Metabolism - Lec 6 Flashcards
Lipids are insoluble generally reduced molecules that release alot of energy when oxidised
what are the classes of lipids ?
- Vitamins - A,E,D,K
- Fatty acid derivatives - Fatty acids (fuel), Triglycerides - fuel storage, phospholipds for the membrane
- Hydroxyl-methyl-glutaric acid derivatives (C6) -Ketone bodies, Choleterol (membranes and hormones)
describe the structure of triacylglyserides (triglycerides)
where are they stored, how are they used ?
Glycerol backbone of 3 carbons
each has a fatty acid side chain attached
produced by esterification, broken by lypolysis
TAG’s are hydrophobic , stored in adipose tissue -used in prolonged exercise and starvation
storage is under metabolic/hormonal control
how are tissues involved in triglyceride metabolism ?
TAG’s are hydrolised (broken down) by pancreatic lipases into glycerol and Fatty acids - this happens in the small intesitne
Glycerol - gi tract -> blood -> Liver
Fatty acids - Gi tract ->combined with glycerol and transported by Chylomicrons (a lipoprotein partice that solublsie’s fat for transport) -> Adipose (stored as TAG) -> converted to fatty acids - FA albumin complex transports to muscle for use needed
this occurs when glucagon or adrenaline is high and insulin is low, using a hormone sensitve lipase
what are chylomicrons ?
a lipoprotein partice that solublsie’s fat for transport
explain and draw the fatty acid cycle in Adipose tissue
- glycerol 1- P feed out of glycolysis in adipose tissue
- —Glucose 6 - P (G 6 P) freely interconverts to G-1-P) - undergoes esterification to a triglyceride, stored here in adipose tissue
- undergoes lysis to produce fattys acids and glycerol
- Glycerol and fattys acids can be used via different pathways in glycocsis to produce pyruvate then energy
- Fatty acids can also be converted to Fatty acyl CoA - this esterification with Glycerol-1-Pto produce triglyceride ( completes cycle to rejoin step 2.)
Low glucose levels will result in fatty acid release as an alternative fuel
Fatty acids are….
amphipahtic
saturated or unsaturated (double bond c)
some polyunsaturated fats are essential as we cannot introduce the double bonds
how does fatty acid metabolism work ?
mitochondrial
FA is acitvated by linking with Coenzyme A ouside the mitochondria - this uses Fatty acid CoA synthase - this process requires an ATP, produces and AMP and 2Pi
cartinine shuttle transports across the membrane into mitochondria
Sequence of Oxidative reactions Losing C2 each time
produces NADH2 and FADH2 each cycle
this is a Beta oxidation - it occurs in most tissues and WBC’s
does not occur in brain and RBC’s
the reaction will stop in absence of O2
NO ATP is synthesised but the NADH and FADH2 can be used to produce ATP
how does the carnitine shuffle work ?
Carnitine + acyl CoA ——–> acyl carnitine + CoA (INTERMEMBRANE SPACE)
Acyl carnintine is punped into matrix by carnitine shuttle transporter
acyl carnintine + CoA —–> Carnintine + Acyl CoA (MATRIX)
Carnitine is pumped out to the intermembrane space as Acyl Carntine is pumped in
the reaction is assited by Carnitine 1 acyltransferases and 2
this can be inhibited by malonyl CoA
it is regulated so controls the rate of FA oxidaiton
how does energy produced compare between sugar and fat
more energy is derived from FA oxidation than glucose oxidation
Fats contain more energy than sugars
How does glycerol metabolism work ?
glycerol is transported in the blood to the liver where it can be metabolised
glycerol + ATP —————–> Glycerol Phosphate + ADP
Glycerol Kinase
then it can be used in Triacylglyeride synthesis
or Glycerol phosphate + NAD+ Dihydroxyacetone phosphate (DHAP)
DHAP can interconvert to glyceraldehyde-3-P which is an intermediate of glycolysis
why is Acetyl CoA vital to the human body ?
important intermediate in both catabolic and anabolic pathways
Main convergence point for catabolic pathways
what are ketone bodies ?
give some clinical importance
body produces 3 ketone bodies -
Acetoacetate, Acetone (given off in breath-smell)and B-hydroxybutyrate
untreated type 1 diabetics can undergo Pathological ketosis - where conc is over 10mM
excreted in urine if above renal threshold - ketonuria
ketone bodies are strong acids - can cause ketoacidiosis - think type 1 diabties
this can give a fruity (ketone smell) on the breath
where are ketone bodies produced ?
the liver mitochondria
How are ketone bodies produced ?
triglycerides undergo lypolysis to produce fatty acids—> Acetyl CoA + (synthase) ——–>HMG (hydroxymethyl CoA) —-> ketone bodies
HMG-CoA reductase will divert path and convert acetyl CoA to cholesterol
fatty acids produce the ketone bodies during starvation
explain Metabolism of ketone bodies ?
ketone bodies are produced in liver - carried in the blood- metabolised by TCA cycle in muscle
