|Lecture Notes:: 26 September||
Let's start with a brief overview of the names, structures and physiological functions of the common vitamins as shown on the overhead and discussed in Chapter 18, Special Focus beginning on p 586 in G&G: Niacin, Riboflavin [B2], Thiamine, Pantothenic acid, Biotin, Pyridoxal [B6], Folic acid, Lipoic acid, Cobalamin [B12], L-Ascorbic acid [C], and the lipid soluble vitamins A, D, E, and K). Fun facts:
Vitamins giving "ADP" containing coenzymes:
NAD+: Note that we have the active group, nicotinamide, attached to a recognition group "ADP" (in bold). This is the major redox coenzyme in organisms. It participates in oxidation by picking up a Hydride ion on the number 3 carbon. The ADP portion seems to function with the adenine ring portion binding to the protein and holding the nicotinamide so that it is properly positioned for catalysis. This appears to be a common theme among coenzymes which we will see again. Substituting a phosphate for the 2' hydroxyl gives NADP+, the redox cofactor used in biosynthetic pathways.
Riboflavin (Vitamin B2):
Catabolism: degradation of molecules to provide energy.
Anabolism: reactions using energy to synthesize new molecules for growth etc.
Metabolic Pathways: (overhead - Interactions of Metabolic Pathways) sequences of consecutive enzyme catalysed reactions which are readily studied and traced. A more rational definition is that of Newsholme and Leach (Biochemistry for the Medical Sciences, Wiley, 1983: pg.42) "[A] metabolic pathway is a series of enzyme-catalyzed reactions, initiated by a flux-generating step and ending with either the loss of products to the environment, to a stored product (a metabolic 'sink') or in a reaction that precedes another flux-generating step (that is, the beginning of the next pathway)." Where a flux generating step is a non-equilibrium reaction that generates the flux going through the pathway and to whose rate all other reactions of the pathway conform. Note that by this definition some pathways may be inter-organ while others may take place in single compartment. We will explore this definition/concept as we look at metabolism.
Characteristics of pathways:
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" and we will focus on it in our study.
The Stages of Catabolism [overhead]: For convenience we can breakdown catabolism into four hierarchical levels:
Metabolism would be extremely complex if coupled processes directly, however. Instead use an intermediate energy carrier: ATP. Thus catabolic processes make ATP which can then be used for anabolic processes, locomotion, pumping ions across cell membranes (major contribution to basal metabolic rate or BMR), etc. Note that ATP is not used to store energy however. (Often compared to electricity's role in our culture).
ATP is sometimes referred to as a "Hi Energy" compound. High energy in this case does not refer to total energy in compound, rather just to energy of hydrolysis. Thus ATP is unstable to hydrolysis, or has a large negative DG for hydrolysis. For biochemistry High Energy is defined in terms of ATP: if a compound's free energy for hydrolysis is equal to or greater than ATP's then it is "High Energy," if its free energy of hydrolysis is less than ATP's then it is not a "hi energy" compound. Note that ATP has two hi energy anhydride bonds. Catabolic pathways are designed to create "hi energy" compounds which can be used to make ATP from ADP, or which make "fuel" for the electron transport system, which in turn makes ATP from ADP. The "hi energy" in ATP is then used in biosynthesis and especially to to drive mechnical processes (such as pumping ions across membranes or moving proteins relative to each other as in muscle contraction) as it is converted back to ADP.
Look at ATP. In the figure the bolded region is the "recognition" part of the molecule, while the polyphosphate is the chemically active portion. Each of the phosphoric acid anhydride bonds is "hi-energy." That is hydrolyzing either will release a lot of energy.
So why ATP? First, we want a compound with intermediate hydrolysis energy so it can pick up energy from some reactions and deliver to others. Second we want a kinetically stable molecule which is thermodynamically unstable. Thus acetic acid anhydride would not work: it is thermodynamically unstable to hydrolysis, but it is also kinetically unstable, with the carbonyl carbons wide open to water attack. Phosphoric acid anhydride is equally unstable, but is is sterically protected from water attack - in order to react quickly we need a catalyst - perfect.
. Before we begin looking at cells and specific metabolic pathways, let's take a brief look at how glucose gets to the tissue from food intake as an example of digestion.