Lipids cont: ketone bodies, storage and non-mammals

Question 1

When are ketone bodies formed?

Answer 1

B oxidation needs acetylCoA, from oxaloacetate, from pyruvate
Lack/mishandling of carbs i.e. pyruvate, acCoA accumulates in mc matrix – ketone bodies

Question 2

Ketone body synthesis

Answer 2

3 acyl-CoA = HMG-CoA

Converted in acetoacetate –ketone bodies e.g. hydroxybutyrate

Question 3

Ketones as fuel

Answer 3

Heart, skeletal muscle, brain, kidney
Water soluble, so can pass blood-brain barrier
Tissues break ketones back down to CoA for CAC

Question 4

Why are ketone bodies synthesised in the liver?

Answer 4

Does not contain CoA transferase and lacks oxaloacetate for CAC

Question 5

Role of ketones?

Answer 5

Survive carb shortages
Can be oxidised in CAC so can replace glucose in tissues, sparing glucose for dependent cells e.g. RBCs
Prevents breakdown of muscle protein in starvation by reducing need for gluconeogenesis
CoA from acetyl-CoA molecules - FA oxidation for ATP

Question 6

Diabetic ketoacidoses

Answer 6

Increase FA B oxidation in bloodstream through low insulin
Activates gluconeogenesis: oxaloacetate down, acetyl-CoA up = ketone bodies

Acidic ketones accumulate (bad) = acidosis

Question 7

Ketosis in starvation

Answer 7

Glycogen used up, blood glucose falls, insulin drops

Lipolysis increases = FA oxidation in liver

Gluconeogenesis increases with FA as fuel

Ketone bodies produced as gluconeogenesis uses up oxaloacetate, building up acetyl-CoA

Question 8

FAs in plants/algae?

Answer 8

Often polyunsaturated PUFAs, in fish and seed oils
Synthesised in chloroplasts
Stored as TAGs, often in seeds

Question 9

FA synthesis in plants?

Answer 9

Pyruvate – acCoA – malonyl-CoA intermediates

Completed FAs usually 16-18 c

ACCase key enzyme as in animals, but is a multi-complex enzyme (just one in animals) more like bacteria
FASII is also a complex

Complexes = greater regulation

Question 10

Chloroplast FA desaturation and regulation

Answer 10

Fatty acid desaturase, another regulatory component;
Stimulated by sunlight i.e. photosynthesis = FA synthesis
Oleic acid accumulation (end product of desaturase) = inhibition to avoid toxicity

Question 11

Essential FAs

Answer 11

PUFAs - animals cannot synthesise

Linoleic acid - structural membrane
A-linoleic acid - precurser

Arise in plants due to ER-localised desaturases, e.g. FAD2 = linoleic, FAD3 = A-linoleic

Question 12

Lipid modification in plants

Answer 12

Acyl carrier proteins removed from FAs before export from chloroplasts

CoA binds acyl group as it passes membrane = cytoplasmic pool of acyl-CoA bound FAs

Modified in ER e.g. by desaturation converting acyl-CoA bonds FAs to phospholipids using LPCAT

LPCAT - another key regulatory enzyme

Question 13

Omega FAs

Answer 13

Last carbon = omega
omega3 = double bond on third carbon from end, omega6 = double bond on 6th from end

These are essential, as they are precursors of eicosanoids

Question 14

Eicosanoids

Answer 14

Signalling molecules used in inflammation e.g. prostaglandins, leukotrienes

Linoleic acid (omega6) derived = pro inflammatory

A-linoleic acid (omega3) derived = anti inflammatory

Question 15

Omega 3s?

Answer 15

From a-linoleic = EPA and DHA

Produced in algae, not plants

Question 16

Omega 6s?

Answer 16

From linoleic = AA

Question 17

FA chain elongation in plants(forming omega3 and 6s)

Answer 17

Used 4-protein elongase at ER membrane

Sequential desaturase and elongase reactions to trasnfer phospho and acyl groups (5B for diagram)

Question 18

FA storage in plants

Answer 18

Stored as triacylglycerol, synthesised in ER by Kennedy Pathway

Question 19

Kennedy Pathway

Answer 19

TAG synthesis pathway, as in eukorayotes
Using G3PAT, LPA AT, PAP, DAG AT
Adding acyl-CoA to each intermediate from pool in cytosol, derived from FA export from chloroplasts

Question 20

Modifications of TAGs in photosynthetic organisms

Answer 20

Occurs in ER;
Elongation/desaturation of chains
Integrate phosphatidylcholine into DAGs

Question 21

Classical pathway of de novo DAG synthesis

Answer 21

Conserved in eukaryotes

G3P — lysophosphatidic acid – phosphatidic acid – DAG

Question 22

PC-derived pathway of de novo DAG synthesis

Answer 22

Phosphatidylcholine (PC) modified e.g. desaturation and then – DAG

Question 23

DAGs – TAGs

Answer 23

Classical de novo: DG AT with acyl-CoA (adding acyl)

PC derived: PD AT, reversible

Question 24

Commercial use of plant FAs

Answer 24

TAGs - energy and fuel
FAs, omega 3s - pharma,cosmetics
Omega 3s, TAG oil - nutritional supplements

Question 25

Issues with engineering plants for FAs

Answer 25

Don’t fully understand lipid metabolism
Only some plants/algae produce certain PUFAs
Some only produce 18c FA chains
May be able to target acyltransferases for specific FAs