metabolic integration + organ specialization

liver

what organs carry out all the major metabolic pathways?

pyruvate and acetyl-CoA

what are the main 2 compounds at the crossroads of all the major metabolic pathways?

glycogen, glucose (ketone bodies during starvation), none

brain

• energy reservoir:

• preferred substrate:

• energy source exported:

glycogen, fatty acids, none

skeletal muscle (resting)

• energy reservoir:

• preferred substrate:

• energy source exported:

none, glucose (from glycogen), lactate

skeletal muscle (strenuous exertion)

• energy reservoir:

• preferred substrate:

• energy source exported:

glycogen, fatty acids, none

heart muscle

• energy reservoir:

• preferred substrate:

• energy source exported:

triacylglycerol, fatty acids, fatty acids + glycerol

adipose tissue

• energy reservoir:

• preferred substrate:

• energy source exported:

glycogen + triacylglycerol, amino acids + glucose + FA, FA + glucose + ketone bodies

liver

• energy reservoir:

• preferred substrate:

• energy source exported:

brain, Na/K, independent, ketone bodies

• _____ makes up 2% of body mass but 20% of resting oxygen consumption

• mainly, ____ pumps (ATPase)

• oxygen consumption _____ of mental activity

• during prolonged glucose starvation, gradually develops ability to use _____

neurons (metabolic trafficking in brain cells)

lactate produced anaerobically in support cells (astrocytes/oligodendrocytes) is used for further oxidation in _____

AMP

• glycogen in neurons/astrocytes critical for brain function during hypoglycemia, hypoxia, ischemia

• low glucose or low oxygen → high ___ → rapid glycogen mobilization

skeletal muscle, 90%, Ca2+

• ____ makes up 30% of resting oxygen consumption and ____ of oxygen consumption during max exertion

• burns fatty acids, sugars, ketone bodies

• nerve impulse → ___ release → contraction

• increases glycolysis rate 200x and respiration rate 25x

free ATP

ATP source for short activities (5 seconds)

phosphocreatine

ATP source for sprints (10 seconds)

glycolysis

ATP source for races (1.5 mins)

oxidative phosphorylation (aerobic - requires oxygen)

ATP source for long races (3+ mins)

phosphocreatine

• stores high energy phosphate for quick ATP formation

• creatine kinase transfer phosphate from ____ to ADP → ATP + creatine

pH, PFK

• when muscles fatigue, they produce lactate which lowers ___

• → lower ____ (uses ATP to convert F6P → FbisP) activity preventing complete ATP depletion

anaerobically

muscles store glycogen rather than fat because it is mobilized more quickly and the glucose can be used ____ whereas fatty acids cannot

glycogen stores, fat

runner “hit a wall” after 60-120 mins because their _____ are depleted and burning ___ for fuel is less efficient (slower and requires more oxygen)

heart, aerobic, fatty acids

• ____ has continuous rhythmic contraction

• completely ____

• normally burns ____

• minimal energy reserves (small amount of phosphocreatine, glycogen)

adipose tissue, lipoproteins, TAGs (triacylglycerols)

• primary role of ____ is to store and release FA

• FA for storage comes from ____

• ____ are hydrolyzed by hormone-sensitive lipase

liver, glucose

• ____ maintains proper levels of circulating fuels for use by other tissues

• all nutrients absorbed by small intestines pass through the portal vein to the liver (except FA)

• acts as blood ____ buffer

glucose, glycogen, ribose-5-P, acetyl-CoA

in the liver, glucose-6-P can be converted to ___, ___, ___, or ___

ketone bodies

liver produces ___ that are only utilized by other organs because liver doesn’t have 3-ketoacylCoA-transferase)

fatty acids, triacylglycerols

during fed state, liver exports ___ by incorporating them into _____ and secreting them into the bloodstream as VLDL

amino acids, glucose

liver uses dietary ____ for energy after a meal but during fasting ___ is produced from amino acids that were produced from protein degradation

adipose tissue (burning fat)

liver gets ATP and NADH for gluconeogenesis from ____

TAG, ketone bodies, proteins

• liver provides fuel for brain during prolonged exercise/starvation

• ____ from adipose tissue (glycerol → liver → DHAP → glucose)

• ____ from liver (brain gradually shifts to using this)

• degradation/export of muscle ____ (glucose/alanine cycle → glucose in liver)

pyruvate

• muscle aminotransferases convert ____ to alanine (glucose-alanine cycle)

• mechanism for transporting nitrogen from muscle to liver

Cori cycle

liver recycles lactic acid from muscle to glucose via ____

kidney, pH, glutamate, glutamine

• ____ removes wastes while recovering metabolites

• maintains buffer blood ____ by regenerating bicarbonate lost by exhalation of CO2

• removes amine from ___ and ___ to excrete as ammonium

• performs gluconeogenesis (only organ besides liver)

beta, insulin

as blood glucose increases, ___ cells produce ____ in pancreas islet cells

alpha, glucagon

as blood glucose decreases, ___ cells produce ____ in pancreas islet cells

GLUT2 (glucose transporter in liver), glucokinase

beta cells of pancreas use ___ and ____ to sense blood glucose concentration in order to regulate hormone secretion

GLUT4

transports glucose across cell membrane in muscle and adipose tissue (regulated by insulin)

fed (glucose present, insulin binds to receptors)

in a ___ state, hormonal control leads → lipogenesis in adipose tissue and liver, glycogen synthesis in muscle and liver

fasted (glucose not present, glucagon and epinephrine binds to receptors)

in a ____ state, hormonal control leads → glycogenolysis in muscle, lipolysis in adipose tissue, gluconeogenesis in liver

type I

• diabetes mellitus that is insulin dependent

• lack of/defective beta cells

• treat with diet + insulin injections

type II

• diabetes mellitus that is not insulin dependent

• doesn’t respond properly to insulin

• more prevalent in obese individuals

cataracts

• TAG → ketone bodies → excess = ketosis

• blood pH goes down

• uncontrolled diabetes

AMPK (AMP dependent protein kinase)

many diabetes treatment focus on ____ because it increases pathways that make ATP and decrease biosynthetic paths that use ATP

metformin

• _____ increases AMP → activates AMPK → increases beta oxidation → decreases gluconeogenesis

• reduces glucose release from liver

metformin, adipose tissue

• increased FA in blood interferes with insulin induced glucose uptake by muscle so lowering blood FA → increased insulin response

• can lower FA in blood by increasing FA uptake by muscle with ____

• can lower FA release by _____