Humboldt State University ® Department of Chemistry

Richard A. Paselk

Chem 438 - Introductory Biochemistry - Spring 2013

Lecture Notes:

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Metabolic Integration

Now we can look at what occurs in fasting. In Table 3, below, is some data on the varying concentrations of key fuels and insulin, the major metabolic regulatory hormone. Notice that glucose concentrations fall for a few days, but then stabilize at about 3.5 mM. Given that an average liver has about 100 g of glycogen, and that glucose usage in the fed state is about 9-10 g/hr an average man would run out of glucose in only ten hours if some other fuel source did not become available after feeding. In fact liver glycogen lasts for about 24 hours. So what's going on?

Table 3: Concentrations of Major Fuels During Starvation in Man
Substance 

Serum or plasma concentration (mM) 

 Days

Fed 1 2 3 4 5 6 7  28-42
Glucose 5.5 4.7 4.1 3.8 3.6 3.6 3.5 3.5  3.6
 Fatty acids 0.30 0.42 0.82 1.04 1.15 1.27 1.18 1.88  1.44
 Ketone bodies 0.01 0.03 0.55 2.15 2.89 3.64 3.98 5.34  7.32
Insulin* >40 15.2 9.2 8.0 7.7 8.6 7.7 8.3  6

 *Insulin concentration is expressed in greek mu or microU/mL

Data from E. A. Newsholme & A. R. Leach (1983) Biochemistry for the Medical Sciences, John Wiley, NY. pp 338 & 539.

Looking at fasting from 24 hours to 24 days or so, we see

So how are these changes initiated and controlled?

Glucose/Fatty acid control cycle (muscle): During carbohydrate stress (liver glycogen stores are depleted, so serum [glucose] falls) the utilization of glucose by muscle falls as fatty acids are metabolized.

Glucose/Ketone body/Fatty acid control cycle (peripheral tissues, i.e. brain, kidney, intestine): When at rest the non-muscle peripheral tissues generally consume more glucose than muscle. So how do they respond to carbohydrate stress?

Metabolism in Exercise

(This discussion is based largely on material from E. A. Newsholme & A. R. Leach (1983) Biochemistry for the Medical Sciences, John Wiley, NY. and R.W. McGilvery (1979) Biochemistry: A Functional Approach. W. B. Saunders Company, Philadelphia)

Heavy exercise may also result in carbohydrate stress. There are two extreme situations:

First, if we look at athletes (human or animal) at these two extremes, there are significant differences in muscle types, thus for humans,

Let's look at the performance of world class runners as a function of distance (time). If we look at the figure below it appears that there are three processes (as shown by the three different best fit lines), indicating three different metabolic regimes corresponding to:

  1. The initial 20 seconds.
  2. The time from 20 to 200 seconds.
  3. Times exceeding 200 seconds.

Redrawn from R.W. McGilvery (1979) Biochemistry: A Functional Approach. W. B. Saunders Company, Philadelphia: p 704

Plot of rate of running vs. race length

Fuel Utilization in Prolonged Exercise

 

Fuel O2 utilization

 

Fuel Concentrations in Blood (mM)

  Blood-delivered Fuels
Exercise Time (min) Muscle Glycogen Glucose Fatty Acid Glucose Lactate Fatty Acid Glycerol
0       4.5 1.1 0.66 0.04
40 36% 27% 37% 4.6 1.3 0.78 0.19
90 22% 41% 37%        
180 14% 36% 50% 3.5 1.4 1.57 0.39
240 8% 30% 62% 3.1 1.8 1.83 0.48
Data from E. A. Newsholme & A. R. Leach (1983) Biochemistry for the Medical Sciences, John Wiley, NY. pp 370-372.

Plot of human fuel usage vs. exercise intensity as % maximum oxygen use

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© R. A. Paselk 2010;

Last modified 8 May 2013