Humboldt State University ® Department of Chemistry

Richard A. Paselk

Chem 432

Biochemistry

Spring 2009

Lecture Notes: 11 February

© R. Paselk 2006
 
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Nitrogen Metabolism, cont.

UREA CYCLE COMPARTMENTATION

The enzymes involved in the conversion of amino acid nitrogen into urea occur in the cytosol and in the mitosol and involve three different catalytic systems: the Urea Cycle, The TCA cycle, and a transamination cycle, you might call them "Kreb's Tricycle." These interactions are shown in the figure in your packet ("Krebs' Tricycle"). Note the involvement of two antiports to move intermediates across the inner mitochondrial membrane: the malate: aspartate antiport, and the citrulline:ornithine antiport. Note also that nitrogen is incorporated in the mitosol (Transamination, Carbamoyl-P synthesis), whereas the final product, urea is released in the cytosol.

Tissue Distribution of Amino Acid Catabolism

Most amino acids are metabolized predominantly in the liver, but "alkyl" (branched chain) amino acids (val, leu, & ilu) are preferentially metabolized by skeletal muscle, whereas the "acyl" (asp, asn, glu, & gln) are metabolized in the intestinal mucosa. As an example let's look at the metabolism of protein after a one day fast (tissues need fuel and glucose). If we start with 1,000 mM of amino acids (equivalent to a "steak dinner" of 530 g of lean raw meat. (Data from McGilvery, Biochemistry: a Functional Approach, 1979, based on idealized calculations for amino acid distributions.):

flow diagram of the tissue specific utilization of  amino acids from steak

Note that most of the alanine coming to the liver is from the muscle and intestine, produced from amino acid nitrogen and pyruvate to keep serum ammonia concentrations down. One of the most striking aspects of this chart is the difference in tissue usage of ATP (note that all calculations are based on 3 ATP/NADH and 2 ATP/FADH2). Both muscle and intestine derive significant energy from the amino acids they breakdown. On the other hand, nearly all of the energy from the amino acids metabolized in the liver goes into glucose (very little ATP is made by the liver), which would go largely to the CNS (15,048 ATP @ 38 ATP's/Glucose, based on 3 ATP/NADH and 2 ATP/FADH2 used in the other calculations. If we use the values of 2.5 ATP/NADH and 1.5 ATP/FADH2, then we get 12,672 ATP @ 32 ATP/glucose)!

Alanine Cycle

Much of the nitrogen is carried between the tissues and the liver by the Alanine Cycle:

flow diagram of the Alanine Cycle

A similar, but more complex cycle involves glutamate/glutamine taking nitrogen from the muscle to the intestine where the glutamine is catabolized and the nitrogen goes to alanine which then goes to the liver. Glucose can then go to the muscle and be converted to glutamate via Glycolysis and the TCA cycle. We will not look at this more complex system.

Discussion of amino acid metabolism, lean meat, Lewis & Clark etc.

Catabolism of Amino Acid Carbon Skeletons

The catabolic breakdown of most of the amino acids is summarized in the Main Routes of Amino Acid Catabolism diagram in your packet. A couple of overview comments. Look at amino acids that are essential in mammals (cannot be synthesized in quantities necessary for good health: thr, phe{tyr}, his, lys, val, ilu, leu, arg). Amino acids can also be categorized as being glucogenic (can be used in Gluconeogenesis) or ketogenic (cannot be used in Gluconeogenesis). Most aa's can be at least partially used in glucose synthesis. For example ilu, tyr and phe are partially glucogenic and partially ketogenic (some carbons go to acetyl-CoA, while the rest go to TCA intermediates), while leu and lys are fully ketogenic.

 

We will begin by looking at the catabolism of amino acids by groups: 3-C (feed into pyruvate), 4-C (feed into oxalacetate), and 5-C (feed into glutamate).


Pathway Diagrams

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Last modified 11 February 2009