Week 8 - Unit 2 Flashcards
What is the fate of glucose after a meal?
- Oxidized for energy in Glycolysis
- Synthesis of many compounds
- Storage as Glycogen or Triglycerides
What is the fate of Amino acids after a meal ?
- Protein synthesis
- Oxidation for energy
- Synthesis of nitrogen-containing compounds (nucleotides)
What is the fate of Fats after a meal?
- Storage- triglycerides
- Oxidation for energy
- Synthesis of membrane lipids
What are the dietary fuels?
Carbohydrates
Fat
Protein
Insulin will initiate cascade of events , anabolic processes of _______ fuels , and _____.
Storing
Growing
As levels of blood fuels decreases, you will see elevated levels of stress hormones ___, _____, and ______.
Cortisol
Glucagon
Epinephrine
The primary role of Cortisol, Glucagon, and Epinephrine is to initiate _____ processes to maintain a pool of fuel for cell functioning.
Catabolic - break down of stored fuels to release into bloodstream
Glucose is taken up by the Beta- cell in the pancreas via the _______ transporter. It is then ____ and increases levels of _____.
Glut-2 transporter
Oxidized
ATP
Increased levels of ATP in the Beta-Cells of pancreas (caused by Glucose entering cell), will cause the _____ ____ to close, causing decrease in the voltage in the cell, then opening the _____ channel.
Potassium channel
Calcium channel
Increase in calcium in Beta-cell will facilitate the packaging of _______ and the movement of it in _______ so it can be delivered to peripheral tissues.
Insulin (endocrine hormone)
Exocytosis
Insulin is initially translated as a _______ and requires cleavage of the _____ before it is active polypeptide.
Pro-protein
C-Peptide (2 cleavage locations)
The insulin protein, after the C-peptide is cleaved , consists of an ____ chain and a ____ chain that is linked by _____ linkages.
Alpha
Beta
Disulfide
What does Insulin bind in the target cells ?
what does it initiate ?
Tyrosine-kinase family
Initiates MAP-kinase cascade
when glucose is taken up by the liver, insulin will activate ______ production, fatty acid _____ and increase protein _____.
Glycogen
Synthesis
Synthesis
What will glucose paired with insulin activate in the skeletal muscle ?
Glycogen synthesis
Protein synthesis
What can high levels of insulin caused by blood glucose do in the adipocytes?
Synthesis of Triglycerides
When we synthesis Triglycerides or Glycogen we will at the same time ____ release of free fatty acids or release of free glucose.
Inhibit
When blood glucose is low what two main regions are stimulated?
- Brain- Hypothalamic regulatory center
2. Alpha cells of pancreas (release glucagon)
The pituitary gland in the hypothalamic regulatory center will secrete _______ during low blood glucose levels.
Adrenocorticotropic hormone (ACTH)
What does ACTH stand for ?
Adrenocorticotropic hormone
What does ACTH act on ?
Adrenal gland
- activates cortex (Cortisol release)
- activates medulla (Epinephrine release)
Where does Cortisol get released from ?
Adrenal gland Cortex
Where does Epinephrine get released from ?
Adrenal gland - Medulla
Glucagon binds a _____ receptor and then activates ______ as its second messenger.
G-coupled protein
cyclic AMP
The cAMP in the Glucagon cascade will activate ____ ____ A and elicit a cellular response.
Protein Kinase A
What do high levels of glucagon do to liver?
Glycogenolysis - catabolism of glycogen to free glucose
What do high levels of Cortisol do to the Skeletal muscle ?
Stimulate Protein catabolism so that AA can be delivered to Liver for gluconeogenesis to make more glucose
What does epinephrine do to the adipocytes?
Activates enzyme so that free fatty acids are released
What is the difference between Epinephrine and Norepinephrine at the chemical level?
-epinephrine has a Methyl group attached to its amine group, norepinephrine does not
Epinephrine will stimulate glycogenolysis in the skeletal muscle during exercise breaking it down to ______ to then make either acetyl CoA or Lactate depending on aerobic or anaerobic exercise.
Glucose
The primary responsibility of the liver is to provide _____ so the brain always has energy.
Glucose
The adipocyte will catabolize fat, and the fatty acids can be used in Skeletal muscle to make ATP or sent to liver who will make it into _____ ____ that can be used for energy by the brain.
