Metabolic Homeostasis
carbohydrate, increases hepatic glycogenolysis, gluconeo-
genesis, and ketogenesis at the expense of fatty acid oxi-
dation and enhances adipocyte lipolysis. Epinephrine and
glucocorticoids are, respectively, acute and chronic indi-
cators of stress. They increase hepatic glucose output and
peripheral tissue fatty acid utilization. Growth hormone
regulates many processes associated with growth of the
organism. The energy for much of this growth derives
from fatty acid oxidation.
As fatty acids leave the adipocyte, they form complexes
with albumin. The availability of separate pathways for
fat deposition and release in these cells permits appropri-
ate regulation under anabolic or catabolic circumstances.
The absence of glycerol kinase in the adipocyte decreases
the potential for resynthesis of the triacylglycerol and
promotes hepatic gluconeogenesis. Triacylglycerols are
deposited in the adipocyte when glucose and insulin are
readily available.
F I G U R E 2 2 - 2 0
Regulation of fatty acid oxidation in cardiac muscle.
Tissue Utilization of Fatty Acids
The level of plasma albumin-bound fatty acids increases
when lipolysis rates are high. The tissue uptake of fatty
acids is proportional to their concentration in plasma and
is therefore largely dependent on blood flow. During in-
tense exercise, the flow of blood through the splanchnic
bed is reduced and more fatty acids are available to skele-
tal muscle. With the exception of nerve tissue and blood
cells, tissues can use fatty acids by /3-oxidation and by
the TCA cycle. Fatty acid uptake is not regulated by hor-
mones or intracellular effectors. Free fatty acids readily
diffuse across the plasma membrane of cells where they
are used strictly in response to supply and demand. This
is illustrated for cardiac muscle in Figure 22-20.
Fatty acid oxidation requires adequate amounts of NAD
and FAD. Oxidation of NADH and FADhF occurs in mi-
tochondria via electron transport and the use of molecular
oxygen. However, the electron transport chain can only
function if ADP is present, so that fatty acid breakdown
occurs at the rate necessary to maintain cellular levels of
ATP which decrease if metabolic or other work is per-
formed. Tight coupling of electron transport to oxidative
phosphorylation (Chapter 14) is of considerable impor-
tance in fuel economy. Without it, fatty acids would be
utilized in an unproductive manner. In the liver, fatty acids
in excess of requirements are converted to triacylglycerols
and secreted as VFDFs.
Many tissues preferentially utilize fatty acids as an
energy source. The sparing effect on glucose is il-
lustrated in Figure 22-21 and reflects the tight cou-
pling of oxidation of fatty acids to ATP production.
When sufficient fatty acids are available ATP concen-
trations will be high and ADP concentrations low. ADP
is required in two reactions in glycolysis; ATP is an
allosteric inhibitor, and AMP is an allosteric activator of
Ketone Body Production and Utilization
Fatty acids released from adipose tissue are the source
of ketone bodies (Figure 22-22). Fasting, high levels of
glucagon and catecholamine, and a low level of insulin re-
sult in rapid lipolysis and ready availability of fatty acids.
Fatty acids, after being converted to CoA thioesters, are
oxidized in the mitochondria. The rate-limiting step in
the oxidation process is the transport of fatty acyl-CoA
F I G U R E 2 2 -2 1
Glucose-sparing effect of fatty acid oxidation. Note the inhibition of
glucose utilization by high levels of ATP and citrate. OA, Oxaloacetate;
F-l, 6-bisP, fructose- 1,6-bisphosphate; 1,3-bisPG, 1,3-bisphosphoglyce-
rate; 3-PG, 3-phosphoglycerate; PEP. phosphoenolpyruvate; Pyr, pyruvate.
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