Sunday, June 10, 2012

Biological Science 1 (Molecular Biology: Enzymes and Metabolism)


Day 1: 


A. Enzyme Structure and Function (Main Idea)
From memory: Enzymes are proteins that have a unique shape which creates an active site (where two different molecules can fit into). Placing two molecules close together on an enzyme increases the chance of the molecules reacting, thereby facilitating the reaction. Like a lump of clay that has a depression for two specific Lego pieces to align next to each other, then the whole lump can be squished assembling the Lego pieces...

1. Function of Enzymes in Catalyzing Biological Reactions
From memory: Catalysts always increase the rate of reactions, without being used in the reaction. For example heat is a catalyst to kool-aid production, since it is not used by the reaction (as are sugar, water and kool-aid powder) and it increases the rate of reaction (more kool-aid is made on hot days). An enzyme would be a catalyst, the way an abandoned building in a major city is a catalyst for HIV transfer between homeless people. The building provides a place for  HIV infected, homeless drug users and non-HIV infected, homeless drug users to collect near each other thereby facilitating the transfer due to close physical proximity of all the reaction components...

From online study: Structure determines function. Ex. if the abandoned building changes to a bank then it stops functioning to catalyze spread of HIV and starts to catalyze small business growth in the surrounding area.

From online study: Reactions that are catalyzed by enzymes include: Metabolism (use of energy), making RNA, DNA and protein, digestion. 

2. Reduction of Activation Energy
For the reaction:
chips (starch) + saliva -> sugar + obesity

Ea (activation energy) with a catalyst will be smaller then Ea with no catalyst.

The transition state (the highest energy peak) is lowered by using a catalyst.

Enzymes increase the rate constant, k: 

      equation rate = k[A][B]
      equation rate = k[water][sugar][kool-aid powder]
      equation rate = k[HIV infected drug users][non-infected drug users][needle & drug]
      equation rate = k[chips][saliva]

k depends on temperature, ionic strength, surface area and light irradiation. 

Keq is not changed by enzymes, because enzymes increase the rate (lowers the Ea) of the forward and reverse direction of a reaction.

Keq = equilibrium constant

Enzymes affect the kinetics (motion) of a reaction, but not the thermodynamics (heat). Therefore ΔG (total change of energy) is not affected.

3. Substrates and Enzyme Specificity
Enzymes only fit specific substrate into their active site. Enzymes usually distinguish between stereoisomers like fake sugar vs natural sugar. 

Enzymes can be protein (most enzymes) or RNA (ribosome)
      Primary Level - sequence of protein or 
                                       RNA chain
      Secondary Level - alpha helices and beta sheets caused by hydrogen bonding, 
                                       base pairing for RNA
      Tertiary Level - 3D structure caused by R Groups interactions and spacial arrangement  
                                        of secondary structure
      Quaternary Level - Multiple chain interaction (like hemoglobin)

Heat and extreme pH denatures enzymes breaking the tertiary and secondary structure.


B. Control of Enzyme Activity
Enzymes control many natural effects on the human body, helping to digest particular food types, helping the body repair itself, helping the body regulate a constant internal environment.

1. Feedback Inhibition

The product of a reaction signals there is enough product and prevents more from being made. 

Ex. hexokinase (the first enzyme in glycolysis) is inhibited by its product glucose-6-phoshate


2. Competitive Inhibition
The active site of the enzyme can be blocked with something else (inhibitor) causing less enzymes to be available at one time and less product to be made, unless competitive inhibition is overcome by using a ton of the desired substrate to out compete the competitor.   

The maximum rate of the enzyme's catalysis does not change in competitive inhibition. 

The active site is where the inhibitor binds in competitive inhibition.


3. Noncompetitive Inhibition
The enzyme is deactivated by an inhibitor binding to an allosteric site.

The maximum rate of the enzyme's catalysis is changed in noncompetitive inhibition.

Substrate levels have no effect on the rate during noncompetitive inhibition.


C. Basic Metabolism
The usage of energy at every level of a living organism. Energy can be stored up like starch from photosynthesis, or broken down like glycolysis in animals.

