B.4 Metabolic Pathways

Many enzymatic reactions are part of larger metabolic pathways.
o In these sequential reactions, the substrate of one step is the product of the previous one and is therefore, a modification of the previous substrate.
o Because each reaction is different, each one requires a different enzyme.

• -  This consecutive nature of the reactions in metabolic pathways allows the energy and electron shifts to occur in small steps having negligible impacts on other aspects of metabolism.

• This control is vital to homeostasis.
  o Two well-known examples of metabolic path ways are cellular respiration

  , which occurs in almost every cell, and photosynthesis , which only occurs in cells that contain chlorophyll.

• -  The significance of cellular respiration cannot be overstated. This is the process by which cells break down food molecules and store available chemical bond energy in molecules of ATP.

  o ATP is subsequently “harvested” to supply energy for cellular needs, such as endothermic reactions, cell division, movement and so on.

  o Cellular respiration is often referred to as carbohydrate metabolism because cells usually utilize sugars as a starting point for these reactions but, when sugars are not available, cells are able to metabolize lipids and proteins to generate ATP using different metabolic pathways.

• The set of reactions that takes place in cells, allowing them to use sugar as an energy source, is called glycolysis.

o This complex metabolic process occurs in both prokaryotic and eukaryotic cells, under aerobic and anaerobic conditions.

o Although cells have the ability to utilize various sugars for energy, glucose, the most abundant one, is usually considered the initial substrate in glycolysis.

Glycolysis

These hexose (6-carbon sugar molecules) must first be energized.
o During these phosphorylation steps, glucose is converted into fructose and two molecules of ATP are used to add two phosphate groups to it.
o The resulting molecule is fructose1,6-diphosphate.
o Phosphorylation is an energy “cost” to a cell. The ADP molecules that are produced

from the process are available to synthesize ATP when the energy and inorganic

phosphate are available.

• -  The phosphorylated sugar is then cleaved into two parts to produce two three-carbon molecules, each of which is still energized by the presence of a phosphate group.

• -  Finally each of these three-carbon units is converted into pyruvate (PYR; ionized form of pyruvic acid).

• -  One hexose will generate two PYR molecules.

These last reactions result in the production of four molecules of ATP.

• -  Glycolysis is often summarized in three steps:

  o Phosphorylation o SugarCleavage o PYRformation

• -  Regardless of the type of cell and the conditions under which the reactions are occurring, these processes are always the same.

• -  Given that cells have to spend two ATP during phosphorylation, by the end of glycolysis there is a net production of two molecules of ATP.

• -  For cells that are not very active such as prokaryotic cells, this is enough to satisfy their energy requirements.

• -  In eukaryotic cells, which are more active, the production of only two molecules of ATP from each sugar molecule is not generally life-sustaining.

• PYR, the final product of glycolysis, is a hydrocarbon that is still rich with chemical bond energy.

o Most eukaryotic cells are aerobic and they conduct further metabolic pathways known as Krebs cycle and the electron transport chain (ETC) to harvest his energy.

o These reactions occur in the mitochondria and require the presence of oxygen.

• -  In these cells, given that oxygen is available, each three-carbon pyruvate (PYR) is converted into acetate (a two-carbon ionic form of acetic acid).

• -  To accomplish this, both a carbon and hydrogen atom are removed from PYR by the enzyme pyruvic acid dehydrogenase (PAD).

  The released carbon forms the low energy metabolic waste CO2 where the high energy hydrogen atoms bond onto the coenzyme NAD forming NADH2.

• -  The remaining 2-carbon acetyl group is transported into the mitochondria by the action of coenzyme A where it is combined with oxaloacetate (4 carbons) to form citric acid (6 carbons).

o Citric acid gets partially disassembled releasing two molecules of CO2 as well as hydrogen atoms that bond to H-carriers like NAD.

o The other product of these degradation steps of Krebs cycle is oxaloacetate, which can gain another 2-carbon acetyl group.

• Other molecular complexes in the mitochondria receive the hydrogen atoms from the hydrogen carriers and pass them along the electron transport chain.

• -  This series of reactions uses oxygen as the eventual hydrogen acceptor, which generates water molecules as the hydrogen atoms are returned to a (normal) low energy level.

• -  The energy released from the breakdown of the carbohydrate is used to add P to ADP to produce ATP.

• -  Seventeen molecules of ATP are generated from each two-carbon molecule that enters the mitochondria to be metabolized by Krebs Cycle.

  The end result of the complete aerobic respiration of one glucose molecule is the net production of 36 molecules of ATP, 6 molecules of CO2, and 6 molecules of H2O.

  Fermentation

  - If oxygen is not available as a final hydrogen acceptor in aerobic cells, the electron transport chain is unable to produce water, the H-carriers do not release hydrogen and Krebs Cycle comes to a halt.

  o In these cases, the alternative pathways called fermentation follow the formation of PYR.

  In plants

  o Fermentation is different in plant and animal cells because of the presence of different enzymes.

  § In plant cells, PYR is metabolized into ethanol ,a two-carbon alcohol. This two-step process is irreversible because of the loss of a carbon atom and the formation of CO2. If oxygen is subsequently available, ethanol is converted into acetic acid (vinegar), also a two-carbon molecule.

  In animals

• In active animal cells, such as muscle cells, a lack of oxygen means that PYR will accumulate faster than the available oxygen allows it to be converted to acetate.

  o Animal cells produce lactic acid dehydrogenase (LAD).
  o This enzyme catalyzes the conversion of excess PYR into lactate by adding hydrogen to it.
  o A build-up of lactic acid causes sore and stiff muscles. Lactic acid is a three-carbon molecule; no carbon dioxide is released during its production.
  o When oxygen becomes available, LAD removes hydrogen from lactic acid,

  converting it back into PYR; the soreness and stiffness in muscle tissue goes away.

• o The hydrogen atoms combine with oxygen to form water. The PYR that is

  reconstituted is used to generate acetyl molecules for further metabolism by Krebs Cycle and the electron transport chain in the mitochondria.