glycolysis and gluconeogenesis Flashcards
what process is occuring when pyruvate is converted to OOA?
carboxylation
what does PEP carboxylase do?
carboxylates (adds carbon dioxide ) to form OOA and and inorganic phosphate
what is the fate of pyruvate when using pyruvate carboxylase?
adds a carbon to pyruvate forming OOA
what is the fate of OOA when using PEP carboxykinase?
PEP- helps reverse pyruvate kinases effect and decarboxylates and phosphorylates PEP when GTP is present
Is pyruvate kinase a reversible or irreversible reaction?
irreversible
does pyruvate kinase phosphorylate pyruvate?
no it is a substrate level phosphorylation enzyme that produces ATP/ makes ATP. so it takes the phosphate from PEP and gives it to ADP and cannot be reversed
why is pyruvate kinase a irreversible reaction?
because it has a large negative free energy charge
when pyruvate kinase is phosphorylated what happens to pyruvate?
pyruvate kinase is inhibited when it is phosphorylated to allow gluconeogenisis to occur and pyruvate will not be formed
what enzyme cleave fructose 1,6 bisphosphate, which is the second/ regulating step in gluconeogenesis?
fructose 1,6 bisphosphatASE, which inhibits glycolysis by inhibiting PFK-1 from making fructose 1,6 bisphosphotase
what is the enzyme used in the main regulated step in glycolysis?
phosphofructokinase 1- phosphorylates fructose 1,6 bisphosphosphate
where is the phosphate group added when using phosphofructokinase 1?
position 1 on the fructose (fructose 1,6 bisphosphate)
in gluconeogenes, since pyruvate is an irreversible reaction, what are the 2 enzymes that allow an alternate pathway to reverse the effect of pyruvate kinase/ irreversible step?
pyruvate carboxylase and pep carboxykinase
what molecule do we need alot of in the first step of gluconeogenesis for gluconeogenesis which is an unfavorable reaction to become favorable?
alot of OOA from the kreb cycle needs to be produced so PEP carboxylase/ pyruvate carboxylase is used to add a carbon to pyruvate to make OOA, after we have OOA, the second enzyme PEP carbokinase convertes OOA to PEP known as the alternate step in gluconeogenesis
what is the difference between bisphosphate and diphosphate?
For a diphosphate, the 2 phosphate groups in the compound are directly attached to one another.
For a bisphosphate, the 2 phosphate groups in the compound are attached to different atoms on the compound, meaning that they are not attached to one another.
why does phosphoaditylinistol bispohospahate have three phosphates?
because it needs to form IP3
what is the fourth enzyme used in gluconeogensis to make glucose 6 phosphate to glucose?
glucose 6 phosphotASE
what are the 4 regulated steps gluconeogenesis?
pyruvate carboxylASE, PEP carboxykinase, Fructose 6 bisphosphotASE, glucose 6 phosphotASE
what is the purpose of gluconeogensis?
because we have cells that do produce there own energy/fuel such as the renal medulla, the brain, and the RBC gluconeogensis helps keep and maintain there energy when the energy level is low(fasting when gylcogen stores are done)
when does gluconeogensis/ glucagon happen?
when the glycogen store( are limited) are low/depleted, fasting, or fight or flight
what does the urea cycle do?
gets rid of nitrogen
does glycogen degradation and gluconeogenesis occur at the same time?
yes but glycogen degradation is the main source out of the two until all of the stored glycogen is depleted
what 2 organs allow gluconeogenesis to occur?
liver and the kidney
if have ethanol abuse to the liver, (being mean to the liver), then it will not be able to do what?
gluconeogenesis or glycolysis
does the kidney/renal medulla form or use glucose?
uses glucose
does the renal cortex form or use glucose?
forms glucose
if have a overnight fasting where will gluconeogenesis occur?
90% in the liver and 10% in the renal cortex(kidney)
if have a prolonged fasting 10-40 days, where will gluconeogenesis occur?
