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chapter
22
Metabolic Homeostasis
needing less glucose from the liver. Two ketone bodies are
acids and give rise to acidosis which is decreased by their
elimination in urine. In a 24-hour fast, a 70-kg person
hydrolyzes approximately 160 g of triacylglycerol, with
release of 160 g of fatty acid and 16 g of glycerol. The
glycerol is used for gluconeogenesis. Of the fatty acids,
approximately 40 g is metabolized to ketone bodies in
liver; the remainder and these ketone bodies provide for
the energy needs of all other tissues.
22.7
Protein Synthesis and Nitrogen Homeostasis
Protein Synthesis and Proteins as Energy Source
While carbohydrates and lipids are essential for structural
and functional needs of cells and organs, the principal
changes in their fluxes reflect fuel homeostasis and en-
ergy requirements. Protein homeostasis is different be-
cause no protein serves purely as an energy storage form.
All proteins—in addition to being potential sources of car-
bon for energy—serve some structural, catalytic, trans-
port, or regulatory function. Many fluctuations observed
in protein metabolism reflect changes in the need for the
function of that protein. Thus, in starvation the total rate
of skeletal muscle protein synthesis decreases but that of
protein degradation increases because the amounts of pro-
teases and enzymes involved in the catabolic routes for
amino acids increase. Thus, starvation stimulates the spe-
cific synthesis of some proteins.
Protein anabolism and catabolism are governed by
many forces. Some rules apply:
1. Which specific proteins are synthesized in a cell is
governed entirely by the needs or functions of the cell
at that time.
2. Synthesis of specific proteins is triggered by a specific
signal.
3. Synthesis of a specific protein may not occur if the
general “anabolic state” of the cell is low.
4. The anabolic state is reflected by metabolite
availability and the presence of anabolic or catabolic
hormones.
5. Synthesis occurs if the strength of the specific trigger
overrides that of catabolic messages or other
hormones or metabolites.
6
. Degradation of a protein may occur if
a) the protein has no function in the cell,
b) a specific trigger to initiate degradation is present,
or
c) the state of the cell is sufficiently catabolic as a
result of the presence or absence of specific
metabolites or hormones.
Many hormones modulate the amounts and types of pro-
teins synthesized and their rates of degradation. One group
functions on very few target cells, e.g., TSH (thyroid-
stimulating hormone) on the thyroid gland, FSH (follicle-
stimulating hormone) and LH (luteinizing hormone) on
the gonads, or ACTH (adrenocorticotropic hormone) on
the adrenals. Another group has widespread action on pro-
tein metabolism, e.g., insulin, glucocorticoids, growth hor-
mone, and thyroid hormone. Many sites of action of insulin
and glucocorticoids remain to be elucidated. Glucocorti-
coids act at the gene level and promote peripheral tissue
protein degradation, delivery of amino acids for gluconeo-
genesis, and adipocyte lipolysis.
Insulin stimulates peripheral tissue protein synthesis by
stimulating amino acid uptake and protein synthesis at the
level of translation and by inhibiting protein degradation.
At low insulin levels, muscle proteolysis occurs. As the
levels increase, proteolysis decreases and protein synthe-
sis is favored. Exercise decreases proteolysis and increases
protein synthesis, whereas disuse results in muscle wasting
and depressed protein synthesis. Exercise increases sensi-
tivity to insulin, whereas disuse makes the tissue insulin-
resistant. Obesity, pregnancy, and glucocorticoids also
increase insulin resistance.
Nitrogen Balance
Unlike most carbohydrate and lipid, protein contains nitro-
gen required for incorporation into a wide range of com-
pounds (Table 22-4). Although the synthesis of proteins
fixes nitrogen into those proteins, they are synthesized in
direct response to specific needs. Dietary protein nitro-
gen is used for the synthesis of nitrogen-containing com-
pounds in response to specific hormones suchas insulin.
T A B L E 2 2 -4
Compounds for Which Amino Acids Serve as Precursors
Amino Acid Precursor
Product
Glycine, aspartate,
Purines
glutamine
Aspartate, glutamine
Pyrimidines
Glycine
Porphyrins
Arginine, methionine
Polyamines
Arginine, glycine
Creatine
Tryptophan
Serotonin, melatonin
Tyrosine
Catecholamines,
dopamine, melanin
Histidine
Histamine
Arginine
Nitric oxide
