Humboldt State University ® Department of Chemistry

Richard A. Paselk

	VUB Biology	Fall 2001
Lecture Notes:: 8 October	© R. Paselk 2001

Metabolism

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:

• Irreversible
• First committed step
• Regulated
• 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."

The Stages 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 (NADH etc.)
• Stage IV Oxidation of the reducing equivalents by oxygen with the production of ATP via the Electron Transport System. These stages are summarized in

DIGESTION

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 amylase
• 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

Glycolysis is going to be our first pathway, and it is arguably the most important and universal of the metabolic pathways.

First if we look at the Glycolysis Pathway (overhead/handout), we can break it into three phases:

• 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.

GLUCONEOGENESIS

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 to glucose.

Overview of Glucose Metabolism in the Tissues: Diagram (overhead/handout)

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Notes

Last modified 16 October 2001

© R Paselk