60: in the liver and 40% in the renal cortex(kidney), so there is an increase of gluconeogenesis in the kidney and and less of gluconeogenesis in the liver
At the cellular level, is gluconeogenesis found only in the cytoplasm?
no it is needed in the liver and the mitochondria (puruvate carboxylase-kreb cycle)
what substrates does the mitochondria need when in the fasting state?
lactate, pyruvate and glycogenic amino acids
where is PEP carboxykinase found at the cellular level?
in the mitochondria and cytosol
why would lactate be needed in gluconeogenesis?
to make pyruvate so that pyruvate can be carboxylated by pyruvate carboxylase to be converted into OOA so that OOA can be converted into PEP by using PEP carboxykinase
so is having a high level of lactate in the cell during the fasting state bad?
no because we use and convert lactate so that it can form glucose to produce energy
where is pyruvate carboxylase located at the cellular level?
mitochondria
what are the two main amino acids that the liver pick up from the blood?
alanine and glutamate( this is used for the urea cycle and this is how nitrogen is trasported to the urea cycle)
what does glucogenic amino acid mean?
amino acids can be used for gluconeogenesis (alanine and glutamate)
can the carbon skeleton be used for gluconeogenesis?
yes when the liver wants to do it
when the liver chooses to do glycolysis and it is in affect, what happens to alanine and glutamate?
they are degraded
when the liver chooses to do gluconeogenesis and it is in affect, what happens to alanine and glutamate?
they are used, and the urea cycle gets its nitrogen this way to make ammonia and the carbon skeleton is used as well
is gluconeogenesis a reversal of glycolysis?
no, it just uses the same enzymes
why cant glycolysis and gluconeogenesis happen at the same time?
tight hormonal regulation ensures that they do not happen simultaneously
what hormones favors gluconeogenesis?
Glucagon and cortisol
what hormones inhibit gluconeogenesis?
Insulin
what hormones favor glycolysis?
insulin
what enzyme enzyme allow PFK-1 to be activated and at the same time inhibits fructose 6 bisphosphotase?
fructose 2, 6 bisphosphate
what inhibits fructose 1,6 bisphophotASE?
fructose 2, 6 bisphosphate
where is fructose 6 phosphatASE bound?
the ER toward the ER lumen
what is T1?
glucose 6-P translocase
what is T2?
transports Pi
what is T3?
GLUT-7 transports glucose from ER lumen into cytosol
what is SP?
stabilizing protein
where is the generated glucose released into the blood?
GLUT-2 in the plasma membrane
where is glucose 6 phosphotase found?
in the kidney and liver
why is glucose 6 phosphotase needed?
to allow for free glucose molecules to leave the liver to go to the blood stream
when does TAG degradation take place?
TAG degradation takes place in fat cells only during fight or flight situation—releases free fatty acids and free glycerol to the liver
what is hormone sensitive lipase?
it is the enzyme that helps with degradation of TAGs
what describes the interactions between muscle and the hepatocytes during fasting?
the cori cycle and the alanine glucose cycle
when the TAGs are released from the adiopose tissue what are they then cleaved into ?
free glycerol backbone and fatty acids
in gluconeogenesis , where is lactate given off of in the body ?
in the muscles ( RBC) to the liver for conversion into glucose
in gluconeogenesis, where is alanine and glutamine given off of in the body?
in the muscles (and other cells) to the liver
there is a high abundance of alanine and glutamine in the body, what has the patient not done in a day or so?
eaten a meal, so his body is in the fasting state and gluconeogenesis is occuring and glycogen degradation occurs simutaneously until it runs out then gluconeogenesis takes over
what metabolism is used when lactate is produced?
anaerobic metabolism in the muscles
what does the formation of lactate from pyruvate need?
needs lactate dehydrogenase and NAD+ as a coenzyme
when lactate is produced what is it taken up by?
the blood
are red blood cells independent of a nutritional state?
yes, meaning if your in your fast or fed state then you are still going to get energy to the RBC regaurdless
when alanine makes pyruvate, what is the name of this process?
transamination
when alanine is elevated what state are we in?
fasting
when alanine is in the blood what cells take them up, so that they can create pyruvate?
hepatocytes- liver cells
in order for alanine to make pyruvate what is needed ?
alpha keto glutarate and alanine aminotransferase
what is the coenzyme needed when making pyruvate out of alanine?
