafts can associate to form ‘platforms’ where certain proteins will preferentially interact - helps organise membranes

186
Q

GPI

A

Glycophosphatidylinositol

187
Q

Cholesterol derivatives - examples

A

Vitamin D
Bile salts
Steroid hormones

188
Q

Cholesterol derivatives: Vitamin D

A

Group of fat-soluble secosteroids

Most important forms in humans are vitamin D3 and D2

189
Q

Cholesterol derivatives: Vitamin D - function

A

Responsible for increasing intestinal absorption of calcium, magnesium and phosphate
Has many other biological effects

190
Q

Cholesterol derivatives: Vitamin D - source

A

Major natural source is synthesis of cholecalciferol in lower layers of skin epidermis, which is dependent on sun radiation
Only a few foods contain significant amounts of vitamin D

191
Q

Cholesterol derivatives: Vitamin D - not technically a vitamin?

A

Not essential as can be synthesised in adequate amounts by most mammals if exposed to sufficient sunlight, so not technically a vitamin

192
Q

Cholesterol derivatives: Vitamin D - activation

A

Activated by 2 hydroxylation steps, the first in the liver and the second in the kidney

193
Q

What are secosteroids

A

Steroids where part of the ring structure is broken open

194
Q

Cholesterol derivatives: Bile salts

A

Polar derivatives of cholesterol

Highly effect detergents

195
Q

Cholesterol derivatives: Steroid hormones

A

Precursor of potent signalling molecules, including the 5 major classes of steroid hormones
e.g. oestrogen, androgen, glucocorticoids, minerolocorticoids

196
Q

Cholesterol is essential for…

A

Animal life

197
Q

Cholesterol synthesis - de novo

A

Can be synthesised de novo (as new);

Principle sterol synthesised by all animals

198
Q

Cholesterol - plants and eukaryotes

A

Very little made by plants - make phytosterol instead

Absent in most prokaryotes

199
Q

Major site of cholesterol synthesis

A

In mammals, the liver (hepatic cells)

200
Q

Cholesterol synthesis: Where are the C atoms derived from

A

All 27 C atoms of cholesterol are derived from acetyl-CoA

Occurs in 3 stages

201
Q

Cholesterol synthesis: Stages

A
  1. Synthesis of isopentenyl pyrophosphate (cytoplasm)
  2. Condensation of 6 molecules of isopentenyl pyrophosphate to form squalene (ER)
  3. Cyclisation of squalene in an ‘astounding reaction’ and subsequent 18-step conversion of the tetracyclic product into cholesterol (ER)
202
Q

Cholesterol: Isopentenyl pyrophosphate (IPP)

A

An inactivated isoprene that is the key building block of cholesterol

203
Q

Cholesterol synthesis - committed step

A

Part of stage 1
Reduction of HMG-CoA to mevalonate
HMG-CoA reductase is an important control site in cholesterol biosynthesis

204
Q

Cholesterol synthesis: Stage 1 - regulation of HMG CoA reductase

A

Regulated by controlling:

  • rate of synthesis of reductase mRNA (activated by SREBP)
  • rate of translation of reductase mRNA
  • rate of degradation of reductase
  • phosphorylation of reductase (decreases activity)

Regulation at levels of transcription, translation and degradation can later the amount of enzyme in the cell more than 200x

205
Q

Cholesterol: SREBP

A

Sterol regulatory element-binding protein

Intracellular sensor that detects low cholesterol levels

206
Q

Cholesterol synthesis: Stage 1 - conversion of mevalonate to isopentenyl

A

3 consecutive reactions requiring ATP

207
Q

Cholesterol synthesis: Stage 1 - isopentenyl pyrophosphate and dimethylallyl pyrophosphate

A

Can readily interconvert

208
Q

Cholesterol synthesis: Stage 2

A

3 molecules of isopentenyl pyrophosphate condense to form farnesyl pyrophosphate
2 molecules of farnesyl pyrophosphate condense to form squalene

209
Q

Cholesterol synthesis: Stage 3

A

Squalene folds up from an open/linear structure into a ring-like structure
Squalene –> oxidosqualene –3 steps–> lanosterol –19 steps–> cholesterol

