Скачать или смотреть Amino acid and lipid metabolism: an overview, focusing on key points

Key points about amino acid metabolism:
• Amino acid metabolism involves:
1) The removal of amino groups (typically via transamination)
2) Breakdown and/or use of the carbon skeletons (which have different fates depending on the amino acid)
3) Disposal of amino groups as urea via the urea cycle in the liver

• Transamination:
o Transamination is the transfer of amino groups from one molecule to another and is the first step in most amino acid metabolism
o Various transaminases can remove amino groups from one amino acid (to produce an α-keto acid) and pass them to an α-keto acid to make a new amino acid
o These reactions are typically readily reversible
o Transamination reactions often use the cofactor pyridoxal phosphate (PLP)
o Often, amino groups are passed onto α-ketoglutarate to make glutamate
 Leaves carbon skeletons that may be able to join the TCA or other pathways
o Key amino acid -keto acid pairs:
 glutamate : α-ketoglutarate (TCA intermediate)
 aspartate : oxaloacetate (TCA intermediate)
• ASpartate Transaminase (AST)
 alanine : pyruvate (gluconeogenesis, oxidize to enter TCA, etc.)
• ALanine Transaminase (ALT)

• Carbon skeletons:
o Amino acids can be classified as glucogenic if their breakdown involves the production of pyruvate or TCA intermediates
 As such, they allow removal of oxaloacetate (technically malate which is then converted to oxaloacetate) to be used to make glucose without depleting TCA intermediates
o Amino acids can be classified as ketogenic if their breakdown involves the production of acetyl-CoA or acetoacetyl-CoA
 These can be used to make ketone bodies or lipids

• Urea cycle:
o To avoid ammonia build-up, amino groups are excreted as urea via the urea cycle, which takes place in the liver
o Amino groups to be disposed of are transported through the bloodstream to the liver as (typically) glutamine or alanine
 Glutamine is the main one used by tissues, expect for muscles
 The glucose-alanine cycle allows muscles to dispose of amino groups on alanine that gets shipped to the liver where the liver removes the amino group, leaving it with pyruvate that it makes into glucose that it sends back to the liver
o In the liver, the urea cycle takes amino groups from amino acids and converts them into urea, which the kidneys can excrete in the urine
o Involves an aspartate intermediate
o Key regulatory step: carbamoyl phosphate synthetase I (CPS-1)
 Activates ammonia (freed from glutamate) it for incorporation into urea
 Regulated indirectly through arginine levels (through the allosteric regulator N-acetylglutamate (NAG)

• Key points about lipid metabolism:
o Lipid synthesis and breakdown are inversely regulated
o All tissues need fatty acids for various purposes: use as fuel, incorporation into membranes, production of steroids, etc. But “only” liver cells (hepatocytes) & fat cells (adipocytes) can make fatty acids
o The liver & adipocytes make fatty acids, store them (as triacylglycerols (TAGs)), & ship them out to other tissues in need.
o These fatty acids have to be “mobilized” from triacylglycerols (TAG) stores by lipases
o Fatty acids are made from acetyl-CoA (2 carbon (2C)) and broken down to acetyl-CoA (and one propionyl-CoA (3C) per odd-chain fatty acid)
 Anabolism:
• Fatty acid synthesis occurs mostly* in the cytosol of liver & fat cells (*some in mitochondria)
o Key regulatory point: acetyl-CoA carboxylase (ACC), which activates acetyl-CoA for incorporation
o Key user of NADPH (which can be made through pentose phosphate pathway (PPP))
o Because acetyl-CoA can't get through the mitochondrial membranes, citrate, not acetyl-CoA, is removed from the mitochondria to make fats - it is subsequently broken down back to acetyl-CoA by ATP-citrate lyase
• Incorporation into more complex lipids occurs in the ER

More on metabolism: http://bit.ly/metabolismglycolysis & https://bit.ly/bbmetabolism
 
more about all sorts of things: #365DaysOfScience All (with topics listed) 👉 http://bit.ly/2OllAB0 or search blog: http://thebumblingbiochemist.com     
   
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