fat metabolism and exercise Flashcards
what is fat
saturated fatty acids- each carbon has 2 hydorgens bound
unsaturated FA- C=C bond, not all carbons are saturated with h bonds
cis- hydrogens on same side of double bond
trans- hydrogens on opposite side of double bond
where is fat
lots more fat compared to carbohydrates
adipose tissue~12kg
intramuscular triglycerides (IMTG)~0.3kg
plasma TAG~ 0.004kg
plasma FFA~ 0.0004kg
lipid droplets
how we store fat
can be found between myofibrils (intermyofibrillar)
or found between the sarcloemma- subsarcolemmal
found in close association to mitochondria - this is where we oxidise fats
acessing fat stores
to access lipid stores in adipose or muscle tissue there are 3 stages of processing
1. lipid mobilisation
2. fatty acid activation
3. fatty acid oxidation
LM- g protein coupled receptors
GPCR are 7 pass transmembrane receptors (passes through membrane 7 times)
they have extracellular and intracellular domains
binding of a single molecule causes a conformation change in GPCR
results in binding of a g protein (GTP binding protein- has a,b,y)
G protein is formed of 3 subunits and is GDP bound
GPCR acts as GEF (guanasine exchange factor)
GTP bound alpha subunit (GAS) dissociates from beta y- becomes the active form
second messenger (cAMP)
adenylate cyclase is the downstream target of the activated G protein (GAS)
binding of GAS causes adenlyate cyclase to convert ATP to cAMP and ppi
cAMP is a 2nd messenger - transfers and amplifies an extrceullar signal to the inside of the cell
cAMP will have a further effect on cellular function
protein kinase A
enzymes that add another phosphate group to a protein-changing their own function
cAMP binds to inactive form of PKA
activates PKA
PKA phosphorylates hormone sensitive lipase (HSL) , adipose triglyceride lipase (ATGL), perilipin proteins (PLIN)
phosphorylation of these priteins stimulate lipolysis from lipid droplets
regulation of lipolysis
lipolysis- breakdwon of triaclylgycerides
PLIN proteins restrict access to lipid droplet - in this case bind to CGI-58 - acts as a coactivator of ATGL
causes it to releases CGI58 and bind to ATGL, causing lipolysis
HSL is present in cytosol under basal conditions
upon phosphory;ation by PKA it moves to the lipid droplet and binds to PLIN proteins
can now stimulate lipolysis
stages of lipolysis
TAG> DAG + FA (adipose triglyceride)
DAG> MAG + FA(hormone sensitive lipase)
MAG> FA + glycerol - monoacyl glycerol lipase
fatty acid metabolism
fatty acids liberated from the adipse tissue are released into the blood
fatty acids are not soluble in aqueous soltuins such as blood so they need to be bound to something
albumin transports fatty acids in the blood
glycerol is released to the blood and absorbed by the liver
it is converted to glyceraldehyde 3 phosphate and either:
- enters glycolysis (G3-P is a glycolytic intermediate)
- undergoes gluconeogenisis (formation of glucose)
fatty acid entry into muscle cell
FA are released from albumin and transported into the cell through the membrane protein cd36/fat (fatty acid translocase)
CD36 delivers the FA to the outer leaflet of the plasma membrane and then it flip flops across (from outer to inner membrane)
it gets bound by FABPpm (fatty acid binding protein) and takes it into the cytosol
cytosol is aqueous so FA needs a carrier- the FABP
fatty acid activation
in the cell, FA needs to gain entry to mitochondria
first step is activation
- FA reacts with coenzyme A to form fatty acyl co A
- atp is used to hydrolyse it (produces amp +ppi)
- occurs in outer mitochdondrial membrane
entry to mitochondria
site of fatty acid oxidation - matrix of mitochondria
is impermeable to almost everything
need carnitine and enzyme to enter
CPT1 on OMM transfers carnitine to acy coA to form acyl carnitine
acylcarnitine moves through a porin on OMM and in intermembrane space
on inner mitochorndrial membrane- acyl carnitine transporter transports acylcarnitine into matrix and carnitine leaves
CPT2 reverses CPT1 reaction, regenerating acyl coA and leaving carnitine to exit matrix
fatty acid oxidation
B oxidation
inside the mitochondrial matrix- acyl coA has access to the enzymes of B oxidation
B oxidation is a pathway which oxidises fatty acids (acyl coA)
consists of 4 reactions- 2x oxidation (redox), 1x hydration + 1 x thiolysis
products = FADH2, NADH + acetyl coA
for each round of b oxidation- acylcoA carbon chain is reduced by 2 carbons
the remaining acylcoA reenters the cycle until you are left with just 2 carbons forming acetyl coA
generation of atp from fats
acetyl enters tca cycle
NADH and FADH2 enter etc at complexes 1 and 2 respectively
fats are energy dense
energy is stored in organic molecules as covalent bond energy
FA have more than 22 carbons in their backbone
glucose oxidation- 32ATP
palmitic acid= 106ATP