8. the fed state Flashcards
when is the well fed state?
what state is the body in?
2-4 hours after a meal
anabolic state
what is oxidation or storage determined by
insulin/ glucagon ratio
what happens to proteins?
•cleaved by pepsin in the stomach and proteolytic enzymes in the pancreas
- absorbed into intestinal epithelial cells
- released into hepatic portal vein
•Free amino acids absorbed from blood used for protein synthesis & biosynthesis
- e.g. neurotransmitters & heme
- Carbon skeleton may be oxidised
amino acids are not stored
what happens to fats?
why can they be a problem?
they are not soluble for digestion can be a problem
•Triacylglycerols (TAGs)
- emulsified by bile sales
- pancreatic lipase converts TAGs to fatty acids & 2-monoacylglycerols
- form micelles contacting with bile salts
- Absorbed and then reformed into TAGs
- TAGs packaged with proteins, phospholipids, cholesterol into ‘chylomicrons’
how does the liver have a unique connection with digestive tract and circulatory system?
Venous drainage of gut & pancreas pass through the hepatic portal vein
- 1st organ bathed in nutrients & insulin
carbohydrate metabolism in the liver- what are the effects?
•Increased glucose uptake by hepatocytes
- Insulin dependent glucose transporters (GLUT-2) have high Km
•Increased Phosphorylation of glucose
- Glucokinase creates glucose-6-phosphate
•Excess glucose is converted to TAG
- Packaged into Very-Low Density Lipoproteins (VLDL)
•Increased Glucogenesis
- Glycogen Synthase is activated (by dephosphorylation) & by its allosteric effector, glucose-6-phosphate
- Converts glucose-6-phosphate to glycogen
•Increased activity of the Pentose Phosphate Pathway/Hexose monophosphate Shunt (10%)
-Again, due to glucose-6-phosphate and need for NADPH
Uses up to 10% of glucose metabolised
what causes an increase in glycolytic enzymes during carb metabolism in the liver? and which enzymes are these?
increased insulin:glucagon
increase in:
- glucokinase, PFK-1, & pyruvate kinase
- Pyruvate dehydrogenase (converting pyruvate to acetyl CoA) is dephosphorylated & active as pyruvate inhibits PDH kinase
how is there a decrease in the production of glucose during carbohydrate metabolism in the liver
- Gluconeogenesis & glycogenolysis are largely inactive
- Pyruvate carboxylase is largely inactive.
- Acetyl CoA being used for fatty acid synthesis
- Inactivation of fructose 1,6-bisphosphatase
- Dephosphorylation of glycogen- & phosphorylase-kinase
fat metabolism in the liver
primary site for fatty acid synth
- Increased during the absorptive state due to acetyl CoA & NADPH availability (from PPP pathway)
- Also, activation of Acetyl CoA Carboxylase catalyses acetyl CoA to malonyl
- Allosteric activator present, citrate
- Activated by dephosphorylation
•Increased Acetyl CoA:
- Pyruvate from glycolysis enters mitochondria
- Citrate leaves due to isocitrate dehydrogenase inhibition
- Cleaved by ATP-citrate lyase
•Increased Triacylglycerol synthesis:
- Increased acyl CoA presence & also due to hydrolysis of TAG component from chylomicrons
- Glycerol-3-phosphate is provided by glycolysis
what happens if amino acids are not used for protein synthesis in the liver?
exported to other tissues for use or degradation
degradation will involve deoeamination
- urea formed
- carbon skeleton (alpha keto acid) will be degraded to pyruvate, acetyl CoA, or TCA cycle intermediates
carbohydrate metabolism in adipose tissue
- Increased glucose transport
- GLUT-4 recruited by insulin
- Glucose phosphorylated (hexokinase)
- Glycolysis supplies glycerol 3-phosphate for TAG synthesis
- Pentose Phosphate Pathway ↑
- Produce NADPH (needed for fat synthesis)
- FA & glycerol released by lipoprotein lipase (LPL) in capillary walls
- Fat storage only limited by heart ?
carbohydrate metabolism in skeletal muscle
-Increased insulin-to-glucagon ratio & availability of glucose-6-phosphate favors glycogen synthesis
fat metabolism in skm
amino acid metabolism in skm
- FAs are of secondary importance compared to glucose
- Increased uptake of branched chain amino acids
- leucine,
- Isoleucine
- Valine
- Contains transaminase
brain tissue and BBB
•Substrates must be able to pass through blood brain barrier
- No significant glycogen stores
- No significant TAG stores
- Dependent on blood glucose
when can refeeding syndrome arise
what are the symptoms?
who can be at risk
after prolonged starvation, a meal can bring complications:
- Fluid & electrolyte disorders (hypophiosphatemia)
- Neurologic, pulmonary, cardiac complications
- Can lead to Death.
at risk if havent eaten for 7 days
- Consider after:
- chronic alcoholism- energy from alcohol
- anorexia nervosa
- Oncology patients
