L10- Lipid metabolism Flashcards
lipids are
insoluble- hydrophobic
lipids most commonly contain
C, H and O
-
phospholipids also contain
P and N
lipids are more …. than carbohydrates
reduced
what does it mean if lipids are more reduced than CHOs
release more energy when oxidised (requires more oxygen too)
classes of lipids
- Fatty acid derivatives
- Hydroxy-methyl-glutaric acid derivative (C6 compounds)
- Vitamins
Fatty acid derivatives
- Fatty acids- fuel molecules
- Triglycerides (TAG)- fuel storage and insulation
- Phospholipids- membranes
- Eicosanoids
Hydroxy-methyl-glutaric acid derivative (C6 compounds)
- Ketone bodies- water soluble fuel molecules
- Cholesterol- membrane and steroid hormones
- Cholesterol esters
- Bile acids and salts
vitamins
A, D, E, K
Triglycerides (TAG) structure
- Glycerol backbone
- Fatty acid side chain
- Hydrophobic
- Amphiphatic
- Formed via esterification
TAG stored in
anhydrous form in adipose tissue
when is TAG utilised
prolonged exercise, starvation and during pregnancy
TAG gets hydrolysed to
glycerol and fatty acids
fatty acids produce how much of the energy of TAG
95% (B-oxidation)
glycerol produces how much of the energy of TAG
5% ( glycolysis)
TAG cannot be used by
cells without mitochondria
e.g. RBC and the brain (FA cannot pass BBB)
outline how triglycerides (TAG) is metabolised
- Triglycerides (TAG/ dietary lipids) eaten
- In the GI tract (small intestine) TAG is hydrolysed by pancreatic lipases
- TAG Glycerol + fatty acids
o Glycerol - Glycerol is absorbed into the blood from the small intestine
- Glycerol in the blood is transported to the liver
- Where it is used as a precursor to synthesise glucose
o Fatty acids - FAs absorbed into the blood from the small intestine after TAG is broken down
- In the GI tract fatty acids are converted back to TAG
- In the blood TAG is then transported to the adipose tissue by lipoprotein particles called Chylomicrons
- Stored as TAG in adipose tissue
- Released as fatty acids when needed and carried to consumer tissues as albumin-fatty acid complex
- FA oxidation leads to release of ATP (energy)
structure of fatty acid
CH3(CH2)nCOOH
- sat or unsatisfyingly
unsat
at least one double carbon bond)
name a FA is an essential requirement for the diet
linolenic acid
FA metabolism simple: consumer tissue vs adipose tissue
- Consumer tissue = FA oxidation –>energy
- Adipose tissue (Stored as TAG) –> Fat mobilisation-hormone sensitive lipase
o Increase- glucagon/adrenaline
o Decrease- Insulin
when is TAG mobilised from adipose tissue
glucagon or adrenaline
fatty acid metabolism summary
Where? The mitochondria
- FA is activated by linking Coenzyme A outside the mitochondrion
- FA is transported across the inner mitochondrion using a carnitine shuttle
- FA cycles through sequence of oxidative reactions, with 2 Carbons removed each cycle- B-oxidation
we want to oxides the fatty acid to
extract as many electrons as possible so that they can be transferred to electron carrying molecules like NAD+ and FAD+, so that NADH and FADH2 can be used to produce ATP on the electron transport chain.
fatty acid activation
Fatty acyl CoA synthase links Coenzyme A to fatty acid
activated fatty acids (Acyl-CoA)
do not readily cross the inner mitochondrial membrane
what is coenzyme A derived from
vitamin B5
outline the carnitine shuttle of fatty acyl-CoA
- Fatty acyl-CoA (activated fatty acid) binds to carnitine to produce Acyl Carnitine (losing CoA)
- Acyl carnitine is then transported across the mitochondrial membrane via the Carnitine shuttle transporter
- Once within the Acyl Carnitine loses carnitine and recombines with CoA to form Acyl-CoA
what inhibits carnitine shuttle
malonyl-CopA
B-oxidation of Acyl-CoA
Where activated fatty acid chain get oxidised within B-oxidation cycle, which breaks the off 2 carbon chains per round- H+ and e- transferred to NADH and FADH2 (oxidation in ETC)
2 carbon chains produced via B-oxidation are caleld
Acetyl Co-A
Acetyl CoA prodded from B-oxidation
enter Kreb cycle and then the ETC to produce ATP
glycerol is transported in the blood to the
liver where it is metabolised
in the liver what starts the metabolism of glycerol
glycerol kinase
Converts glycerol to glycerol phosphatw
glycerol phsophate
1) Can be converted to DHAP and used in glycolysis to produce some ATP and reducing power (NADH/FADH2)
2) Or be used in the synthesis of triglycerides
acetyl coA is the main
convergence point for catabolic pathways
Acetyl CoA function
act as an important intermediate in both catabolic and anabolic pathways
ketones are
water soluble molecules, which are alternative substrates to glucose and fatty acids
three types of ketone body synthesised in there liver mitochondria (from fatty acids)
- Acetoacetate (liver)
- Acetone
o Spontaneous decarboxylation of acetoacetate - B-hydroxybutyrate (liver)
normal plasma ketone conc
<2mM
starvation plasma ketone body (physiological ketosis)
2-10mM
untreated type 1 diabetes (pathological ketosis)
> 10mM
stains inhibit the enzyme
HMG-CoA
HMG-CoA reductase catalyses
production of cholesterol from acetyl coA
Ketoacidosis
- characteristic smell of acetone on breath when acetone excreted via the lungs
- Acetoacetate and B-hydroxybutyrate are strong organic acids.
ketones above renal threshold
excreted in the urine (Ketonuria)
Regulation of ketone body synthesis by insulin/glucagon (fed/starved) ratio
- Ketone bodies and early starvation:
Ketones spare glucose in early starvation/diabetes
- release of glucagon in reaction to starvation (increase ketone bodies production)
- Triglycerides go through lipolysis to produce fatty acids which are released from adipose tissue
- These circulate to the liver where the fatty acids undergo ketogenesis where ketone bodies are produced
- Ketone bodies are broken down to acetyl CoA where they are used to produce ATP via the TCA and ETC
Regulation of ketone body synthesis by insulin/glucagon (fed/starved) ratio
- ketone bodies in well fed state
release of insulin’s stimulates production of cholesterol from acetyl CoA
in late starvation
- Protein from muscles are hydrolysed to amino acids
- Amino acids circulate to the liver where they are converted to pyruvate
- Pyruvate goes through gluconeogenesis to produce glucose
- Glycogen in the liver is hydrolysed to produce more glucose
- Circulating glucose used to power the brain
