Energy production: lipids Flashcards
List the fat-soluble vitamins
K,A,D,E
Where is the glycerol from dietary triglycerides metabolised?
Liver
Why do red blood cells not metabolise fatty acids?
They do not have mitochondria
Why does the brain not metabolise fatty acids?
Fatty acids can not easily pass through the blood-brain barrier
What hormones increase fatty acid mobilisation from adipose tissue?
Adrenaline and glucagon
What hormone decreases fat mobilisation from adipose tissue?
Insulin
How are fatty acids transported from adipose tissue to the consumer tissues?
Bound to albumin
How would you describe the state of stored triglycerides in adipose tissue?
Dynamic state - they are constantly being broken down and recycled back to TAGs again
What is the effect of low extracellular glucose on adipose tissue?
Low glucose uptake into the adipose tissue -> decreased synthesis of glycerol from glycolysis intermediates -> less TAG synthesis -> fatty acids build up in tissue -> released into blood as an alternative fuel
What are some features of fatty acids?
Saturated or unsaturated
Amphipathic
Why are some polyunsaturated fatty acids essential (i.e. required by diet)?
Because mammal cannot introduce a double bond beyond C9
Name an essential fatty acid
Linolenic acid
Where does fatty acid metabolism occur?
Mitochondria
What has to happen to fatty acids before they can be transported into mitochondria?
They have to be activated by linking to coenzyme A, to create a high energy bond:
fatty acid + CoA + ATP -> fatty acyl CoA + AMP + 2Pi
Which enzyme catalyses the linkage of CoA to fatty acids?
fatty acyl CoA synthase
Activated fatty acids (fatty acly-CoA) do not readily cross the inner mitochondrial membrane. How are they transported across?
Carnitine shuttle: Intermembrane space: Carnitine + FA-CoA -> FA-Carnitine + CoA Mitochondrial matrix: FA-carnitine + CoA -> Carnitine + FA-CoA
Which enzymes catalyse the transfer of fatty-acyl to carnitine and then back to CoA?
CAT1 and CAT2
Carnitine acyltransferases
What is notable about the carnitine shuttle transporter?
It transports acetyl carnitine into the matrix whilst simultaneously transporting carnitine out of the matrix
How is the carnitine shuttle regulated ( and therefore regulates the rate of FA oxidation?
Inhibited by malonyl-CoA (biosynthetic intermediate of FA synthesis)
What do defects in the carnitine shuttle transport system cause?
Exercise intolerance and lipid droplets in muscle
In fatty acid catabolism 2C (acetyl) is removed on each cycle producing which other products?
FADH2
NADH
H+
What does fatty acyl-CoA require for catabolism to occur?
H2O (one per cycle)
FAD (one per cycle)
NAD+ (one per cycle)
CoA
What are the products of fatty acid catabolism used for?
acetyl-CoA -> TCA cycle
FADH2 + NADH + H+ -> oxidative phosphorylation
What happens to fatty acid oxidation in the absence of O2?
It stops as NAD+ and FAD are required in their oxidised forms for the fatty acid cycle
Glycerol from adipose tissue or from enterocytes (dietary TAGs) can be transported to the liver in the blood. In the liver it is activated by what enzyme into glycerol phosphate?
Glycerol kinase
What are the two metabolic routes that glycerol phosphate can go down in the liver?
Glycolysis: conversion to DHAP + NADH
TAG synthesis: esterification with fatty acyl-CoA
Linkage of acetyl to CoA has what effect?
Creates a high energy of hydrolysis bond (linked via S-atom), therefore activates the acetyl group
Why do we require vitmain B5 in our diet?
It cannot be synthesised in the body and is used in the synthesis of CoA
Acetyl is an important intermediate in which anabolic and catabolic pathways?
- Fatty acid synthesis (TAGs, phospholipids)
- TCA cycle
- HMG synthesis (ketone bodies, cholesterol (steroid hormones))
Where are the three ketone bodies synthesised in the body?
- Liver - acetoacetate and beta-hydroxybutyrate
2. Liver? blood - acetone (by non-enzymatic spontaneous decarboxylation)
How is HMG-CoA synthesised?
From acetyl-CoA by HMG-CoA synthase (+ acetoacetly CoA)
How are ketones synthesised from HMG-CoA
HMG-CoA lyase converts to acetoacetate. Acetoacetate can be spontaneously converted to acetone or enzymatically converted to beta-hydroxybutyrate
How is cholesterol synthesised from HMG-CoA?
By the enzyme HMG-CoA reductase:
HMG-CoA -> Mevalonate -> cholesterol
How do statins work?
Inhibit the enzyme HMG-CoA reductase and therefore the synthesis of cholesterol in the liver
Why does increased fatty acid oxidation divert acetyl CoA into ketone body synthesis?
Fatty acid oxidation uses lots of NAD+ and therefore high levels can lower the [NAD+] (low substrate availability) and increase [NADH] (product inhibition) so much that it inhibits the two irreversible steps (isocitrate dehydrogenase and alpha-ketoglutarate dehydrogenase) of the TCA cycle. This causes acetyl CoA to be diverted from the TCA cycle into ketone body synthesis
beta-hydroxybutyrate and acetoacetate are transported in the blood to tissues (with mitochondria). How are they used as fuel molecules?
Converted back to acetly CoA.
- Acetoacetate -> acetyl CoA
- Beta-hydroxybutyrate + NAD+ -> acetoacetate + NADH (and then converted to acetly CoA as in 1.)
When does cholesterol synthesis occur?
When high insulin:glucagon ratio -> lyase inhibited, reductase activated
When does ketone body synthesis occur?
When insulin: glucagon ratio low -> lyase activated, reductase inhibited
E.g. in starvation or diabetes
What is the use of ketone bodies in starvation/diabetes?
Spares glucose (for brain) by converting fatty acids into ketone bodies in the liver which can then circulate in the blood and provide tissue with mitochondria acetly CoA for the TCA cycle. Later on in starvation when glycogen stores have been depleted, protein will need to be broken down to produce glucose by gluconeogenesis
How are fatty acid with an odd number of carbon atoms oxidised?
Beta-oxidation until 3C unit (proprionyl CoA), which can undergo:
- Carboxylation by carboxylase -> methyl malonyl CoA (biotin cofactor)
- Rearrangement by mutase -> succinyl CoA (Vitamin B12 cofactor)
How do ketone bodies conserve glucose for utilisation in the brain?
Ketone bodies are converted to acetyl CoA which:
- inhibits pyruvate dehydrogenase
- inhibits PFK (via production of citrate in TCA cycle) -> [glucose-6-P] increases which:
(i) inhibits hexokinase (product inhibition)
What happens to the rate of lipolysis as ketone body concentration increases?
It decreases to conserve fatty acids
