Carnitine article Carnitine spares glycogen. Why? Because if you have more Carnitine you will have more fatty acid oxidation for energy rather than using muscle stored glycogen. This enhances performance because it will allow you to go a little extra before using glycogen storesCholesterol Cont’d [Slide 7] We went through the first stage of cholesterol and now we will talk about its regulation Feedback imbibition will be the first thing that we look at. Meaning that if you have increased Cholesterol and bile acid levels you will decrease activity of HMG CoA Reductase. It is NOT allosteric! HMG CoA Reductase is active without a phosphate meaning that it will be favored by Insulin. It is inhibited by glucagon and with a phosphate. HMG CoA Reductase is regulated also at transcription levels. In our body we have Sterol Regulatory Element Binding Protein (SREBP) which is a transcription factor that will regulate other genes and transcription factors of cholesterol synthesis. So if you have too much of Cholesterol and bike acids, that will inhibit HMG CoA Reductase through activating this transcription factor, SREBP. So how can we lower the levels of Cholesterol in our bodies? We have already mentioned Statins such as Lovastatin; which target HMG CoA Reductase to inhibit its activity and synthesis at the transcription level by activating SREBP. That is one way. Another thing you can do to decrease Cholesterol levels is actually increasing fiber in diet. So how would that lead to a decrease in cholesterol levels? Fiber adsorbs bile acids. Those bile acids are going to be excreted rather than reabsorbed in the Ilium which usually 97-98% do. So increasing the excretion of fiber you get more synthesis of Cholesterol and bile. If you are not reabsorbing the bile through enterohepatic circulation it means you need to synthesize more which needs Cholesterol. This would increase Cholesterol in body but serum cholesterol itself does not increase. This is because the Cholesterol that is synthesized is being incorporated in bile and not sent to bloodstream so you have a net decrease in cholesterol. Another thing they are using a lot is Nicotinic acid and Fibrates which decrease the secretion of lipoproteins (LDL and VLDL) from liver which decreases TG and Cholesterol in serum. Cholesterol is going to be degraded in the feces as unabsorbed Cholesterol and neutral sterols which will mainly be converted to bile acids Now we have finished Cholesterol and will start bile acids. Synthesized in liver from Cholesterol and the synthesis of bile acids will happen in cytosol, SER, mitochondria and peroxisome. The first part (synthesis) will happen inside and adjacent to SER. The conjugation of the bile will happen in peroxisome. Major controlling enzyme is 7α-hydroxylase which introduces an –OH to the bile acid. Synthesis regulated by bile acids is returned to liver form intestine. Bile acids may be conjugated with Glycine or Taurine. Primary bile acids will go through hydroxylation and then conjugation. Hydroxylation will happen in a few different places because the two primary bile acids can have two different carbons but the first one is introduced by 7α-hydroxylase. Once we have the bile acids formed we are going to have to conjugate them with two different amino acids; Taurine or Glycine. Primary bile acids are Cholic Acid and Chenodeoxycholic acid and are the only two that are synthesized in the liver. Once they are synthesized they are part of the bile which is released into the intestine for the aid of digestion by emulsifying fat into smaller droplets. Most bile is reabsorbed but some will pass through to the colon. In colon we have bacterium which acts on the bile acids and converts them to secondary bile acids. Secondary bile acids are formed by a de-conjugation followed by a de-hydroxylation of a primary bile acid. Deoxycholic acid is formed from Cholic acid and Lithocholic acid is formed from Chenodeoxycholic acid. The secondary bile acids are the one that can actually be carcinogens (increased risk of cancer) because it tends to stay a little longer before excretion. This is why fiber is important; so it can bind to bile acid and excrete what was not reabsorbed. She said 97-98% will be reabsorbed in the Ilium but that is only for first three. Lithocholic acid is always excreted.Amino Acid and Protein Metabolism in Specific Tissues Once we have exogenous dietary proteins and endogenous body proteins they are all going to be broken down into amino acids which are our body’s building blocks. Those will be used for anabolism (synthesis of other substances). We can anabolize biogenic amines (synthesized from protein; nitrogen containing compounds that are frequently used in signaling in our body-acetylcholine, catecholamines, histamine and serotonin), hormones, plasma proteins, structural proteins, enzymes, immunoproteins and transport proteins You have your α carbon, your amine, carboxyl group and your R side chain which will be the one that differs between amino acids [slide 8]Here you see Alanine which has all the same things that Pyruvate does except that Alanine has an amine (-NH2) while Pyruvate (your α-keto acid) has a C=O [slide 6]α-AA1 + α keto acid2 α keto acid 1 + α-AA2 {So pretty much what will happen is the AA will bind to α- keto acid and form a second AA and a second α-keto acid. This uses an aminotransferase to transfer the amine group from AA1 to α-keto acid2 forming α-keto acid1 and AA2. That means that the AA that donated the amine group will become an α-keto acid and the α-keto acid that received the amine group became an AA. The same enzyme is always used; Aminotransferases or Transaminases. These require vitamin B6 in the form of PLP (pyridyl phosphate)} [slide4] Here we have a slide of essential amino acids. All the top ones are branching. Then we have the conditionally essential amino acids. Why are they called this? Because we synthesize nonessential. Once you have essential in body you can synthesize nonessential form essential. So if you are not getting the essential such as Phenylalanine, you wouldn’t be able to synthesize Tyrosine. Tyrosine would become conditionally essential because then you need to make sure you are getting that from your diet. That can be from lack of an AA in your diet. There is actually a problem with Phenylalanine. Some people can’t metabolize it. They still are getting it in
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