Ketone bodies
In high blood glucose conditions, with insulin present , the liver is completing what functions
- Triglyceride synthesis
- Glycogen synthesis
- Active glycolysis
In low blood glucose conditions, the liver is completing what functions?
- Glycogen degradation
- Gluconeogenesis
(Glucagon and Epinephrine are present and glucose is released ) -Catabolic
Dietary fats are packaged into _______ that consist of fatty acids and glycerol after absorption in the GI and can be stored in Adipose tissue.
Chylomicrons
What functions to promote fuel storage after a meal and promotes growth?
Insulin
What activates gluconeogenesis and glycogenolysis (liver) during fasting and activates fatty acid release from adipose tissue ?
Glucagon (mobilizes fuels)
What will mobilize fuel during acute stress ?
Epinephrine
What will provide for changing requirements over the long term (steroid hormone)?
Cortisol
Where does digestion begin ?
In mouth with salivary amylase- then inactivated in stomach by pH
When food enters the intestine after the stomach , what will re-add salivary amylase?
Pancreas
What are polysaccharides broken down into in the stomach ?
Alpha-Dextrins
how does salivary amylase digest polysaccharides ?
hydrolyzes the internal Alpha-1-4 bonds to make Disaccharides and Oligosaccharides
What are the primary Disaccharides ?
Lactose
Maltose
Trehalose
What is Lactose made from?
Galactose and Glucose
What is Trehalose made from?
Glucose + Glucose
Once the monosaccharides are in their singular form, they are transported from the lumen into the capillaries via :
Secondary Active transport
What is the first step/ first regulated step of Glycolysis ?
Phosphorylation of Glucose into Glucose 6-P
- by Hexokinase
- or by Glucokinase (liver)
True or False:
The phosphorylation of glucose is reversible and it is not trapped in the cell.
False- the phosphorylation is irreversible and it is trapped in cell once phosphorylated
What are the four main fates of Glucose after it has been phosphorylated into Glucose 6-P ?
Glycolysis
Glycogen synthesis
Pentose phosphate pathway
“Other pathways”
What happens in Glycolysis after Glucose is phosphorylated ?
Glucose 6-P is isomerized by phosphoglucoisomerase
-to Fructose 6-phosphate
What happens after you have the Fructose 6-phosphate in Glycolysis ?
Fructose 6-P is phosphorylated by phosphofructokinase (enzyme), second ATP is used for this
What does Fructose 6-P turn into after it is acted on by phosphofructokinase?
Fructose 1,6 -bisphosphate (phosphate groups on opposite ends)
What is the next enzyme to act on Fructose 1,6 bisphosphate ?
Aldolase - cleaves the 6 C chain inhalf to make 2 products
What two products will Aldolase make when it cuts Fructose 1,6-bisphosphate in half?
- Dehydroxyacetone phosphate
2. Glyceraldehyde3-phosphate
What is the enzyme that can catalyze the reversible changing between Dihydroxyacetone phosphate and Glyceraldehyde 3-phosphate
Triosephosphate isomerase
What will produce the first NADH in glycolysis ?
Enzyme glyceraldehyde 3-P dehydrogenase is used in Dehydrogenation reaction on Glyceraldehyde 3-P (removes H+)
What is the oxidation of glyceraldehyde 3-P dependent upon?
A cysteine residue in the active site of the enzyme - allowing a high energy thio-ester bond- intermediate will accept free phosphate and donate H to NAD
What is the next product in glycolysis after Glyceraldehyde 3-Phosphate?
1,3 Bisphosphoglycerate (has 2 phosphate groups)
What is 1,3-Bisphosphogylcerate used for in Glycolysis ?
Donates phosphate to ADP to make ATP (2 total per one glucose molecule)
What happens to 1,3 bisphosphoglycerate after it is acted upon by phosphoglycerate kinase ?
Turns into 3-phosphoglycerate
What does 3-phosphoglycerate get acted upon by ? what does it turn into?
Phosphoglycerate mutase (enzyme moves the phosphate group) = 2-Phosphogylcerate
What is the last high energy intermediate in Glycolysis that is used to make ATP?
Phosphophenol pyruvate (P- is on middle C)
How do you get Phosphophenol pyruvate ?