210
Q

Cholesterol: Heart disease

A

Fatty yellow-ish material on arterial walls of patients

211
Q

What is the essential control point of the cholesterol biosynthetic pathway

A

HMG-CoA reductase

212
Q

Cholesterol synthesis: Managing heart disease

A

Statin drugs use to treat heart disease target HMG-CoA reductase
Lovastatin and related compounds are potent competitive inhibitors (Ki = 1 nM) of HMG-CoA reductase

213
Q

Control of cholesterol uptake to manage heart disease: Loss of bile salts…

A

Reduces total cholesterol content body

214
Q

Control of cholesterol uptake to manage heart disease: Bile acid sequestrants

A

Binders that inhibit the intestinal reabsorption of bile salts
Orally administered +vely charged polymers
Bind -vely charged bile salts
Aren’t absorbed themselves

215
Q

Control of cholesterol uptake to manage heart disease: Statins

A

Resemble mevalonate - structurally and chemically similar

Mimic both the substrate and product of HMG-CoA reductase

216
Q

Cholesterol: Mevalonate in an enzyme

A

Folded up into a ring-like structure

217
Q

Cholesterol is carried by __________ as __________

A

Lipoprotein particles

Cholesterol esters

218
Q

Cholesterol metabolism: LDL

A

Cholesterol esters in LDLs are too hydrophobic to pass through the cell membrane, so the LDLs enter the cell through receptor-mediated endocytosis

219
Q

Cholesterol metabolism: LDL - what is engulfed

A

The entire LDL-receptor complex is engulfed and taken into the cell

220
Q

Cholesterol metabolism: LDL - steps

A

When LDL gets to cell, it’s recognised by LDL receptors in PM
Results in pips where LDL is coated with LDL receptor - the entire thing fuses around the LDL –> endocytic vesicle
Endocytic vesicle fuses with others –> endosome with multiple LDL particles in it - fuses with a lysosome –> lowers pH and breaks up the LDL particles
Releases amino acids, cholesterol, and cholesterol esters
After vesicle releases its contents, it goes back to the PM and waits for the next LDL to arrive

221
Q

What is familial hypercholesterolaemia (FH)

A

Absence or deficiency of functional receptors for LDL

222
Q

Familial hypercholesterolaemia (FH) - what happens

A

Cholesterol is deposited in various tissues because of the high conc of LDL cholesterol in the plasma

223
Q

Familial hypercholesterolaemia (FH): Homozygotes

A

Rare
No functional LDL receptors
Most die of severe coronary heart disease in childhood

224
Q

Familial hypercholesterolaemia (FH): Heterozygote

A

Common
~Half the normal number of LDL receptors
Pre-mature cardiovascular disease in 30s and 40s

225
Q

Familial hypercholesterolaemia (FH): Mutation

A

One class of mutations that results in FH generates receptors that are reluctant to give up the LDL cargo

226
Q

What is thermogenesis

A

Heat generation

227
Q

What is obesity

A

A medical condition where excess body fat (adipose tissue) has accumulated to an extent that it may have a -ve effect on health

228
Q

What does obesity increase the likelihood of

A 
Various diseases and conditions, particularly:
Cardiovascular diseases
Type 2 diabetes
Obstructive sleep apnea
Certain types of cancer
Osteoarthritis
Depression
229
Q

What is obesity caused by

A

Generally caused by a combination of excessive food intake, lack of physical activity and genetic susceptibility
Can also be caused by endocrine and mental disorders, or certain medications

230
Q

Obesity - BMI

A

Often defined as having a BMI > 30 kg/m^2
Intended for statistical measurement of pops; not a measure of individual body fat, build, or health
Only detects ~50% of cases of obesity

231
Q

Obesity ‘pandemic’

A

Most common nutritional disease in developed countries

Leading preventable cause of death worldwide

232
Q

Adipose tissue AKA…

A

Fat

Body fat

233
Q

Adipose tissue - structure

A

Loose CT composed mostly of adipocytes

234
Q

Adipose tissue - function

A

Main role is to store energy in the form of lipids

Also cushions and insulates the body

235
Q

Types of adipose tissue

A

White adipose tissue (WAT) - stores energy

Brown adipose tissue (BAT) - generates body heat

236
Q

Adipocytes AKA…

A

Lipocytes

Fat cells

237
Q

What are adipocytes

A

The primary constituent of adipose tissue

238
Q

Adipocytes are specialised in…

A

Storing energy as fat

239
Q

Types of adipocytes

A

White adipocytes - store energy as a single large lipid droplet and have important endocrine functions
Brown adipocytes - store energy in multiple small lipid droplets for use as fuel to generate body heat (thermogenesis)