Catabolism: consume energy 

Anabolism: store energy (like adipose/fat tissue)

Cellular Respiration: Metabolism C6H12O6 + 6O2 => 6CO2 + 6H2O

Aerobic Metabolism (glucose oxidizes to carbon dioxide produces 36 ATP/1 glucose)
  •       Glycolysis (2 pyruvate, 2 net ATP, 2 NADH)

  •       Oxidative Decarboxylation (convert pyruvate to acetyl group which attaches to coEnzyme A, makes 2 NADH/1 glucose *1NADH/1 pyruvate*)

  •       Krebs Cycle (produces COwith the  O2 and C from glucose)
  •       Electron Transport Chain (produces water with the  O2 from breathing, harnesses                      -    the energy of oxygen breaking down to molecular form)

Anaerobic Metabolism (partial oxidation of glucose to pyruvate produces 2 ATP)
  •       Glycolysis (2 pyruvate, 2 net ATP, 2 NADH)
  •       Fermentation of Alcohol or Lactic Acid (pyruvate reduced to ethanol/bacteria or    -   -    lactate/human, NADH is oxidized)


1. Glycolysis (Anaerobic and Aerobic, Substrates and Products)
The first step in both anaerobic and aerobic respiration, takes place in the cytosol. Inhibited by ATP.

  • Anaerobic (regenerate NAD+ needed for glycolysis)

Substrate: Glucose C6H12O6
Products: 2 Pyruvate, 2 net ATP, 2 NADH -> 2 Lactate or 2 Ethanol, 2 NAD+/1 glucose
                                                                               *1 Lactate or 1 Ethanol, 1 NAD+/1 pyruvate*

  • Aerobic

Substrate: Glucose C6H12O6
Products: 2 Pyruvate, 2 net ATP, 2 NADH -> 2 Acetyl CoA, 2 NADH/1 glucose
                                                                               *1 Acetyl CoA, 1 NADH/1 pyruvate*


2. Krebs Cycle (Substrates and Products, General Features of the Pathway)
The Krebs Cycle is also called the citric acid cycle or Tricarboxylic Acid Cycle. The Krebs Cycle drives the Electron Transport Chain where most of the ATP is produced. Acetyl CoA enters the matrix of the mitochondria. Inhibited by ATP and NADH. Coenzyme A is regenerated in the first step of the cycle.

Each glucose produces: 4CO2,  6NADH, 2 FADH2 and 2ATP. 
Each cycle produces: 2CO2,  3NADH, 1 FADH2 and 1ATP. 


3. Electron Transport Chain and Oxidative Phosphorylation (Substrates and Products, General Features of the Pathway)
NADH from the Krebs Cycle enters the cristae of the mitochondria. A series of redox reactions oxidizes NADH to NAD+ and O2 gets reduced to H2O

The electrons move from NADH to FMN, to Coenzyme Q, iron-sulfur complexes, and cytochromes (b, c and aa3) then reduce oxygen.

NADH is the highest energy, Ois the lowest energy, therefore energy is released as electrons are passed on down the series of proteins to O2.

FADH (having lower energy then NADH) skips FMN and passes electrons to Coenzyme Q.

Oxidative Phosphorylation refers to a proton gradient (caused by the release of energy as the electrons move) which drives ATP synthase to make ATP. 

Proton Gradient: energy released by the electrons moving pumps protons into the intermembrane space of the mitochondria (H+ is very high there), in order to return to a lower concentration in the matrix the H+ must pass through ATP synthase, which harnesses the energy of the protons like a watermill to convert ADP into ATP.

Antibiotics, cyanide, azide and CO inhibit the Electron Transport Chain.


4. Metabolism of Fats and Proteins
Fat is broken down when easier food is not available to the body. It can be broken down by the liver. By weight fat has the most energy of any food type.

Beta-oxidation (the break down of fatty-CoA to make acetyl CoA, FADH2 and NADH) occurs in the matrix of the mitochondria.  Acetyl CoA feeds the Kreb Cycle, FADH2 and NAD feed the Electron Transport Chain.

Fatty esters are hydrolyzed into free fatty acids by lipase in the cytosol. 

Ex. Triglycerol hydrolyzes into free fatty acids and glycerol.

Fatty Acids use ATP to become a thioester.

Protein is usually not broken down for energy (an exception is starvation).

Proteins are broken down by peptidases into amino acids. The nitrogen is converted to urea. The carbon is converted to pyruvate, acetyl CoA, oxaloacetate or other intermediates depending on amino acid. The carbon products either feed the Krebs cycle or go through gluconeogenesis. 


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