PLP (pyridoxal phosphate)
what cycle are alanine and glutamine transported to in the liver?
the urea cycle
where is alanine and gluatmine released from?
the muscles
when there is an increase of alanine and glutamine, what hormone is low?
insulin
during muscle protein degradation are alanine and glutamine high or low levels?
high, proteins are being degraded
what is the cori cycle?
the metabolic pathway in which lactate produced by anaerobic glycolysis in the muscles moves to the liver and is converted to glucose, which then returns to the muscles and is metabolized back to lactate.
at the cellular level, where is alanine converted to pyruvate?
cytosol
why is alanine aminotransferase special?
it is a injury marker for the liver
what is used for pyruvate carboxylase to fucntion?
carbon dioxide and botin(prosthetic group)
is ATP cleaved or produced in the process of pyruvate carboxylase making OOA?
it is cleaved and the phosphate is absorbed and used
in the mitochondria, pyruvate carboxylase needs this as a allosteric activator?
it needs acetyl CoA
when carbon dioxide is activated, pyruvate carboxylase carries it to what?
biotin its prosthetic group
after pyruvate carboxylase transfers carbon dioxide to biotin, what does it generate?
OOA
when OOA is formed, and cannot cross the membrane, what has to happen?
it has to change into malate to cross the mitochondrial membrane and then it is converted back to OOA in the cytosol
do we need biotin (a vitamin), for all carboxylases?
yes except vitamin K( gamma carboxylation)
how is malate converted back to OOA in the cytosol?
it is reoxidized to OOA , which is oxidatively decarboxylated to PEP by PEP carboxykinase
What does PEP carboxykinase need as substrates to form PEP ?
it needs OOA and GTP—->PEP, GDP, CO2
what is used to form OOA?
NAD+( so that it can be oxidized) and malate to form OOA which is the substrate for the cystolic form of PEP carboxykinase
what does PEP carboxykinase uses as its energy?
GTP, does not care about ATP
is PEP carboxykinase a G protein?
yes, it uses GTP
what does UTP activate? (ATP CAN MAKE-USED UP and then make another fuel currency GTP)
sugar
what does CTP activate?
lipids
what does GTP activate?
liver,translation, g protein(PEP carboxykinase)
when does the liver switch glycolysis to gluconeogenesis?
when glucagon is abundant
what is special about the isozyme of pyruvate kinase?
protein kinase A can phosphorylate and inactivate it,
what is the puropse of the isozyme (aka as the short form dependent cyclic AMP(cAMP) protein kinase) of pyruvate kinase to be phosphorylated and inactivated?
it assures that PEP is saved for gluconeogenesis
can gluconeogenesis happen when there is no fatty acid degradation going on at the same time in the mitochondria?
no, gluconeogenesis can only perform gluconeogenesis when it degrades at the SAME time fatty acids in the mitochondria degrade
What leads to degradation of TAGS in fat cells?
when gluconeogenesis takes place during fasting and low insulin/glucagon ratio in the blood
after TAGS in fat cell are degraded what happens?
free fatty acids are then released from adipocytes into the blood, bound to albumin and taken up into hepatocytes and other tissue
when does TAG degradation take place?
TAG degradation takes place in fat cells only during fight or flight situation—releases free fatty acids and free glyserol to the liver
what is hormone sensitive lipase?
it is the enzyme that helps with degradation of lipids
what do low insulin levels activate to be released from the muscles in the adipose tissue?
