Biochemistry I Fall Term, 2000

Lecture 35: Integrated Metabolism

Assigned reading in Campbell: Chapter 20.1-20.4

Take the Review Quiz on Lecture 35 concepts.

Protein Kinase/Phosphatase Cascades: Handout on epinephrine and cAMP regulatory effects.
Protein Kinase/Phosphatase Cascades (PDF)

Nutrition

• Macronutrients: balanced intake is important, e.g. amino acid composition of diverse food sources.
• Micronutrients: vitamins and minerals are required in small amounts as coenzymes and cofactors (Table 20.3).
• Tables of DV's (RDA's) are only guidelines.
  The human population is genetically and metabolically diverse.
• Update: Leptin (p. 697) was shown recently to be counterproductive in controlling human obesity.

Hormones (acting in carbohydrate metabolism)

• Hormones maintain homeostasis in an organism and effect communication between different and distant organs and tissues.
• Hormones act by binding to specific receptors on (or within) target cells.
• Receptor binding causes the synthesis of an intracellular second messenger, e.g. cAMP.
• cAMP activates protein kinase(s).

The following material is an overview of insulin, glucagon, and epinephrine action on glycogen synthesis and breakdown. It is repeated from the Lecture 31 notes. (See also Campbell Figs. 20.7 and 20.8)

Hormonal Regulation of Protein Kinases and Protein Phosphatases.

Steps in the activation of glycogen phosphorylase

• Glucagon and/or epineprine bind to receptors on the surface of liver and muscle cells.
• The receptor-ligand (ligand=glucagon, epineprine) complex activates adenyl cyclase.
• Adenyl cyclase converts ATP to cAMP (cyclic AMP = 3',5'- cyclic AMP).
  
  cAMP is called a "second messenger".
• cAMP activates protein kinase A.
• Protein kinase A phosphorylates:
  1. phosphorylase kinase (activating kinase activity).
  2. glycogen synthase (inactivating it).
• Phosphorylase kinase phosphorylates glycogen phosphorylase, activating it.
• Phosphoprotein phosphatase (which would remove phosphates) is also phosphorylated to inactivate it.

Steps in the activation of Glycogen Synthase

To reverse the above effects we need to dephosphorylate the proteins that were phosphorylated in the above reactions. This occurs by activation of phosphoprotein phosphatase. This enzyme removes phosphate groups from proteins.

During glycogen degradation, phosphoprotein phosphatase is inactive because:

1. It is not phosphorylated on the correct location.
2. It is complexed with glycogen phosphorylase.

1. Phosphorylation by insulin-stimulated protein kinase activates it.
2. Binding of glucose to glycogen phosphorylase releases phosphoprotein phosphatase.

Once activated phosphoprotein phosphatase does the following:

1. Removes the phosphate group from glycogen phosphorylase, inactivating it
2. Removes phosphate group from phosphorylase kinase, inactivating it
3. Removes phosphate group for glycogen synthase, activating it

cAMP is hydrolyzed to AMP by a specific phosphodiesterase. The destruction of the "messenger" is necessary to reset the system to its normal metabolic state and to make it responsive to the next set of homonal signals. Two classic stimulants:

found in coffee (caffeine) and tea (theophylline) inhibit the phosphodiesterase. Other things being equal, this keeps cAMP levels higher than normal and accounts for some of the effects of these "uncontrolled drugs".

Return to Home Page.