Six Flashcards
(16 cards)
What is the timeline for anabolism? What are the hormones that are increased? Decreased? What is the fuel source? What cellular processes are taking place? Same questions for catabolism.
- Anabolism begins with food ingestion, lasts 2-3 hrs, characterized by energy storage because caloric intake exceeds caloric demand
Hormones: Insulin, Leptin, GI peptides, decr. glucagon
Fuel Source: Diet
Cell Process: Glycogen, protein, lipid synth.
- Catabolism begins 4-6 hrs after eating and is characterized by a shift to endogenous fuels (mobilization of substrate from liver, muscle, adipose tissues)
Hormones: Decr. Insulin, incr. catecholamines, incr. glucagon
Fuel Source: Glycogen, fat depots, muscle protein
Cell Process: Gluconeogenesis, glycogenolysis, lipolysis, ketogenesis, proteolysis
In the anabolic phase, where does glycogen synth occur? FA synth and TG formation? Protein synth? What substances are increased postprandially? Decreased?
Anabolic phase (Fuel storage):
- glycogen synthesis in liver
- FA synthesis and TG formation in hepatocytes and adipocytes
- protein synthesis in hepatocytes, muscle and other tissues
- Postprandial increases: Plasma glucose, TGs, AAs
- Postprandial decreases
a. Plasma FFAs
b. Plasma ketones (acetoacetic acid, beta-hydroxy butyric acid)
c. Plasma glycerol
In the catabolic phase, which cellular processes/substances will be increased? Decreased?
Catabolic phase (Fuel flux):
- Increased
a. Glycogenolysis
b. Gluconeogenesis
c. Lipolysis, FFA oxidation, ketone formation
d. Proteolysis
e. Plasma levels of AAs, long chain FAs - Decreased:
a. Glycolysis
b. Lipogenesis and TG formation
c. Plasma glucose and TGs
What two things occur in the abscence of food to prevent hypoglycemia?
Two changes are required to maintain plasma glucose
within normal range in the absence of food:
- Liver converted to an organ of glucose
production
- Non-CNS tissues converted to lipid utilization
(FFAs or ketones), **CNS gets what glucose there is
and then can shift to ketone utilization
List the hormones involved in regulating fuel metabolism and their primary role.
Hormones regulating fuel metabolism:
Insulin – primary mediator of anabolism
Glucagon – preeminent inducer of catabolism
Counter regulatory hormones: glucagon, Epi,
Norepi, GH, cortisol
At what levels of plasma glucose do insulin levels fall? Rise? When do glucagon levels fall? Rise? What stimulates postprandial insulin secretion? What inhibits postprandial glucagon secretion? What stimulates postprandial glucagon secretion? Why?
Insulin and Glucagon vary reciprocally (with one exception).
- When plasma glucose
During stress, what hormones have an effect on glucagon and insulin? What is their effect? What is their mechanism? What are 3 results of this?
In Stress:
- Epi and Norepi cause
a. Increased glucagon secretion (beta adrenergic mechanism, via an increase in cAMP)
b. Decreased insulin secretion (alpha2 adrenergic mechanism, via decreased cAMP) - Results in:
a. Increased glucagon : insulin ratio
b. Increase hepatic glucose output
c. Protection against hypoglycemia
What occurs in both beta cells and alpha cells in both low glucose and high glucose states (cellular pathways)? What function do paracrine factors have?
Low glucose:
Beta cells –open KATP channels, hyperpolarized, electrically inactive
Alpha cells – electrically active, increased ATP/ADP ratio, closed KATP channels (most), depolarization opens Na+, Ca++ (VDCC), K+ channels leading to exocytosis
High glucose:
Beta cells – glucose enters, glycolysis, increased mitochondrial oxidative metabolism, increased
ATP/ADP ratio, closes KATP channels, depolarization, exocytosis
Alpha cells – further increased ATP/ADP ratio closes KATP channels, further depolarizing the cell resulting in closure of Na+ and VDCC channels, decreasing glucagon release
Paracrine factors: insulin, GABA, Zn++ from Beta cells; Somatostatin from Delta Cells
Describe the pathways that occur in the anabolism of glucose in both muscle cells and liver cells.
Muscle: glucose glucose-6-phosphate glucose-1-phosphate UDPglucose glycogen
Liver: glucose or lactate substrate glycogen
glucose lactate/pyruvate citrate acetyl CoA malonyl-CoA palmitate other fatty
acids
Describe the exogenous pathway of fat metabolism.
Exogenous pathway: dietary triglycerides (Pancreatic lipase & colipase) long chain FAs
and 2-monoglycerides (Bile salts) micelle (diffusion)
Apoprotein CII and heparin activate Lipoprotein Lipase (luminal surface of endothelial cells).
