The Fed-Fast Cycle Flashcards
the absorptive/ well-fed state an anabolic period ?
due to the increased insulin-glucagon ration along with the readily available substrates circulating. available nutrients are captured as glycogen, TAG, and protein.
when do allosteric changes occur ?
allosteric changes usually involve rate-limiting rxns
how is glycolysis allosterically regulated in the liver following a meal ?
glycolysis is stimulated following a meal by an increase in fructose 2,6-bisphosphate, an allosteric activator of PFK-1. In contrast, GLUCONEOGENESIS is INHIBITED by fructose 2,6-bisphosphate, an allosteric inhibitor of fructose 1,6-biphosphatase
give examples of how insulin/glucagon can be responsible for induction and repression of enzyme synthesis.
insulin stimulates synthesis of enzymes like ACC and fatty acid synthase.
glucagon stimulates synthesis of PEPCK that converts oxaloacetate back to PEP (for gluconeogenesis)
liver is normally a glucose-producing rather than a glucose-using tissue. is that true after a carb-rich meal?
No. after a carb-rich meal, the liver becomes a net consumer, retaining roughly 60 of every 100 g of glucose presented by the portal system. this increased use reflects increased glucose uptake by the hepatocytes. their insulin-independent glucose transporter (GLUT-2) has alow affinity (high Km) for glucose, and therefore, takes up glucose only when blood glucose is high.
increased phosphorylation of glucose:
Liver in the absorptive state (well-fed):
indicate the mechanisms by which hepatic glucose metabolism is increased in each of the following:
high extracellular glucose–> high intracellular glucose –> glucokinase phosphorylates glucose –> G-6-P !
increased glycogenesis:
abundant G-6-P is an allosteric activator of glycogen synthase
increased activity of PPP
abundant G-6-P comibined with the use of NADPH stimulates PPP
increased glycolysis
once PDH is activated, it favors acetyl coA production; acetyl coA is then either involved in TCA cycle to harness energy for glycogen production or is involved in fatt yacid synthesis
fructose 1,6-bisphosphate is inhibited and other glycolysis enzymes.
increased fatty acid synthesis
Liver : well-fed state
abundance of acetyl coA (from fatt yacid and amino acid synthesis), NADPH (PPP), and activation of ACC via citrate: its allosteric activator. malonyl coA inhibits CPT-1 of fatty acid oxidation as well.
liver: fed state
Pyruvate cyt–PDH–> acetyl coA mit –> plus oxaloacetate –> citrate mit –> citrate cyt – ATP citrate lyase –> oxaloacetate plus acetyl coA. oxaloacetate –malate dehydrogenase –> malate – malic enzyme – > pyruvate.
Liver fed state
TAG synthesis is favored becasue fatty acyl coA’s are available both from de novo synthesis from acetyl coA and from gydrolysis of TAG component of chylomicron remnants removed from blood by hepatocytes. glycerol-3-phosphate, the backbone for TAG synthesis is provided by glycolysis. the liver packages TAG into VLDLs secreted into the blood for extrahepatic tissue use like muscle and adipose.
Liver Fed state
in absorptive state, more amino acids are pressent than the liver can use in synthesis of proteins and other nitrogem-containing compounds. surplus amino acids not stored but released into the blood for other tissues to use in protein synthesis or deaminated and resulting carbon skeletons being degraded by liver to pyrvate , acetyl coA, or TCA cycle intermediates –> can be metablized for energy or used in FA synthesis. leucine, valine, isoleucine (branched amin acids) pass through the liver unchanged.
liver well-fed state
adipose tissue ? (general)
adipose tissue is second only to liver in its ability to distribute fuel molecules. 70-Kg man, white adipose tissue WAT weighs about 14 Kg.
liver fed state
elevated insulin in absorptive state –> increased glucose influx into adipocytes via insulin-sensitive GLUT-4 recruited to cell surface from intracellular vesicles. glucose phosporylated by hexokinase.
liver fed state
abundant intracellular glucose –> enhanced glycolysis –> serves synthetic function of providing glycerol-3-phosphate for TAG synthesis
liver fed state
adipose tissue can metabolize glucose by means of PPP, producing NADPH for fatty acid synthesis. HOWEVER< in humans, de novo synthesis is not a major source of FA in adipose, except when re-feeding a previously fasted state. remeber that liver is the primary source of de novo synthesis of FA.
liver fed state
most fatty acids added to TAG stores of adipocytes after cinsumption of a lipid containing meal provided by degradation of dietary TAG in chylomicrons sent out by gut and endogenous TAG in VLDL sent out by liver. FAs released from lipoproteins via lipoprotein lipase LPL; extracellular enzyme attached to capillary walls in adipose and muscle tissue. LPL is upregulated by insulin
resting skeletal muscle fed state
fed state muscle takes up glucose via GLUT 4 for energy and glycogen synthesis and amino acids for protein synthesis. energy metabolsim of skeletal muscle is unique in being able to respond to body demands of STP that accompanies muscle contraction. skeletal muscle, despite its potantial for transient periods of anaerobic glycolysis, is an oxidative tissue.
primary source of energy in muscles fed state?
1# glucose
2# FA’s released from chylomicrons and VLDL via LPL
amino acid meabolism in the muscle fed state ?
the muscle is the principal site for degradation of BCAAs (leucine, isoleucine, and valine)because it contains the required transaminases. the BCAAs escape metabolism by the liver and are taken up by muscle, where they are used for protein synthesis.
FASTING state transition ?
fasting begins if no food is ingested after absorptive period. plasma levels of glucose, amino acids, and TAG fall –> insulin release –> decreased insulin-counteregualtory hormone ratio and decreased substrate availability –> CATABOLISM –> degradation of TAG, glycogen, and protein
two priorities:
1# the need to maintain adequate plasma levels of glucose to sustain energy metabolism in brain, RBCs , and other glucose-dependent yissues.
2# the need to mobilize fatty acids from adipose tissue and synthesis and release of ketone bodies from liver to supply energy to other tissues.
Liver fasting state CARBS
liver responses first by
1# glycogen breakdown –> glycogen phosphatase mobilized
2# gluconeogenesis –> carbon skeletons for gluconeogenesis derived primarily from glucogenic amino acids, lactate from muscle, and glycerol from adipose tissue. decreased availability of fructose 2,6-bisphosphate which actually inhibits fructose 1,6-bisphosphatase–> fructose 1,6 bisphosphatase actiavted along with PEPCK and Pyruvate carboxylase.
note that decreased fructose 2,6-bisphosphate inhibits glycolysis at PFK-1 step
liver FATSED state *fat metabolism*
oxidation of fatty acids (TAG hydrolysis) is the major source of energy in hepatic tissue in the postabsorptive state.
- NADH inhibits the TCA cycle
- acetyl coA is an allosteric activator of PC and allosteric inhibitor of PDH (favoring use of pyruvate in gluconeogenesis)
