Friday, November 27, 2015

Biology: Metabolism (Biochemistry)


Carbohydrates are stored primarily in the muscle and liver as glycogen. This process is called glycogenesis. Taking carbohydrates out of storage to be broken down for energy is called glycogenolysis.

Lipids, on the other hand, go through much of the same process. Triglycerides are mainly stored in adipocytes. The chemical breakdown of a FA is called beta-oxidation.

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Glycolysis: - The breakdown of glucose into pyruvate (3C molecule).

  • It's an anaerobic metabolic pathway 
  • Occurs in the the cytosol 
  • The production of ATP by the transfer of phosphate to and ADP, as in glycolysis, is caled substrate-level phosphorylation.
  • It's a ten step process




    Steps 1, 3, and 10 have a negative Gibbs Free Energy which means these steps are spontaneous, and likely irreversible. This is important for gluconeogenesis.

    Fermentation describes metabolism in the absence of oxygen, which includes glycolysis as well as the reduction of pyruvate to ethanol or lactic acid and the oxidation of NADH back to NAD+.
         -Yeast produce ethanol in fermentation, while human muscle cells produce lactic acid.

    The Pentose Phosphate Pathway (PPP) is an alternative pathway to glycolysis. Its purpose is to create NADPH and some five carbon sugars, including ribose. The whole pathway is regulated solely by NADPH, which inhibits the first step. Two parts of the pathway include:

    • Oxidative branch - Generates NADPH
    • Non-oxidative branch - Creates important five carbon sugars like ribose for nucleotides.



    Since these reactions are all governed by enzymes, a typical question would ask what happens when a certain enzyme is inhibited by a poison. The poison will create a buildup of reactants and a dramatic reduction of products of the reaction that the enzyme governs. Mutations that lead to non-functional enzymes would produce similar results.

    Another typical question would ask the speed of reaction in glycolysis. Insulin would speed up the reaction, and glucagon would slow it down.

    Gluconeogenesis is the process of synthesizing glucose from non-carbohydrate products, such as proteins and lactic acid, a process done by the liver.
          -To be a substrate for gluconeogenesis, the molecule must have a 3-carbon backbone. (glycerol, lactic acid, etc.)

    -The primary substrate for glycogenesis is glucose 6-phosphate (G6P), which is also the product of the first step of glycolysis. Glycogen synthesis uses one UTP, which is a triphosphate nucleotide that is energetically equivalent to ATP. Moreover, glycogenolysis does NOT require ATP.

    In general, insulin promotes glycolysis and glycogenesis (decrease blood glucose). Glucagon promotes gluconeogenesis and glycogenolysis (increased blood glucose).

    All these pathways - glycolysis, gluconeogenesis, glycogenesis, and glycogenolysis - intersect at a molecule called glucose 6-phosphate (G6P)

    Unsaturated fats store less energy, and because they have two fewer electrons for every double bond present, their reducing potential is decreased.
         -After beta-oxidation of FA's, they can be converted to ketone bodies in a process called ketogenesis. It is called beta oxidation because it is oxidized 2 carbons at a time. It takes place in the mitochondria of liver cells.

    Lipoproteins are produced primarily in the liver, intestines, and adipocytes, and are expelled via exocytosis. The intestines, in particular, produce a special type of lipoprotein called a chylomicron.
         -LDL brings lipids from the liver to the periphery.
         -HDL brings lipids from the periphery to the liver.


    Regulation of Metabolism:

    • Blood glucose only can come from the intestines or the liver. 
    • Red blood cells and the brain always require glucose. 

    Insulin is released from the pancreas in response to increased blood glucose levels and promotes glycolysis in all tissues, glycogenesis in the liver and muscle, and fatty acid synthesis in the liver, and fatty acid storage in adipocytes.

    Glucagon is released from the pancreas in response to decreased blood glucose levels and promotes glycogenolysis in the liver and muscle, gluconeogenesis in the liver, fatty acid release in adipocytes, and beta-oxidation in almost all tissues.

    In late starvation, the absence of insulin promotes ketogenesis.
    In order for ketogenesis to happen, there must be an absence of insulin, and the abundance of acetyl-CoA. The absence of insulin is permissive, while the abundance of acetyl-CoA is what truly allows ketogenesis to happen.

    Epinephrine promotes glycogenolysis and the removal of glucose from storage.
    Cortisol promotes gluconeogenesis.

    Hormones control metabolic enzymes in the same ways that all enzymes are controlled:

    1. Phosphorylation
    2. Regulation of the synthesis of enzymes
    3. Use of control enzymes
    4. Local metabolic effects
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    ATP contains phosphoanhydride bonds, or phosphoric acids that are linked at an oxygen atom. Hydrolysis of these bonds is spontaneous and exothermic, often providing the energy needed to overcome less energetically favorable reactions. 


    Oxidative phosphorylation occurs when oxidation reactions provide the energy for phosphorylation. (Usually phosphorylation for the production of ADP --> ATP)

    The energy to run oxidative phosphorylation comes from NADH, which is the reduced form of nicotinamide adenin dinucleotide (NAD+)

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    Most NADH production comes from the CAC, which takes place in the mitochondrial matrix.
         -The outer membrane is permeable to small molecules, and NADH and pyruvate make it through.
         -The inner membrane however, is less permeable. Although pyruvate, FAs and ketone bodies can make it through, hydrolysis of ATP is usually required to transport each NADH.

    -The carbons lost as CO2 in the CAC is through decarboxylation reactions.


    The CAC is considered to be an aerobic reaction.

    NADH provides a source of regulation. If NADH builds up, the CAC slows down.
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    The Electron Transport Chain (ETC) is a series of proteins that carries electrons from NADH to O2. These proteins include ubiquinon and cytochromes, which are intermediate electron carriers in the ETC.
         -Oxygen is a key regulator of the ETC. When it is present, the ETC runs as described above. When it is absent, there is no acceptor to which the final electron carrier of the chain can pass its electrons. This eventually even slows down the CAC, and the excess NADH as a result of lack of oxygen shifts the cell into anaerobic fermentation, so NADH is converted to NAD+ by the conversion of pyruvate to lactate.
























    The intermembrane space has a lower pH than the matrix, due to the buildup of protons.

    Net products and reactants for respiration:
    Glucose + O2 --> CO2 + H2O (Not a balanced reaction, this is a combustion reaction)
         -The oxygen one breathes in does not become CO2, although it is exchanged for CO2. Instead, it becomes H2O.


    Net ATP:




























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