Removal of H2O from 2-phosphoglycerate (OH- off of the 3 carbon)
What is the first high energy intermediate used to make ATP in glycolysis ?
1,3-Bisphosphoglycerate
What does Phosphophenol pyruvate turn into after it loses its Phosphate to make ATP?
Pyruvate
What type of reaction occurs between the high energy intermediates of glycolysis to make ATP at the end of the process?
Substrate level phosphorylation
For every One glucose you can make ___ Pyruvate , ____ NADH, and ___ ATP net total. (2 ATP are used up in beginning.
2
2
2
What is the overall Delta G of Glycolysis ?
- 22kg/M
- very powerful resisting reverse direction without input of energy to reverse it
What are the two primary fates of pyruvate?
- Aerobic glycolysis it is accepted by TCA cycle and turned into Acetyl CoA
- Anaerobic glycolysis - reduced to Lactate by Lactate dehydrogenase
What does Lactate Dehydrogenase do ?
reduces Pyruvate (adds 2 H) to make Lactate (acid)
- NADH is donating the H
- reversible
- used in anaerobic conditions
What are the two phosphorylated molecules in glycolysis with high phosphate transfer potential?
1,3-Bisphosphoglycerate
Phosphophenolpyruvate
What 3 primary places is Glycolysis regulated at ?
- Hexokinase or Glucokinase (enzymes)
- Phosphofructokinase-1 (enzyme)
- Pyruvate Kinase (enzyme)
Regulation of Hexo or glucokinase is regulated by ?
Product - Glucose-6-P (elevated levels)
or
Glucokinase is also regulated by regulatory protein that binds it and will release it in the presence of Glucose or Fructose-1 phosphate so it can be active
What is phosphofructokinase-1 (enzyme)activated /enhanced by
- high levels of AMP
2. Fructose 2,6 bisphosphate
What can inhibit phosphofructokinase-1 (enzyme ?
- ATP
2. Citrate
Where does Fructose 2,6 phosphate come from? is it part of glycolysis ?
Not part of glycolysis
- Fructose 6-P is phosphorylated into F 2,6-P by Phosphofructokinase 2
- it will be a precursor that enhances phosphofructokinase -1 activity
Fructose 2,6 Bisphosphate is a ______ to the enzyme Phosphofructokinase-1 that is used to make Fructose 1,6 bisphosphate in glycolysis.
stimulator
Phosphofructokinase 2 is a _____ enzyme with two domains. It has 2 domains Kinase domain and phosphatase domain.
Bifunctional enzyme
What are the two domains of phosphofructokinase 2 ?
- Kinase domain (PFK2)
2. Phosphatase domain (FBP2)
What does the kinase domain do in the phosphofructokinase 2 ?
it will add free phosphate to Fructose 6-Phosphate to make Fructose 2,6, bisphosphate (stimulating product for phosphofructokinase 1 enzyme in glycolysis)
What does the phosphatase domain on Phosphofructokinase 2 do ?
Removes phosphate from Fructose 2,6 bisphosphate
- used in gluconeogenesis
What is Citrate ? how does it inhibit Glycolysis
intermediate of TCA cycle that is transported out of mitochondria into cytosol
-accumulation will block oxidation of glucose in cytosol
What enzyme does accumulation of citrate inhibit?
phosphofructokinase-1
What will stimulate Pyruvate Kinase?
- Fructose 1,6, bisphosphate (upper product of pathway stimulating lower part of pathway)
What will inhibit pyruvate kinase?
ATP
What can 2,3 bisphosphoglycerate function as ?
regulator of hemoglobin -influences binding of oxygen to hemoglobin
Acetyle CoA (within mitochondira) can be used to synthesis alternatively to make ________.
Fatty acids
Glucose 6-Phosphate can be converted to Glycerol-P (3 carbon molecule) used as backbone in _______ which combines 3 fatty acids and one glycerol molecule.
Triglycerides
When Fructose 2,6 phosphate levels are elevated in the cell, what is true for the cell?
- Glucose levels are high
- PFK 1 will be activated
- Pyruvate kinase will be activated (PFK1 stimulates this)
- NADH production is increased
Where can glycogen synthesis occur?