240
Q

White vs brown adipocytes

A 
White adipocyte:
Found in obesity
Low mitochondria density
One large lipid droplet
Store energy
Endocrine functions
Brown adipocyte:
Anti-obesity
High mitochondria density
Numerous small lipid droplets
Produce heat and dissipate energy through thermogenesis
Endocrine functions
241
Q

How much does white adipose tissue contribute to body weight

A

In healthy, non-overweight humans, white adipose tissue comprises ~20% of body weight in men and ~25% in women

242
Q

White adipose tissue (WAT) - function

A

Energy storage
Acts as a thermal insulator - helps maintain body temp
Buffer impact
Structural roles

243
Q

Where is white adipose tissue found

A

Found all over the body

244
Q

White adipocytes - structure

A

Contain a single large fat droplet, which forces the nucleus to be squeezed into a thin rim at the periphery

245
Q

White adipocytes - contents

A

Have receptors for insulin, sex hormones, NE, glucocorticoids
Endrocinologically active

246
Q

Where is brown adipose tissue (BAT) found

A

Especially abundant in new-born humans and hibernating mammals
Also present and metabolically active in adult humans, but prevalence decreases with age
Mostly found around vasculature and organs, and shoulders and upper back

247
Q

Brown adipose tissue (BAT) - main function

A

Thermoregulation - generates heat by non-shivering thermogenesis

248
Q

Brown adipose tissue (BAT) - capillaries

A

Contains more capillaries that white fat, which supply the tissue with oxygen and nutrients, and remove/distribute the produced heat throughout the body

249
Q

Brown adipose tissue (BAT) - structure

A

Contain numerous small droplets of fat

Contain a much higher no of mitochondria

250
Q

What gives brown adipose tissue their colour

A

Their large no of (iron-containing) mitochondria

251
Q

Neonates

A

New-born humans

252
Q

Types of thermogenesis

A

Shivering thermogenesis

Non-shivering thermogenesis

253
Q

Shivering thermogenesis

A

Involuntary contraction of skeletal muscle

254
Q

Shivering thermogenesis - what does it occur in

A

All mammals exposed to cold will initially shiver to elevate heat production

255
Q

Shivering thermogenesis - hibernating animals

A

Process by which body temp of hibernating mammals is raised as they emerge from hibernation

256
Q

Shivering thermogenesis - oxygen consumption

A

In adult humans, it can reach intensities equivalent to 40% of maximum oxygen consumption

257
Q

What does shivering thermogenesis involve

A

Oxidation of mainly carbohydrates and lipids

258
Q

Shivering thermogenesis - how much can it increase heat production and core temp in humans

A

Can increase heat production by 3-4x and core temp by ~0.5°C in humans

259
Q

Shivering thermogenesis - efficiency

A

Inefficient method of heating

  • increases convective transfer of body heat away from core by increasing muscle blood flow
  • increases convective heat loss to the environment via gross bodily movement (wind chill)
260
Q

Shivering thermogenesis - spontaneity

A

When cold, it is spontaneous

261
Q

What is non-shivering thermogenesis

A

Heat production without shivering

262
Q

What is non-shivering thermogenesis carried out by

A

Brown adipose tissue (BAT)

263
Q

Discovery of non-shivering thermogenesis

A

Mice in cold (-10°C) food storage rooms

  • initially shivered constantly
  • later stopped shivering and appeared to thrive
  • found to have increased metabolic rate
264
Q

Non-shivering thermogenesis - BAT

A

Increase in blood flow to BAT in cold conditions

265
Q

Non-shivering thermogenesis - neonates

A

Brown fat plays an important role in helping neonates avoid hypothermia (a major death risk, especially when pre-mature)

266
Q

Why are infants more susceptible to cold than adults

A

Higher ratio of body SA to body volume
Higher proportional SA of the head
Little musculature and inability to shiver
Lack of thermal insulation
Inability to move away from cold areas and keep warm
Nervous system not fully developed - doesn’t respond quickly/properly to cold

267
Q

What is heat loss and heat production proportional to

A

Heat loss proportional to body SA

Heat production proportional to body V

268
Q

Brown adipose tissue (BAT) - neonates

A

Especially abundant in neonates, especially those born without fur, and hibernating animals

