1. Double membrane structure of the mitochondrion:(fig. 12-6a, Lodish) (fig. 12-6b, Lodish)

2. The citric acid cycle. Look (fig. 12-8, Lodish) to see an overview of how the citric acid cycle (TCA cycle) fits in to glucose metabolism

• The pyruvate dehydrogenase complex breaks the three carbon pyruvate into carbon dioxide and a two carbon acetyl fragment, which enters the citric acid cycle. A detailed view of this process is given in this figure by your instructor. A deficiency in thiamine results in the disease "beriberi". Thiamine, also known as vitamin B1 and described by Casimer Funk as the first "vitamine" (amine required for life), is found in meat, yeast, unpolished cereal grains (with the outside coating intact), enriched grain, and breakfast cereals. Symptoms of beriberi include weight loss, emotional disturbance, weakness, and heart irregularities. Beriberi is known mostly from developing countries, where polished rice is a major component of diet, and among alcoholics, who have impaired liver function. Recovery can be dramatically fast, sometimes within an hour of a thiamine pyrophosphate injection.
• The two carbon acetyl fragment is added to a four carbon oxaloacetate to make a six carbon citrate (citric acid). As citrate is broken down to oxaloacetate, two carbon dioxides are lost, and NADH, FADH₂, and GTP are produced. (fig. 12-10, Lodish) is a synopsis of this process.
• NADH and FADH₂ are reduced molecules which carry the energy conserved into the electron transport chain, where the energy is used to make ATP from ADP and phosphate.
• NADH has enough energy to make 3 ATP molecules from ADP and FADH₂ has enough energy to make 2 ATP molecules.
• Pyruvate can easily enter the mitochondria. But, NADH cannot! If the mitochondrial membranes were freely permeable to NADH, NADH produced in the mitochondrion would be able to move out into the cytoplasm instead of being confined to the mitochondrion where it could transfer energy to the electron transport chain. So, a shuttle is used. The shuttle transfers the energy associated with the NADH without actually transfering the NADH itself. In liver, kidney and heart mitochondria, this takes place by the malate-aspartate shuttle. (Another view of this is given by fig. 12-11, Lodish.)
  

  In skeletal muscle and brain, the glycerol-phosphate shuttle is used. The glycerol-phosphate shuttle releases FADH₂ inside the mitochondrion instead of NADH. Why? Well, in the cells where the glycerol-phosphate shuttle is primarily used, NADH concentrations are lower in the cytosol than in the mitochondrion. It takes energy to move a substance from a lower to a higher concentration. The reducing power of NADH, which is worth 3 ATP's, winds up as FADH₂ which is worth only 2 ATP's. The lost ATP provides the energy to move the reducing power into the mitochondrion.

• (New) Fatty acids (hydrophobic tail regions from phospholipids and some other related lipids) enter the citric acid cycle by breakdown of the fatty acid chains into two carbon acetyl fragments by beta-oxidation. Fatty acids can't move across the mitochondrial membranes. So, there is a priming reaction, attaching the fatty acid to Coenzyme A. The fatty acid and CoA move through special channels into the matrix of the mitochondrion. Beta oxidation indicates that oxidation occurs at the number 3 (beta) position on the fatty acid chain.

  (New) Many lipids found in plants and animals have odd numbers of carbons. In this case, the end product is propionyl-CoA, which has three carbons, and is changed to succinyl-CoA to enter the TCA cycle.

All text and images, not attributed to others, including course examinations and sample questions, are Copyright, 2009, Thomas J. Herbert and may not be used for any commercial purpose without the express written permission of Thomas J. Herbert.