Muscle and Liver
What is the role of glycogen in muscle?
Is Glucose 6-P from muscle ever released into circulation?
produced and released for muscle itself under anaerobic conditions (makes CO2 and lactate)
-never released into circulation
What enzyme does the muscle lack so that Glucose 6-P can not leave the muscle cells to enter circulation as free glucose?
Glucose 6-phosphatase (would remove required phosphate group that allows glucose to leave cells)
What allows the glucose to be released from the liver to maintain blood levels?
Glucose 6-phosphatase (removes the phosphate group from glucose)
In Glycogen synthesis what enzyme will act to convert Glucose 6-Phosphate into Glucose 1-Phosphate ?
Is it reversible and used in the opposite direction for degradation?
Phosphoglucomutase
-Yes it is reversible and used in synthesis and degradation
Glycogen synthesis is an energy requiring pathway, it will use ____ to be charged.
UTP
What enzyme will charge Glucose 1-P to make UDP-Glucose in the glycogen synthesis pathway ?
UDP-glucose pyrophosphorylase
uses UTP as substrate
UDP-Glucose is added to preexisting _______ molecules that usually consist of several branch points in glycogen synthesis.
Glycogen
What are the 2 enzymes for the reaction that will add UDP-Glucose to branch points on existing glycogen molecules?
Glycogen synthase
4,6 Transferase (branching enzyme)- moves the attached molecule around on chain
True or False:
UDP is not regenerated in the degradation of glycogen because the synthesis is an energy requiring pathway.
True
What is the primary degradation enzyme in glycogen degradation
Glycogen phosphorylase
What are the 3 enzymes needed in glycogen degradation in order?
- Debrancher enzyme
- Glycogen phosphorylase
- Glucose-6 phosphatase (only in liver- so glucose can leave cell)
What 2 enzymes are used to add molecules to Glycogen?
Glycogen synthase
4,6 Transferase
the branch points on the Glycogen core are held together by ?
Glucose reside and alpha-1,6 linkage
On the branch chains, the molecules are added and held together by /
Glucose residue and alpha 1,4 linkage
- once a certain length the 4,6 transferase will move remove the extended chain and use alpha 1-6 linkage again on core
what does 4,6 transferase do in glycogen synthesis?
it will remove the extended chain from glycogen, then move a portion of the chain to core with alpha 1-6 linkage to make branches (more room on all nonreducing ends of sugars)
In glycogen degradation, Glycogen phosphorylase will free glucose from chains by addition of ____ _____. This will generate ________.
Free phosphate
Glucose 1-phosphate
Glycogen phosphoryalse activity is constrained when…..
the glycogen chain is shortened near a branch point.
What will the 4:4 transferase do in glycogen degradation when the branch chain becomes too short for Glycogen phosphorylase to act on it?
remove the Alpha 1-6 glucose residue linkage
move it to be incorporated into the Glycogen core
After the Transferase 4:4 moves the short chain to be incorporated into the core, what enzyme can act to remove one glucose molecule that is left on branch point?
Alpha-1,6 Glucosidase
Glycogen phosphorylase and Glycogen synthase are heavily regulated so that ?
Synthesis and degradation of glycogen is not occurring at the same time
How is Glycogen phosphorylase and Glycogen synthase regulated?
through phosphorylation and dephosphorylation reactions to activate and inactive (they are opposite eachother)
When you phosphorylate Glycogen phosphorylase is it active or inactive ?
Active
When you phosphorylate Glycogen synthase is it active or inactive?
Inactive
If there is no phosphate attached to the Glycogen phosphorylase enzyme, is it active or inactive?
inactive
_____ and _____ will stimulate Glycogenolysis (glycogen degradation)
- Glucagon (liver)- no impact on muslce
2. Epinephrine (muscle and liver)
_____ will stimulate glycogen synthesis in the muscle and liver
Insulin
Glucagon and epinephrine will bind to a _______ on the cell membrane.
G-coupled protein
-family of heteromeric proteins associated
G proteins after being activated by Glucagon or Epinephrine will detach and bind GTP to activate?
Adenylate cyclase (in membrane) -Converts ATP into cAMP
cAMP will be a second messenger (in glucagon and epinephrine pathway) and will bind ________ when it is inactive to make the active form.