269
Q

How does non-shivering thermogenesis by BAT maintain body temp during cold exposure

A

Warms blood in surrounding blood vessels before its distribution to the periphery
Ensures an optimal temp for biochemical processes in adjacent organs

270
Q

Mechanism of non-shivering thermogenesis

A

Energy is instead released as heat by allowing protons to flow down their gradient without producing ATP (proton leak) - ATP synthase is blocked
Uses UCP1

271
Q

UCP1

A

Uncoupling protein 1
Allows protons to leak across the inner membrane of the mitochondria
Releases stored energy as heat

272
Q

Brown adipocytes - efficiency

A

Energy inefficient for ATP production

Energy efficient for heat production

273
Q

Endotherms

A

Organisms that generate their own heat

274
Q

What cells can uncouple proton transport from ATP production

A

All cells of endotherms

275
Q

How is BAT specialised for non-shivering thermogenesis

A

Each cell has more mitochondria than usual

These mitochondria have a higher-than-normal conc of UCP1 in the inner membrane

276
Q

Brown adipose tissue: NA

A

Noradrenaline

277
Q

Brown adipose tissue: SNS

A

Sympathetic nervous system

278
Q

Brown adipose tissue: β1,2,3

A

β-adrenoceptors
Sit in outer membrane of brown adipocytes
Brown adipocytes mainly have β3, other cells will have other β-adrenoceptors

279
Q

Brown adipose tissue: AC

A

Adenylyl cyclase

280
Q

Brown adipose tissue: PKA

A

Protein kianse A

281
Q

Brown adipose tissue: CREB

A

cAMP regulatory element binding protein

282
Q

Brown adipose tissue: UCP1

A

Uncoupling protein 1

283
Q

Brown adipose tissue: HSL

A

Hormone sensitive lipase

284
Q

Brown adipose tissue: TG

A

Triacylglycerol

285
Q

Brown adipose tissue: FA

A

Fatty acids

286
Q

Brown adipose tissue: CM

A

Chylomicrons

287
Q

Brown adipose tissue: LPL

A

Lipoprotein lipase

288
Q

Activation of brown adipose tissue - steps

A
  1. NA released by SNS acts on β-adrenoceptors, primarily β3
  2. This stimulates generation of cAMP by adenylyl cyclase, which activates PKA
  3. PKA catalyses phosphorylation of CREB –> increased ucp1 gene expression
  4. PKA also catalyses phosphorylation of HSL and perilipin –> activates HSL and dissociates perilipin from lipid droplets –> activates lipolysis of TG stores
  5. Released FA stimulate UCP1 and are channeled to the mitochodnria where they enter the β-oxidation pathway and CAC –> ETC –> proton gradient
  6. UCP1 dissipates the proton gradient generated by the respiratory chain –> release of energy as heat (thermogenesis)
289
Q

Adipocytes: Perilipin

A

The protein that covers the intracellular lipid droplets

290
Q

DNP - safety

A

Not safe - can be deadly

291
Q

DNP - what does it act as

A

Acts as a proton ionophore to shuttle H+ across cell membranes
Similar to UCP

292
Q

What are kinases

A

Proteins that phosphorylate other proteins

293
Q

DNP - steps

A

Dissipates the proton gradient across the mitochondrial membrane
Instead of producing ATP, the energy of the proton gradient is lost as heat

294
Q

More DNP –>

A

Less efficiency energy production –> metabolic rate increases (and more fat is burned) to compensate

295
Q

BAT: Humans - children

A

Presence of BAT in newborns and children is well established

296
Q

What was BAT believed to become? What was confirmed recently

A

Was believed to become more like white adipose tissue in adult humans, but presence and role in thermogenesis only recently confirmed

297
Q

BAT: Modern imaging technology

A

Detection of BAT was enabled by modern imaging tech:

  • PET - metabolic info
  • CT - structural info

Combing these overlays functional and anatomical data

298
Q

BAT: Modern imaging technology - PET

A

Positron emission tomography

Can identify diff types of metabolic activity

299
Q

BAT: Modern imaging technology - CT

A

Computed tomography

Structural info

300
Q

How are types of BAT categorised

A

Categorised based on cell morphology and location

301
Q

Both types of BAT have…

A

Small lipid droplets and numerous mitochondria

302
Q

Types of adult BAT

A

Classic or Constitutive

Beige or Brite (brown-in-white) or recruitable

303
Q

Adult BAT: Classic / Constitutive - where is it found

A

Found in highly vascularised deposits, typically between the shoulder blades, surrounding the kidneys, neck, and supraclavicular area, and along the spinal cord

