Biochem Lec 20-21 Flashcards
what is triacylglycerol
also known as triglyceride or TAG and the structure consist of a glycerol backbone attached to three fatty acid chains, also known as acyl chains, as this is where extra carbons are stored
these fat molecules are mainly stored in fat cells, muscle and other tissue
what does it mean to be saturated and how is that important in fats
fatty acyl chains are saturated, meaning they have no double bonds between the carbons, and that is important to allow close packing
the chains in TAG need ti be hydrolyzed off to be used
what is the overview on fat metabolism
the TAG stored in fat cells will be hydrolyzed, broken, into glycerol and fatty acids where the glycerol goes to liver cells and undergo gluconeogenesis to become glucose while the fatty acids chains go to also liver and other tissues to undergo fatty acid oxidation to become Acetyl CoA that get used in citric acid cycle
both end up generating energy
what will cause fatty acids to break and get transported from cell into other tissues to undergo beta oxidation
the hormones epinenphrine and glucagon which are active during fast state will cause intracellular signalling through GPCRs to activate lipase, the process of signalling involve the GPCR when stimulated will activated the adenylyl cyclase which converts ATP to cAMP and that will activate protein kinase A which will phosphorylate triacylglycerol lipase and phosphorylated lipase will hydrolyze ester bonds to produce the free fatty acids and glycerol by breaking triacylglycerol into diacylglycerol and then into monoacylglycerol and by other lipases that will lead to product of 1 glycerol and 3 fatty acid chains
which enzyme is the hormone sensitive lipase
triacylglyerol lipase is the hormone sensitive lipase
what transports the fatty acid chains after they have been freed
albumin will transport them in the blood
how are free fatty acids activated in cytoplasm
the acyl chains will get trapped in cell by covalent addition of coenzyme A and the acyl CoA synthase enzyme, a ligase that uses ATP, will form the fatty acyl CoA molecule and the pyrophosphate (PPi) get hydrolyzed into 2 phosphate groups as that is favourable and what drive the reaction in forward direction
how is the side reaction of hydrolyzing pyrophosphate important for acyl CoA molecule
the reaction of breaking the pyrophosphate intop 2 phosphate groups will drive the reaction of forming acyl CoA and keeping it from going back
what makes ATP–>AMP energetically favourable
this reaction is so efficient that it is responsible for 95% of the ATP made from oxidative phosphorylation as it uses ADP as subtrate since ATP synthase can only bind ADP where the reaction go as: AMP+ATP–>2ADP–>2ATP, where the first part is catalyzed by adenylate kinase and the second part is catalyzed by ATP synthase
what is the energy required for fatty acid activation by CoA
the process require 2ATP as one will be ised for activation and other to produce ADP and the enrgy to keep acyl CoA and 1water molecule will be needed to hydrolyze PPi
where does beta oxidation occur and how does it get to where it needs to
so acyl CoA is made in cytoplasm but beta oxidation occur inside matrix so the acyl CoA has to access the matrix but it cna only enter the mitochondrial inner memrbane by the porins and is too large and water soluble to cross into matrix so requires the help of shuttle
what is the way that carnitine shuttle allow for acyl CoA to get into matrix
the shuttle consist of two enzymes and a translocase where the carnitine acyltransferase I (CAT I) enzymes is found in cytoplasmic side while the carnitine acyltransferase II (CAT II) is found in the matrix side
the CAT I will convert carnitine into acyl carnitine by transfering the acyl group of acyl CoA to carnitine and then this acyl carnitine gets translocated into matrix side by translocase enzyme of the shuttle and once in matrix then CAT II will transfer the acyl group from acyl carnitine to CoA and make acyl CoA again and free carnitine to be reused
what is point of making the fatty acyl CoA outside the matrix if it is only used in matrix
the whole idea is about regulation since having permitivity will allow for membrane to stop and let molecules come in as seen appropriate
could carnitine supplements act as magic pill and promote weight loss
no because translocase protein is saturable meaning if carnitine exceed the threshold then that will cause bottlneck effect and excess carnitine gets ridden of due to body detecting excess carnitine
what is the general rule to know how many oxidation rounds the acyl CoA will undergo
number of rounds= n/2 -1 where n is number of carbons
what is the overall beta oxidation of 16:0 CoA in mitochondria
that means the chain has only undergone the beta oxidation so:
16:0CoA+7NAD+7FADH+7H2O+7CoA–> 8acetyl CoA+7NADH+7FADH2+7H
what are teh 4 steps of beta oxidation
fatty acid oxidation occur at beta carbon which is the third carbon in fatty acid chain:
1- acyl CoA dehydrogenase: produces FADH2 and create double bond in fatty acid chain
2- hydratase comes and add water across teh double bond between B-OH
3- then dehydrogenase produces NADH and creates keto group on B-carbon in chain
4- thiolase will be the last enzyme that uses CoA to release acetyl CoA and produce fatty acyl CoA chain with 2 fewer carbons
each round end up losing 2C from chain
what is the summary for fatty acid breakdown
epinephrine and/or glucagon are required for TAG breakdown and teh fatty acids travel in blood by binding to albumin and entering tissues
fatty acids get activated in cytoplasm by acyl CoA synthetase and that requires 2ATP
the carnitine shuttle is responsible for controlling fatty acid entery into matrix in exchange for free carnitine and once in the acyl chains get broken down into beta oxidation to produce acetyl CoA, NADH, and FADH2
so beta oxidation end up producing huge amount of ATP by using the CAC and oxidative phosphorylation
what can limit teh CAC from processing the fats product as fuel
CAC use acetyl CoA from fat degradation to egenrate energy but CAC is dependant on the amount of oxaloacetate present so to make efficient ATP from fat, we need oxaloacetate and that moelcule is made from amino acids or pyruvate by enzyme pyruvate carboxylase
what are the location of fat metabolism in cell
synthesis of fats occur in cytoplasm and breakdown occur in mitochondria
what are teh steps involved in fatty acid synthesis
1- export of the mitochondrial acetyl CoA to cytoplasm for fat synthesis
2- carboxylation of acetyl CoA to malonyl CoA by acetyl CoA carboxylase (ACC)
3- using malonyl CoA to form 16:0 fatty acid chains by fatty acid synthase (FAS)
how is the import and export different between beta oxidation and fat synthesis
CoA was teh reason behind aceyl CoA not being able to enter matrix but for fats synthesis citrate is needed and citrate synthase make citrate in CAC and that cna cross membrane when CAC slow down due to having a lot of energy and that citrate is now in cytoplasm and gets broken down into acetyl CoA and also regenertae pyruvate which gets returned to mitochondria while acetyl CoA gets used for synthesis of fatty acyl chains
what are teh enzymes needed for acyl chains synthesis
acyl chain synthesis occur in cytoplasm which is where acetyl CoA is and the enzmyes needed are acetyl CoA carboxylase and Fatty Acid Synthase
acetyl CoA carboxylase is responsibvle for convertinf Acetyl CoA to malonyl CoA which is activated 2C carrying precuror for fatty acid synthesis and this enzyme is commited and regulated step for fatty acid synthesis and it uses ATP
Fatty Acid synthase use NADH as reducing power