Cell Metabolism 2

Question 1

What are the 5 main classes of lipids?

Answer 1

Free fatty acids

Triacylglycerols

Phospholipids

Glycolipids

Steroids

Question 2

What is the difference between saturated and unsaturated fatty acids?

Answer 2

Saturated - no double bonds

Unsaturated - at least one double bond

Question 3

How are fatty acids often stored?

Answer 3

In the form of triacyglycerols

Three fatty acids attached to one glycerol by water linkages

This neutralises the carboxylic acid groups, keeping the pH in cells within normal ranges

Question 4

What makes fatty acids an ideal storage molecule?

Answer 4

Reduced

Anhydrous

Question 5

At which point do fats join into cellular metabolism?

Answer 5

Fats—> fatty acids and glycerol —> acetyl CoA

This goes into the TCA cycle

It is produced in the mitochondria

Question 6

What are the three primary sources of fats?

Answer 6

The diet

De novo synthesis in the liver

Storage depots in adipose

Question 7

How are dietary fatty acids made soluble?

Answer 7

Bile salts

Made of cholic acid
They have a hodrophobic and a hydrophilic plane
They associate with triacylglycerols to form a Micelle
lipase then digests them

Question 8

Where are bike salts generated and stored? What do they do?

Answer 8

Generated by the liver

Stored in the gall bladder

Bile salts emulsify fats in the intestine aiding in the digestion and absorption of fats and fat-soluble vitamins (A,D,E,K)

Question 9

What happens whenever there is a lack of bile salts?

Answer 9

The majority of fat passes through the gut resulting in Steatorrhea (fatty stool)

Question 10

How does Orlistat work in treating obesity?

Answer 10

A potent inhibitor of gastric and pancreatic lipases

Reduces fat absorption by 30%

Effective in treating obesity for up to two years

Main side effects are abdominal pain, urgency to defacate, flatus, steatorrhea

Question 11

How are lipids transported? How are these categorised?

Answer 11

In the plasma by lipoproteins

By density

Chylomicrons (CM
Very low density lipoproteins (VLDL)
Intermediate density (IDL)
Low density (LDL)
High density (HDL)

see table on slide for roles

Question 12

What is a chylomicron? How does it work?

Answer 12

Transport dietary fats

Products of fat digestion are absorbed by enterocytes that line the brush border of the small intestine
The triglycerides are resybthesised before they are incorporated into chylomicrons
They are transported by lymphatics into the blood stream
They acquire apoproteins from HDL

They consis of triglycerides enclosed Worthing phospholipids and apoproteins

Question 13

What is the path along which chylomicrons are transported?

Answer 13

Lea teams of the intestine to the thoracic duct to the left subclavian vein where they enter the blood stream

Question 14

What happens when chylomicrons encounter the capillary endothelial cells?

Answer 14

On the cells lining tissues such as adipose, heart and skeletal muscle, there is lipoprotein lipase which breaks down the chylomicrons and the triglycerides inside

The fatty acids undergo beta oxidation and the glycerol is returned to the liver for gluconeogenesis

Question 15

What is the anatomy of a chylomicron?

Answer 15

Phospholipid monolayer containing cholesterol and apoproteins

Surrounding score of triacylglycerols and cholesterol esters

Question 16

Chylomicrons contain cholesterol esters, how does this esterfication happen?

Answer 16

They are synthesis in the plasma from cholesterol and phosphatidylcholine (lecithin)
Reaction is catalysed by LCAT

Cholesterol +phosphatidylcholine —>
Cholesterol ester + lysophosphatidylcholine

Question 17

What is the life cycle of VLDL,LDL,IDL,HDL?

Answer 17

Cell metabolism 2 part 2 16:43

Question 18

What are HDLs?

Answer 18

“Good cholesterol”
They take cholesterol from peripheral tissues back to the liver for use (bile salts) or disposal (reverse cholesterol transport)
They lower total serum cholesterol

Question 19

What are LDLs

Answer 19

“Bad cholesterol”
Prolonged eleceation leads to atherosclerosis
Transport cholesterol from liver to peripheral tissues (over 40%) of their weight is cholesterol esters

Question 20

What is the process of fatty acid metabolism called?

