Ketogenesis: The production of ketone bodies by the liver in response to
increased P-oxidation with a decreased rate of the Krebs cycle as a result
of shuttling C4 acids from the mitochondrion for the synthesis of glucose
via gluconeogenesis.
Ketone bodies: Acetoacetate, P-hydroxybutyrate, and acetone. Acetoacetate
and P-hydroxybutyrate are formed by liver enzymes that condense
molecules of acetyl-CoA, thus regenerating CoA for continual use in
P-oxidation of fatty acids. Acetone is a spontaneous decomposition
product of acetoacetate. Ketone bodies are exported from the liver and
can be used by some extrahepatic tissues for energy generation.
Oxidative phosphorylation: The process by which adenosine triphosphate
(ATP) is synthesized from a hydrogen ion gradient across the mitochon-
drial inner membrane. The hydrogen ion gradient is formed by the action
of protein complexes in the mitochondrial membrane that sequentially
transfer electrons from the reduced cofactors nicotinamide adenine din-
ucleotide (NADH) and FADH2 to molecular oxygen. Movement of
hydrogen ions back into the mitochondrion via ATP synthase drives the
synthesis of ATP.
Protein phosphatase 1: An enzyme that will hydrolyze phosphate groups
from target proteins such as glycogen synthase, phosphorylase, phos-
phorylase kinase, and the phosphorylated form of inhibitor 1. The phos-
phorylated inhibitor 1 is a substrate that binds well but is hydrolyzed
slowly. While bound to protein phosphatase 1, the phosphorylated
inhibitor 1 serves as an inhibitor of the enzyme.
The liver is a highly specialized organ that plays a central role in whole body
glucose metabolism. During periods of increased glucose availability, the liver
increases uptake, storage, and utilization of glucose. In contrast, when exoge-
nous glucose availability declines (e.g., during an overnight fast), the liver
increases glucose production, thereby helping to maintain blood glucose levels.
The liver uses two mechanisms for endogenous glucose production, the mobi-
lization of intracellular glycogen (glycogenolysis) and the synthesis of glucose
from noncarbohydrate precursors (gluconeogenesis) (Figure 26-1). These
pathways converge at glucose 6-phosphate. The latter is hydrolyzed to free
glucose by glucose-6-phosphatase, the enzyme unique to gluconeogenic tis-
sues, such as the liver. Once generated, glucose passes down its concentration
gradient (e.g., from the cytosol of the liver cell to the blood during periods of
decreased blood glucose levels), via glucose transporter isoform 2 (GLUT 2).
During periods of increased glucose availability (e.g., postprandially), glu-
cose in excess of the energetic demands of the organism is stored as glycogen
(the storage form of glucose in mammals). Although found within the cytosol
of virtually every cell, glycogen is primarily concentrated in muscle (cardiac
and skeletal) and liver. The purpose of glycogen synthesis (glycogenesis) is to
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