21. Metabolic and physiological 'regulation' Flashcards
(34 cards)
Insulin: stimulates X. What happens?
Insulin stimulates lipoprotein lipase: if you had a high glucose meal, fatty acids are released from chylomicrons to make triglycerides in the adipocytes.
Metabolism changes with fasting. What happens with overnight fast?
Glycogen stores in liver used: gluconeogenesis important
Adipocytes do not take up glucose
Some muscle glucose uptake, much less.
Protein and fat breakdown in muscles more important
Fatty acids used for ATP (beta ox). Glycerol can be used for gluconeogenesis
Gut also produces glucose, and alanine
What happens upon starvation?
Muscle cells don’t take up glucose
More dependent on protein and fatty acid ox
Ketone bodies: Acetoacetate +beta hydroxybutyrate used by the brain
Kidney more important for gluconeogenesis. Produces glucose from aa’s.
What organs take up 60% of REE?
brain, liver, heart, kidneys
When fasting, brain still uses 4-5 g glucose/hr = 96-120 gr/day
Blood level: ~ 5 mM = 0.9 g/L
Hepatic glucose prod. = 180 g/day. Brain consumes what fraction of this?
About 2/3
Both glycogenolysis (glycogen-> glucose) and gluconeogenesis contribute both about 50% glucose production when fasting. These processes are induced by..? inhibited by ..? (hormones)
induced by glucagon
Inhibited by insulin
In post-absorptive state, most important organs in descending order for standard meal glucose production are.. (choose: kidney, intestine,liver)
And for fasting (24-48 hr)?
And in post-absorptive state of protein-rich diet?
- liver (70-75%)
- kidney (15-20%)
- intestine (5-7)
- kidney (50-55)
- Liver (20-25)
- Intestine (20)
- Kidney (40-45)
- Liver (40)
- Intestine (17-20)
What enzymes are very much regulated in glycolysis? What do they have in common?
- Hexokinase
- Phosphofructokinase
- Pyruvate kinase
They do not have a reverse pathway
Regulation of three glycolysis enzymes
Low conc of energy: ….. (same for pyruvate drhydr complex)
Hormonal regulation: by 1 and 2
enzyme flux will increase
insulin & glucagon
Insulin: expressed with..
Causes
1
2
Stimulates 3
high levels glucose in circ.
1 Glucose uptake
2. “” usage in cell
3. hexokinase, phosphofructokinase, pyruvate kinase
Glucagon: expressed when..
Inhibits 1, 2
fasting
> inhibits pyruvate kinase (to slow down the use of glucose)
> inhibits glycogen synthase
PFK1: Phosphofructokinase. Inhibited by? Stimulated by?
Inhibited by high levels of ATP, acetyl-CoA, citrate. (Citrate needs to be present in the cytosol. Is only present in the cytosol with high flux of TCA cycle)
Stimulation by AMP, low levels of O2
What reaction does pyruvate dehydrogenase complex start?
Pyruvate -> acetyl-CoA. Highly regulated.
High levels of 1 and 2 stimulate PDH (pyruvate dehydrogenase) kinases, which 3 the complex by phosphorylation
1 Acetyl-CoA
2. NADH
(its products)
3. inactivate
High levels of 1 or 2 or 3 inhibit PDH kinases: dephosphorylation results in 4 complex again.
1 pyruvate
2 CoA
3 NAD
4 active
What does insulin stimulate/block?
Stimulates glycolysis, blocks gluconeogenesis
What do glucagon & cortisol stimulate?
What hormones stimulate opposing enzymes?
stimulate gluconeogenesis, higher production of glucose.
Glucagon: makes sure there is enough glucose available
Insulin & glucagon stimulate opposing enzymes
What is the rate-limiting enzyme of TCA? By what is this enzyme regulated?
Citrate synthase
- energy (inhibited by high ratio’s of ATP over ADP, acetyl-CoA over CoA and NADH of NAD)
- product of the enzyme (citrate) or succinyl-CoA (another intermediate): also inhibiting
Fatty acids in cytoplasm: can be transported into mito’s, used through beta ox to produce CO2, oxygen, energy. Transporter enzyme = ?
CPT1 = CAT 1 = CARNITINE
CPT1 is a …. step for lipid metabolism
limiting
CPT1 is inhibited by..
Malonyl-CoA (intermediate in fatty acid synthesis)
When there is a lot of fatty acid synthesis happening in the cytosol, CPT1 = inhibited. “don’t start oxidizing we are synthesizing’
What happens with leptin (produced by adipose tissue) regulation? How does this cause an increased fatty acid oxidation?
- Signals to brain + muscle.
- In muscle: phosphorylates AMPK (low energy ATP), becomes active.
- Then, phosphorylates ACC, which becomes inactive.
- ACC regulates conversion of acetyl-CoA to malonyl-CoA.
- Less malonyl-CoA: ‘no fatty acid synthesis!’, no inhibition of CPT1: therefore leptin results in increase of fatty acid oxidation.
Mice that lack ACC , lack ..? They are ..?
(lack fatty acid synthesis), are very lean.
Problem with leptin: high levels of leptin -> you become …?
Problem with leptin: high levels of leptin -> you become a bit insensitive for it. Does not phosphorylate AMPK as much. AMPK stays inactive, ACC does not become inactivated. Still fatty acid synthesis.
