W8 Lipid Metabolism Flashcards
available energy of food constituents
fat (adipose tissue): 555000 k J
protein (muscle): 102000
glycogen (muscle): 1920
glycogen (liver): 1120
glucose (extracellular fluid): 320
primary sources of triacylglycerol
diet
de novo biosynthesis in liver
storage depots in adipocytes or adipose cells
fats insoluble > emulsified first with bile salts or complexed proteins to form lipoproteins
how do hormones trigger the release of fatty acids from adipose tissues
synthesis of TAG and its deposition in adipose cells unlimited
mobilisation of stored fat (lipolysis) hormonally controlled by cAMP
mediated by Epi during stress and glucagon during fasting
other hormones regulate process under different conditions
how are fats mobilised from dietary intake
alkaline pancreatic juice secreted into duodenum > raise pH of digestive mixture > hydrolysis of tracylglycerols by pancreatic lipase and non specific esterase
how does bile salts help fat mobilisation during dietary intake
act as detergents to emulsify triglycerols and facilitate hydrolytic activity of lipases and esterase
fatty acids pass into epilethial cells > condensed with glycerol > form new triacylglycerols > aggregate with lipoproteins to form particles called chylomicrons
difference between bile acids and bile salts
bile acids produced in liver from cholesterol > bile acid colic and chenodeoxycholic acid > found in unconjugated forms
COOH in bile acid reacts with either glycine or taurine > conjugated form of bile acids > form bile salts
how do bile salts emulsify TAGs in the intestine
cholic acid ionises to give cognate bile salt
hydrophobic surface of bile salt associates with triacylglycerol > complexes aggregate to form a micelle
hydrophilic surface of bile salt faces outward > allow micelle to associate with pancreatic lipase/colipase
hydrolytic action of lipase/colipase frees fatty acids to associate in much smaller micelle > absorbed through intestinal mucosa
generalised structure of plasma lipoprotein
hydrophobic inner core composed of cholesterol esters and tryacylglycerols surrounded by a hydrophilic surface formed by polar head groups of phospholipids and free cholesterol
classification of lipoproteins
chylomicron: delivery of dietary fatty acids
VLDL: delivery of dietary and other fatty acids
IDL: delivery of dietary and other fatty acids
LDL: delivery of cholesterol
HDL: picking up excess cholesterol from cells for delivery back to liver
what is the active site of lipoprotein lipase made up of
Ser, His and Asp
first step of fatty acid oxidation
activation: fatty acid activated using coenzyme A and ATP > produce fatty acyl-CoA
second step of fatty acid oxidation
fatty acyl-CoA cannot cross mitochondrial membrane but must be transported to mitochondrial matrix
carnitine (amino-oxy acid) undergoes ester-formation exchange reaction with fatty acyl-CoA > fatty acyl-carnitine ester that can move across membrane via facilitated diffusion
third step of fatty acid oxidation
beta oxidation pathway
3 main properties of the beta oxidation pathway
fatty acids must be degraded by oxidation at beta carbon followed by C(alpha)-C(beta) bond
this degradative process takes place in mitochondria
acetyl-CoA is released
difference between beta oxidation in mitochondria and in peroxisomen
mitochondria: provides energy to organism
peroxisomen: responsible for shortening long chain fatty acids that are poor substrates for mitochondrial beta oxidation
how does acyl-CoA synthetase activates fatty acid
fatty acid reacts with ATP > acyl adenylate (fatty acyl-AMP)
fatty acyl-AMP reacts with CoA > fatty acyl-CoA (activated form of fatty acids)
AMP is released
how does the carnitine cycle help transport fatty acyl-CoA into the mitochondria
fatty acyl CoA converted to O-acylcarnitine using carnitine transferase I on outer mitochondrial membrane > release CoA > transported into inner membrane via translocase
acylcarnitine passed to carnitine transferase II on matrix side of inner membrane > transfers fatty acyl group back to CoA > reform fatty acyl CoA > leaving free carnitine > return across the membrane via translocate
energy yield from oxidation of fatty acid
each round of oxidation produces one NADH, one FADH2 and one acetyl-CoA
oxidation of acetyl-CoA via citric cycle generates additional FADH2 and NADH > deoxidised through oxidative phosphorylation to form ATP
where does oxidation of different fatty acids take place in
very long chain and long chain: peroxisome
medium chain and short chain: mitochondria
how many atp produced per round of beta oxidation
each round > 2 carbon cleaved
1 NADH, 1 FADH2 and 1 acetyl CoA
acetyl coA goes into TCA > 3 NADH and 1 FADH2 and 1 GTP=1ATP
total atp = 17
difference between beta oxidation in mitochondria and peroxisomes
mitochondria: ubiquinone is reduced in first step
peroxisomes: hydrogen peroxide produced
how are fatty acids with odd number carbon chain oxidised
last step > 3C propionyl coA produced > carboxylation using propionyl-CoA carboxylase + biotin > D-methylmalonyl-CoA > L-methylmalonyl-CoA using methylmalonyl-CoA epimerase > succinyl coA using methylmalonyl-CoA mutate > enter TCA cycle to produce ATP
definition of ketogenesis
process in which acetyl-CoA is converted to three metabolites: acetone, acetoacetate and beta hydroxybutyrate
ketone bodies synthesised primarily in liver but important sources of fuel and energy for many tissues
how is beta hydroxybutyrate converted into acetyl coA
oxidised into acetoacetate by beta hydroxybutyrate dehydrogenase > acetoacetate coA transferase transfers coA from succinyl-CoA to acetoacetate > acetoacetyl-CoA > split into two molecules of acetyl CoA by thiolase
what is the Lynen cycle
the formation of acetoacetate from two molecules of acetyl-CoA > formation of two HSCoA and 1 acetoacetate
how is acetyl coA converted to malonyl coA to be the starting material for fatty acid synthesis
acetyl coA carboxylase (ACC) contains a biotin prosthetic group
ATP activates bicarbonate > carboxyphosphate > carboxyl group transferred to biotin > biotin transfers carboxy group to acetyl coA > form malonyl coA
how is acetyl coA carboxylase regulated
activation by citrate: citrate promotes polymerisation of inactive ACC dimers into active polymeric form > allosterically activates ACC
inhibition by palmitoyl-CoA (final product of fatty acid synthesis): it seres as negative feedback inhibition