TAGs- glycerol storage
when the TAGs are released from the adiopose tissue what are they then cleaved into from the hormone sensitive lipase ?
free glycerol bacbone and fatty acids
is citrate synthase regualated in humans or bacteria by NADH?
in bacteria.
In humans, citrate synthase is inhibited by the product citrate
in the citric acid cycle, in humans, what is the first enyzme that is inhibited by NADH?
isocitrate dehydrogenase
what is the second enzyme inhibited by NADH in the kreb cycle?
alpha keto glutarate dehydrgenase
Does gluconeogenesis and mitochondrial beta oxidation of fatty acids take place at the same time during fasting in the hepatocytes?
yes
when the liver degrades the fatty acids in the mitochondria using beta oxidation what is generated?
NADH and acetyl CoA
what is NADH and acetyl CoA used to regulate?
PDH complex, TCA cycle and gluconeogenesis
what happens when the acetyl CoA and NADH are newly generated?
they inhibit the pyruvate dehydrogenase complex(PDH)directly by product inhibition and also indirectly by activation of PDH kinase
what does acetyl CoA allostrically activate?
pyruvate carboxylase
what is used during fasting for hepatic ketone body formation?
acetyl CoA
What does NADH inhibit in the TCA cycle?
isocitrate dehydrogenase, alpha keto glutarate dehydrogenase complex and the formation of malate from OOA is favored(gluconeogenesis)
what is the ultimately regulated enzyme in the hepatic gluconeogenesis?
fructose1,6 bisphosphotase
what inhibits fructose 1,6 bisphosphotase?
AMP and fructose 2,6-bisphosphotase
what does high AMP levels signal?
low ATP levels so we do not need gluconeogenesis, instead we need to reserve energy for other liver functions and even perform glycolysis to generate ATP
can low ATP levels cause liver damage?
yes, high ATP levels are always high in the liver, so this could indicate liver damage(low ATP levels and can not do gluconeogenesis so glycolysis kicks in to make more ATP)
what does phosphofructokinase 2 do?
activates glycoylsis by activating fructose 2,6 bisphosphate which helps activate PFK1
which part of the bifunctional enzyme is activated when ther are high levels of insulin?
PFK1
during fasting and low insulin levels, what happens to muscle protein?
muscle protein is degraded and more alanine is released by muscle and activated the alanine glucose cycle in the liver
what is glycerol kinase?
Glycerol kinase is a phosphotransferase enzyme involved in triglycerides and glycerophospholipids synthesis. Glycerol kinase catalyzes the transfer of a phosphate from ATP to glycerol thus forming glycerol phosphate (ATP + glycerol ADP + sn-glycerol 3-phosphate).
what is the energy requirment for gluconeogenesis?
from 2 pyruvates.. you need 4 ATP and 2 GTP in additon 2 NADH are used
what is taken up in the blood during the fasting state?
alanine, glutamine, lactate, glycerol, free fatty acids
when there is a uptake of fatty acids and beta oxidation what is formed?
acetyl CoA and generate energy in the form of NADH and FADH2 from the ETC=energy
what does pyruvate carboxylase need as an activator?
acetyl CoA
when insulin dephosphorylates and enzyme or molecule will the enzyme be active or inactive?
the enzyme is activated and vice versa for glucagon
what does cyclic dependent AMP proetin kinase A do?
it affects the bifunction enzyme by phosphorylation( insulin does not like phosphates so it does not like protein kinase A) and cutting off PFK2 which activates glyclyisis and turns on Fructose 2,-bisphosphotase which promotes gluconeogenesis
what does phosphoprotein phosphotase favor?
it favors insulin(dephosphorylation) and activated PFK2 by cleaving the phosphate group and activating it
when PFK2 is on what will elevate in concentration?
fructose 2,6 nisphosphate which increase glycolysis
when fructose bisphosphotase 2 is activated what happens to glycolysis?
it does not happen, gluconeogenesis happens
T/F beta oxidation of fatty acids has to be going on when gluconeogenesis is occuring?
true