304
Q

Adult BAT: Classic / Constitutive - lipid droplets

A

Smaller of the two types with numerous small lipid droplets

305
Q

Adult BAT: Beige / Brite / Recruitable - where is it found

A

Interspersed with white adipocytes in WAT

Develops from white adipocytes after stimulation by SNS (noradrenalin)

306
Q

Adult BAT: Beige / Brite / Recruitable - lipid droplets

A

Greater variability in lipid droplet size and a greater proportion of lipid droplets to mitochondria than BAT –> beige appearance

307
Q

Adult BAT: Beige / Brite / Recruitable - when is it found

A

Recruited when you need it to generate heat

308
Q

Adult BAT: Classic / Constitutive - when is it found

A

Always occurring

309
Q

Browning of WAT to form BAT - reversibility

A

Adaptive and reversible response to environmental challenges

310
Q

Adult BAT: Beige / Brite / Recruitable - what is it rich in

A

Rich in UCP1 and mitochondria

311
Q

What factors cause browning / whitening of adipocytes

A

White adipocytes –browning–> beige adipocytes:

  • cold
  • β3-agonism

Beige adipocytes –whitening–> white adipocytes:

  • thermoneutrality
  • high-fat diet (HFD)
312
Q

Almost everything used to combat obesity is ________

A

Reversible

313
Q

Browning of WAT: Evidence in rodents - newborn lacking BAT

A

Newborn (neonate) mice lacking BAT (knockout, K) have reduced body temp

314
Q

Browning of WAT: Evidence in rodents - adult mice lacking BAT

A

Have normal body temp at 22°C
Adult slowly to prolonged cold temp
Exhibit increased browning of some types of WAT for thermoregulation

315
Q

Is conversion of WAT to BAT in rodents a short or long term process

A

Allows mice to have normal body temp at colder temps over a longer time - longer term

316
Q

Browning of WAT: Evidence in rodents - UCP

A

Control mice with plenty of BAT don’t have any UCP in their WAT
Knockout mice have lots of UCP expressed in sWAT
Suggests WAT is being converted to BAT to generate heat

317
Q

What is sWAT

A

Subcutaneous white adipose tissue

318
Q

What does NA stimulate conversion of

A

WAT to BAT

319
Q

Browning of WAT: Evidence in rodents - NA (NE)

A

Knockout mice have higher levels of NA –> suggests it is needed to turn WAT into BAT

320
Q

Browning of WAT: Evidence in rodents - α-tubulin

A

A protein found in all cells

Control to make sure there’s some cellular protein loaded onto the gel

321
Q

Browning of WAT: Evidence in rodents - No BAT gives ____ skin temp, about ___ of normal

A

Reduced

94%

322
Q

Browning of WAT: Evidence in rodents - infrared image

A

Tells us how much heat was being given off the mice

323
Q

Browning of WAT in rodents by ‘hot’ and cold therapy - β-AR

A

Extensive efforts have been made to pharmacologically activate BAT thermogenesis using synthetic β-adrenergic receptor (β-AR) agonists

324
Q

Browning of WAT in rodents by ‘hot’ and cold therapy - examples

A

Chilli peppers (capsinoids, non-pungent capsaicin analogues) and mild cold exposure

325
Q

Browning of WAT in rodents by ‘hot’ and cold therapy - experiment

A

Mice were fed a high fat diet supplemented with capsaicin analogues under mild cold conditions for 8 weeks
This synergistically suppressed body weight gain and increased energy expenditure on a high-fat diet

326
Q

Browning of WAT in rodents by ‘hot’ and cold therapy - steps

A

Cold sensation registered on skin and transmitted to WAT deposits through SNS and β-AR
Capsinoids bind to capsinoid receptor in gut

327
Q

Browning of WAT in rodents by ‘hot’ and cold therapy - capsinoid receptor

A

Transmembrane receptor

Activation of it can produce a painful burning sensation

328
Q

Browning of WAT in rodents by ‘hot’ and cold therapy - BAT adipogenesis is synergistically stimulated through…

