Protein control: (leyland) lipid metabolism 2

Question 1

Where does fatty acid synthesis occur?

Answer 1

Cytoplasm in liver and adipose cells

Question 2

Key enzyme of regulation in FA synthesis?

Answer 2

Acetyl CoA carboxylase -> first step of cycle

Question 3

How many carbon atoms are added per ‘linked reaction’ in fatty acid synthesis?

Answer 3

2C

Question 4

How is Acetyl CoA carboxylase regulated? Activated and deactivated how?

Answer 4

Phosphorylation/Dephosphorylation

Phosphorylation + Inactivation
AMP-activated protein kinase (activated by low energy -> presence of AMP in cell, also glucagon)
-> enzyme phosphorylates Acetyl CoA carboxylase and inactivates it

Dephosphorylation + activation
Protein phosphatase 2A (activated by insulin)
-> enzyme dephosphorylates Acetyl CoA carboxylase and activates it

also Allosteric activation by citrate and inhibited by products of FA synthesis

Question 5

Where does acetyl CoA for FA synthesis come from?

Answer 5

Excess CHO is converted to acetyl CoA via glycolysis (oxidation of glucose)

Excess protein converted to acetyl CoA via pyruvate dehydrogenase activity or directly

Question 6

Describe process of fatty acid mobilisation in the fasted state

Answer 6

PKA activates Perilipin -> activates ATGL (adipose triglyceride lipase)
-> converts TAGs to DAGs

PKA also activates Hormone Sensitive (HS) lipase
-> converts DAGs to MAGs

MAG lipase converts to glycerol + FA

Question 7

Which process causes energy release from fatty acids?

Where does it occur and what are the reactants + products?

Answer 7

Beta-oxidation -> occurs in mitochondria

Cycles though sequences of reactions, 2C removed each step

1NADH and 1FADH2 produced each cycle

all intermediates linked to CoA

Question 8

Key regulatory steps in Beta-oxidation of FAs?

Answer 8

Transport of fatty acetyl CoA into mitochondria
+++ malonyl CoA -> FA oxdn decreases
— malonyl CoA -> FA oxdn increases

Inhibition of enzyme activity by high energy signals

Control of availability of FAs
- insulin inhibits HSL -> decreases rate of FA release

Transcriptional regulation
- insulin inhibits transcription via Insulin responsive element (IRE)

Question 9

When might an increase in the oxidation of fatty acids be needed?

Answer 9

Increase in demand for ATP that cannot be met by an increase in glucose oxidation
e.g. skeletal muscle during sustained physical activity

Provide an alternative fuel to glucose during starvation
-> FA oxidation slows rate of glucose utilisation

Provide alternative fuel to glucose during trauma, proliferating cells require glucose for growth

During stress to provide energy for flight or fight response

Question 10

Purpose of ketone bodies?

Answer 10

Produced when fat breakdown predominates e.g. fasting, diabetes

Alternative fuel source

Question 11

Describe biosynthesis of cholesterol

Answer 11

Three acetate condense to form mevalonate

Mevalonate converts to 5-C isoprene

Six isoprene polymerise to form 30-C linear squalene

Squalene cyclises to form the four rings that are midified to produce cholesterol

Question 12

Rate limiting step of cholesterol synthesis?

Answer 12

HMG-CoA reductase (formation of mevalonate)

Question 13

Regulation of cholesterol synthesis?

Answer 13

Sterol dependent regulation of gene expression

Sterol accelerated HMG-CoA reductase degradation

Reversible phosphorylation