|Lecture Notes:: 8 October
© R. Paselk 2001
Catabolism: degradation of molecules to provide energy.
Anabolism: reactions using energy to synthesize new
molecules for growth etc.
Metabolic Pathways: (overhead/handout - Interactions
of Metabolic Pathways) sequences of consecutive enzyme catalysed
reactions which are readily studied and traced.
Characteristics of pathways:
- First committed step
- Localized in eukaryotes
- Catabolic and anabolic pathways are generally distinguished
by coenzymes and/or compartmentalization.
The flux through a metabolic pathway is invariably controlled
or regulated, most commonly by Feedback Inhibition,
but also through Feed-forward activation. Regulation is one of
the things that makes biochemistry "biological."
of Catabolism (overhead/handout): For convenience we can
breakdown catabolism into four hierarchical levels:
- Stage I Hydrolysis of polymers to monomeric units (fat->
fatty acids and glycerol, protein-> amino acids, etc.)
- Stage II breakdown of products of Stage I to pyruvate, acetyl
CoA, and/or intermediates of the Kreb's Cycle
- Stage III Breakdown of Acetyl CoA by the Kreb's Cycle into
carbon dioxide and water with the production of reducing equivalents
- Stage IV Oxidation of the reducing equivalents by oxygen
with the production of ATP via the Electron Transport System.
These stages are summarized in
For food taken into the body, digestion accomplishes Stage
I, as outlined below. (Breakdown of substances in cells etc. will
of course be done somewhat differently.)
- Initial, limited, breakdown of starch in mouth by salivary
- Low pH of stomach inactivates salivary amylase, denatures
many proteins etc.
- In duodenum digestive enzymes are added from the pancreas
(pancreatic amylase, lipases, proteases), pH is neutralized,
and detergents (bile acids) are added from gall bladder.
- Starches, Proteins, Lipids are all hydrolyzed in duodenum
and small intestine where monomers are absorbed across intestinal
epithelium. Amino acids and sugars are released into the portal
vein to travel to the liver and then the rest of the body.
- First pass through the liver removes sugars and most of the
amino acids for processing, storage and release of glucose and
fatty acids for use in the peripheral tissues.
Glycolysis is going to be our first pathway, and it
is arguably the most important and universal of the metabolic
First if we look at the Glycolysis
Pathway (overhead/handout), we can break it into three
- Phase 1: phosphorylation and rearrangement of glucose
to give a molecule that can be cleaved to two inter convertible
trioses: glucose to F-1,6-bis P (energy invested);
- Phase 2: oxidative phosphorylation of an aldehyde
to give a mixed acid anhydride with subsequent transfer of the
phosphate to ATP: DHAP & GA-3-P to 3-PGA (energy repaid);
- Phase 3: rearrangement of a phospho-ester to an
enol-phosphate with subsequent transfer of phosphate to ATP:
3-PGA to Pyruvate (energy profit). The resulting pyruvate
may now go on to the Kreb's TCA Cycle or be converted into lactate.
In either case it is critical to regenerate the NAD+
or Glycolysis will come to a halt.
- In order to provide glucose for vital
functions such as the metabolism of RBC's and the CNS during
periods of fasting (greater than about 8 hrs after food absorption
in humans), the body needs a way to synthesis glucose from precursors
such as pyruvate and amino acids. This process is referred to
as gluconeogenesis. It occurs in the liver and in kidney. Most
of Glycolysis can be used in this process since most glycolytic
enzymes are reversible. However three irreversible enzymes must
be bypassed in gluconeogenesis
vs. glycolysis (overhead/handout):
Hexokinase, Phosphofructokinase, and Pyruvate kinase. Phosphofructokinase,
and/or hexokinase must also be bypassed in converting other hexoses
Overview of Glucose Metabolism in the Tissues: Diagram
- Last modified 16 October 2001
- © R Paselk