A

Increased β-AR expression

Stabilsiation of transcription factor PRDM16, a major transcriptional regulator of BAT development

329
Q

Cachexia - symptoms

A

Inflammation
Body weight loss
Atrophy of adipose tissue
Skeletal muscle wasting

330
Q

Where is cachexia observed

A

In a majority of cancer patients with advanced disease
Also at the end stage of various other morbidities, e.g. infectious diseases (AIDS) or chronic conditions (heart failure)

331
Q

Cachexia is responsible for ___ of total deaths from cancer

A

20%

332
Q

What does cachexia involve

A

Systemic inflammation and IL-6, both of which induce and sustain WAT browning

333
Q

Cachexia: IL-6

A

Stimulates the adrenal gland to reduce catecholeamines –> induces NA

334
Q

Cancer cachexia patients stain positive for…

A

UCP1 in WAT

335
Q

What seems like a promising approach to ameliorate cachexia in cancer patients

A

Inhibition of WAT browning, as it stops the the high energy expenditure

336
Q

Thermogenic capactiy

A

Ability of the body to produce heat

337
Q

WAT - burn trauma

A

Browning of WAT occurs in humans following burn trauma

338
Q

Browning of WAT in humans: Burn trauma - what is it

A

Severe and prolonged adrenergic stress

339
Q

Browning of WAT in humans: Burn trauma - what does it result in

A

Prolonged elevation of circulating NA levels for several weeks post-injury

340
Q

Browning of WAT in humans: Burn trauma - what does it increase

A

Resting energy expenditure
Expression of UCP1
No of mitochondria
Oxidative capacity

341
Q

Browning of WAT in humans: Burn trauma - what could it reflect

A

Need for increased thermogenesis to maintain normal body temp following loss of insulating skin barrier

342
Q

Browning of WAT in humans: Burn trauma - NA

A

Large 10x increase in circulating NA - persists for several weeks post-burn
Much greater than the transient increases (1.5x) in NA levels seen in patients exposed to chronic cold
This ‘catecholaminergic’ surge associated with larger burns may contribute to browning of WAT

343
Q

Artificially stimulating and controlling browning in humans - experiment

A

Healthy young male subjects:

  • some had BAT already (+), others didn’t (-)
  • BAT+ and BAT- subjects randomly assigned to 2 groups
  • one group exposed to cold at 19°C for 2 hours
  • other group at 27°C for 2 hours
344
Q

Artificially stimulating and controlling browning in humans - experiment results

A

Exposure to lower temp increased energy expenditure

Activation of pre-existing BAT but no browning of WAT - no new BAT

345
Q

Artificially stimulating and controlling browning in humans - cold vs capsinoid exposure

A

Prolonged cold exposure increases browning of WAT

Prolonged capsinoid treatment increases browning of WAT

346
Q

Artificially stimulating and controlling browning in humans: Cold vs capsinoid exposure - interpreting experiments

A

Must be careful interpreting these experiments because don’t know how much of these results is because of the experiment and how much is because of the diff people

347
Q

Artificially stimulating and controlling browning in humans: Bile acids

A 
Can activate TGR5 -->
Increases cAMP conc -->
Activates deiodinase enzyme D2 -->
Produces active thyroid hormone -->
Converts T4 into T3 -->
Increased UCP1 and BAT activity
348
Q

TGR5

A

A thyroid G-protein coupled receptor

349
Q

Artificially stimulating and controlling browning in humans: Bile acids - experiment

A

12 healthy females treated for 2 days

Orally took a bile acid (CDCA)

350
Q

Artificially stimulating and controlling browning in humans: Bile acids - experiment results

A

Small increase in whole body energy expenditure and BAT activity, but not as large as increase under cold conditions
No browning of WAT
Probably not very useful

351
Q

Cold-induced WAT browning - glucose

A

Increases rate of glucose uptake by BAT - more than insulin stimulates glucose uptake by skeletal muscle

352
Q

Cold-induced WAT browning - cold exposure increased … in existing BAT of mice

A

Both glucose and fatty acid uptake

353
Q

Cold-induced WAT browning - cold and capsinoid exposure increases…

A

Conversion of WAT to BAT

Correlated with increased body energy expenditure

BIOSCI 106 (6 decks)

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