Lipoprotein lipase removes long chain FA’s from position 1 and 3 leaving 2-monoglycerides
(hydrolyzed intracellularly). Released FA’s carried bound to albumin to adipocyte for re-
esterification and muscle for energy production (oxidation).
Chylomicron remnants contain some TGs, but most cholesterol and cholesterol esters. Apo E on
remnant interacts with receptor (LDL-related receptor protein, LRP) and contents cleared.
- Short and medium chain FAs portal vein as FFAs
- Reformed TGs (packaged as chylomicrons) lymph
Describe the endogenous pathway for fat metabolism.
Endogenous pathway: TGs
of hepatic origin VLDL
(lipoprotein lipase,
activated by Apo CII
removing most of TGs)
ILD/HDL/LDL.
Both IDL and LDL cleared
by interaction with LDL
receptor (liver and many
other tissues, providing
cholesterol for steroid
synthesis and membrane
formation).
Partial or complete lack of
LDL receptor results in
hypercholesterolemia and premature atherosclerosis.
Describe protein anabolism.
Pepsin and acid pancreatic proteases (endo- and carboxypeptidases) portal vein
liver (except branched chain amino acids: valine and isoleucine which go directly to muscle)
protein synthesis (stimulated by insulin)
Describe the role of 6-phosphofructo-2-kinase/fructose-2,6-bisphophatase in both anabolism and catabolism. Summarize this pathway. What are some substrates for gluconeogenesis?
During Anabolism:
Insulin levels high, glucagon low
Bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase
(PFK2/FBPase2) is dephosphorylated and functions as a kinase
Fructose-2,6-bisphosphate is formed favoring glycolysis by stimulating phosphofructokinase (#1)
During Catabolism:
Insulin levels fall and glucagon levels increase
PFK2/FBPase2 is phosphorylated and functions as a phosphatase (kinase activity lost)
Fructose-2,6-bisphosphate levels fall releasing inhibition of fructose bisphosphatase (#2)
Insulin > Glucagon: Fructose –1,6 – bisphosphate > Fructose – 6 – phosphate (Glycolysis)
Glucagon > Insulin: Fructose – 6 – phosphate > Fructose –1,6 – bisphosphate (Gluconeogenesis)
Summary: Hypoglycemia –>incr. glucagon and catecholamines —> incr. cAMP —> incr. phosphorylation
of PFK2/FBPase2 —> decr. F-2,6-bisphosphate—>decr. inhibition of biphosphatase—-> more F-6-Phosphate—> decr. glycolysis and incr. gluconeogenesis
Substrates for gluconeogenesis: Lactate (incomplete oxidation in peripheral tissues), glycerol
(triglyceride utilization in adipocytes), amino acids
What are some signals for proteolysis? What are some bad results? What prevents these results? How are the free amino acids used? Which AAs can leave muscle tissue?
Signals for proteolysis:
- decreased insulin
- increased cortisol
- increased catecholamines
- ? increased glucagon
Resulting in: cell breakdown, protein wastage, arrhythmias
“Release”: In starvation, switch to lipid economy reducing need for gluconeogenic substrate
In muscle, proteins are broken down leading to AAs. Most AAs are used as an energy source in muscle. Glutamine and Alanine leave the tissue and enter the blood stream. Glutamine enters the bloodstream and undergoes gluconeogenesis. Alanine does the same thing in the liver.
What happens in the switch to a lipid economy? What are some stimulators for hormone sensitive lipase? Some inhibitors?
Switch to lipid economy requires changes in liver and fat
(hydrolysis delivering long chain FFAs and glycerol to
the circulation). 66% of FAs used directly as energy
source, rest taken up by liver for ketogenesis.
Stimulators of hormone sensitive lipase: catecholamines,
glucagon, GH, cortisol
Inhibitors of hormone sensitive lipase: insulin, adenosine
Describe how glucagon stimulates ketogenesis.
Glucagon:
- blocks glycolysis so levels of pyruvate, citrate and malonyl-CoA fall (normally, pyruvate is converted to acetyl coA which is converted to citrate which is converted to malonyl CoA which is converted to a FA which is converted to a fatty acyl CoA which is used to form TGs)
- directly blocks Malonyl CoA formation
- by lowering Malonyl CoA levels, CPT-1 is disinhibited (normally, Malonyl CoA inhibits CPT-1)
- CPT-1 transesterifies carnitine (exchanges for CoA of the fatty acyl CoA) and fatty acylcarnitine transported to mitochondria
- fatty acylcarnitine retransesterified to fatty acycl
CoA and then beta oxized to ketones