Answer 20

B-oxidation
Takes place in mitochondria
Results in the generation of acetyl CoA

Question 21

What is the first step in B oxidation?

Answer 21

Fatty acids —> acyl CoA species

Fatty acid + ATP + HS CoA —>
Acyl CoA + AMP + PPi

Question 22

How is Acyl CoA moved into the mitochondria from the cytoplasm?

Answer 22

Via the carnitine shuttle

Question 23

How does the carnitine shuttle work?

Answer 23

Cytoplasm:
Carnitine + Acyl CoA —> Acyl carnitine + CoA

Using Carnitine acytyltransferase I

Matrix:
Acyl carnitine + CoA —> carnitine + Acyl CoA

Using carnitine acyltransferase II

Carnitine and Acyl carnitine are moves across the membrane by translocase proteins

Question 24

What is primary carnitine deficiency?

Answer 24

Autosomal recessive

Rare (1 in 100000 USA, 1 in 500 Faroe Islands)

Symptoms occur during childhood, including encephalopathies, muscle weakness, hypoglycaemia

Mutation in a gene which encodes a carnitine transporter.

Supplements can be taken as treatment

Question 25

What happens in the B oxidation cycle

Answer 25

Acyl CoA undergoes a sequence of oxidation, hydration, oxidation and thiolysis reactions

Results in the production of acetyl CoA and an Acyl CoA species which is two carbons shorter than the original

Required FAD, water, NAD+ , HS-CoA

The final turn produces two molecules of acetyl CoA

Question 26

Acetyl CoA produced by B oxidation only enters the TCA cycle under one condition. What is this?

Answer 26

B oxidation and carbohydrates metabolism must be balanced as oxaloacetate is needed upon entry

Question 27

What happens when carbohydrate metabolism and B oxidation are not balanced (more B oxidation) ?

Answer 27

Acetly CoA forms acetoacetate, D-3-hydroxybutyrate and acetone

These are known collectively as acetone bodies

Question 28

For example with palmitate, how much ATP is released in its metabolism?

Answer 28

129 ATP

Question 29

Which process, B ocidation or glucose metabolism, releases more energy per mole?

Answer 29

B oxidation

Question 30

How many enzymes does lipogenesis involve?

Answer 30

2
Acetyl CoA carboxylase
Fatty acid synthase

Question 31

How does lipogenesis ( fatty acid biosynthesis) occur?

Answer 31

Sequential decarboxylative condensation reactions involving acetyl CoA and malonyl CoA

Following each round of elongation the fatty acid undergoes reduction and dehydration by the sequential action of KR, DH and ER

The growing fatty acid group is linked to an Acyl carrier protein (ACP)

Question 32

What do KR, DH and ER stand for?

Answer 32

Ketoreductase
Dehydratase
Enol reductase

Question 33

What are the similarities between B oxidation and fatty acid synthesis?

Answer 33

Same except reverse

Degradation:
Oxidation, hydration, oxidation, cleavage

Synthesis:
Condensation,reduction, dehydration,reduction

Question 34

What are differences between B oxidation and fatty acid synthesis?

Answer 34

Oxidation. Synthesis
Carriers. CoA ACP

Reducing FAD/ NADPH
Power. NAD+

Location. Matrix Cytoplasm

Question 35

What is the overall reaction of lipogenesis?

Answer 35

Acetyl CoA (C2) + 7 malonyl CoA (C3) + 14 NADPH + 14 H+

—>

Palmitate (C16) + 7 CO2 + 8 CoA-SH + 14 NADP+

Question 36

Where does elongation of the fatty acid group longer than 16 carbons take place?

Answer 36

Separately from palmitate synthesis in the mitochondria and endoplasmic reticulum

Question 37

How are the fatty acid chains desaturated?

Answer 37

Using fatty Acyl-CoA desaturases

Question 38

Where in the body does FA biosynthesis usually occur?

Answer 38

Liver
Adipose
Lactating breast

HOWEVER
There is also evidence to suggest that it takes place in cancer cells. Maybe as an energy source?
So could we target FA synthetase for treatment?