Integration of Metabolism: Well-Fed and Fast State

Comprehensive vocabulary flashcards reviewing the integration of metabolism across the well-fed, fasting, and prolonged starvation states, covering organ-specific fuel utilization, hormonal control, and biochemical pathways.

Pancreatic β-cell insulin secretion

The multi-step process wherein glucose enters via GLUT2 and is phosphorylated by glucokinase; subsequent glycolysis, TCA cycle, and oxidative phosphorylation increase $[ATP]$, closing ATP-gated $K^+$ channels to cause membrane depolarization, opening voltage-gated $Ca^{2+}$ channels, and triggering $Ca^{2+}$-stimulated exocytosis of insulin granules.

Preproinsulin

The initial precursor of insulin synthesized by pancreatic β-cells that undergoes transport to the rough endoplasmic reticulum (rER), where cleavage of its signal peptide produces proinsulin.

C-peptide

A peptide cleaved from proinsulin along with the A- and B-chains that facilitates the proper folding of insulin and the formation of disulfide bonds before insulin packaging into secretory granules.

Insulinase

The primary enzyme responsible for the degradation of insulin, located mainly in the liver, which contributes to insulin's short plasma half-life of approximately $6\,\text{minutes}$.

Incretins

Gastrointestinal peptide hormones, including Cholecystokinin and Gastric Inhibitory Polypeptide (GIP), that stimulate pancreatic insulin secretion following food ingestion.

Glucokinase

An enzyme present in the liver and pancreatic β-cells characterized by a high $K_m$ and lower affinity for glucose than hexokinase, allowing these tissues to sense and respond directly to fluctuations in blood glucose concentration.

Post-absorptive state

The early phase of fasting occurring between $6$ and $12\,\text{hours}$ after the last meal, marked by a decreased insulin-to-glucagon ratio and the initiation of hepatic glycogenolysis to maintain blood glucose.

Fructose 2,6-bisphosphate

A hepatic regulatory intermediate synthesized by PFK-2 in response to insulin that allosterically activates PFK-1 to stimulate glycolysis and inhibits fructose 1,6-bisphosphatase to suppress gluconeogenesis.

Branched-chain amino acids (BCAAs)

Amino acids (leucine, isoleucine, and valine) that the liver has limited capacity to degrade; they pass through the liver essentially unchanged and are preferentially taken up and metabolized in skeletal muscle.

Counterregulatory hormones (Cortisol, Epinephrine, Glucagon)

Hormones that oppose the action of insulin: Cortisol provides for long-term changing requirements and stimulates gluconeogenesis; Epinephrine mobilizes fuels during acute stress via glycogen breakdown; and Glucagon mobilizes fuels and maintains blood glucose during fasting.

Glucagon

A 29-amino acid single polypeptide hormone secreted by pancreatic α-cells that acts via hepatocyte G protein-coupled receptors and cAMP-dependent protein kinase to activate glycogenolysis and gluconeogenesis.

Hormone-sensitive lipase (HSL)

An adipocyte enzyme activated by phosphorylation via glucagon, epinephrine, and sympathetic norepinephrine during fasting to hydrolyze stored triacylglycerols, and inhibited by insulin in the fed state.

Carnitine acyltransferase-1 (CAT-1)

The mitochondrial enzyme governing fatty acid uptake into the mitochondrial matrix for β-oxidation, whose inhibition by malonyl-CoA is relieved during fasting when hepatic fatty acid synthesis ceases.

Gluconeogenic precursors

Substrates converted into glucose by the liver during fasting, specifically lactate (from RBCs and exercising muscle), alanine (from skeletal muscle proteolysis), and glycerol (from adipose lipolysis via conversion to dihydroxyacetone phosphate).

N-acetylglutamate

An essential activator of carbamoyl phosphate synthetase I in the urea cycle whose synthesis is stimulated by glucagon in starvation to accelerate hepatic urea production from amino acid deamination.

Protein-sparing effect

The adaptation during prolonged starvation where the brain switches to deriving approximately two thirds ($\frac{2}{3}$) of its energy from ketone bodies, reducing the need for hepatic gluconeogenesis and sparing essential structural proteins.

Renal medullary cells and Red blood cells

Specific cell types containing few or no mitochondria that remain completely dependent upon anaerobic glycolysis of glucose for their energy needs across all metabolic states.

Pyruvate dehydrogenase (PDH) inhibition in starvation brain

The biochemical mechanism in cerebral tissue whereby the oxidation of ketone bodies to acetyl-CoA directly inhibits PDH, leading to reduced glycolysis and spared blood glucose during prolonged fasting.

Cardiac muscle fuel preference

A tissue-specific metabolic profile characterized by the utilization of fatty acids as the primary energy source in the well-fed state, and a combination of fatty acids and ketone bodies during fasting.