Protein Kinase A
Protein kinase A will regulate _______ by adding a phosphate to inactivate it, and ____ by adding a phosphate to activate it.
Glycogen synthase (inactivates)
Glycogen phosphorylase (activates)
Protein Kinase A will function to phosphorylate Phosphorylase kinase to make it active (added P to it), which will then phosphorylate _______ into its active form.
Glycogen phosphorylase (B)
- active when phosphorylated
- used in glycogen degradation pathway to add free phosphate to glucose molecules to make Glucose 1-P off of glycogen
Protein kinase A will take Phosphate from ATP to add a P to ______ to inactivate it.
Glycogen Synthase
What is the secondary (besides the G-protein) receptor that epinephrine can bind on the liver
Alpha-agonist receptor (has its own G-protein associated receptor)
What will binding the alpha-agonist receptor (has its own G-protein associated receptor) do when epinephrine binds it in the liver?
will increase glycogen degradation - through manner that is Calcium regulated
In the cascade with the alpha agonist receptor that epinephrine binds to in the liver after the G-protein that is associated with the agonist receptor is activated?
It will bind and activate Phospholipase C
that will facilitate cleavage of PIP(2) into IP3 and DAG
What does Diacylglycerol (DAG) do once activated by the cleavage of PIP by Phospholipase C?
Stimulate activity of protein kinase C- will phosphorylate the Glycogen synthase then inactivating it
What will the Inositol-Phosphate 3 (IP3) do once it is activated by cleavage of the PIP2 in the membrane by active phospholipase C ?
IP3 will stimulate release of Ca+ from the Endoplasmic reticulum
- then will bind Ca+ calmodulin binding protein that leads to inactivating Glycogen synthase and activating Glycogen phosphorylase
What does Ca+ calmodulin do once Ca+ that was released from the ER by Inositol-phosphate 3 activation ? it has 2 effects….
- activation of Calmodulin-dependent protein kinase ( inactivates glycogen synthase)
- activation of Phosphorylase kinase (inactivates glycogen synthase and activates glycogen phosphorylase)
What can Calmodulin dependend protein kinase do once activated by Ca+calmodulin
phosphorylate the Glycogen synthase which inactivates it
What can Phosphorylase kinase do once it is activated by Ca+calmodulin ?
Phosphorylate the Glycogen phosphorylase to then activate it
- will phosphorylate Glycogen Synthase to inactive it at the same time
Glycogen synthase has different sites for the different enzymes that can phosphorylate it to inactivate it, what are the 3 enzymes that can do this?
- Protein kinase C (from DAG)
- Calmodulin-dependent protein kinase
- Phosphorylase kinase
Glycogen synthesis is primarily controlled by _______ in the muscle.
exercise
Primary metabolism of glycogen in muscle will lead to production of _____ for use in anaerobic exercise.
Glucose -1 P- then leads to lactic acid
Cascade in skeletal muscle with Epinephrine binding G-protein, leading to cAMP activating _____. this then leads to phosphorylating _______ then phosphorylating _______ to activate it.
Protein kinase A (same as in liver)
Phosphorylase kinase
Glycogen phosphorylase a (degradation)
What are the two ways Glycogen degradation can be stimulated in muscle?
- Epinephrine binding to G-protein receptors leading to activation of Protein kinase A
or - Nerve impulse leading to Ca+ release from ER then Ca+calmodulin activation
(both will converge at phosphorylating phosphorylase kinase that then phosphorylates Glycogen phosphorylase a)
What is an allosteric activator of Glycogen phosphorylase b (degradation) in the muscle?
Muscle contraction
- high levels of AMP will be allosteric activator (=high levels of muscle contraction)
- independent of phosphorylation cascades
- ensures the muscle can support itself during exercise
In the Liver, during a fasting state, what is happening to glucagon, insulin, cAMP (regulators) ?
what is happening to glycogen degradation and synthesis (tissue response)?
- Glucagon = increased
- Insulin = decreased
- cAMP = increased
degradation = increased synthesis = decreased
In the liver, after a carbohydrate meal, what is happening to glucagon, insulin, cAMP and glucose levels (regulators)?
what is happening to glycogen degradation and synthesis (tissue response) ?
Glucagon = decreased
Insulin = increased
Glucose = increased
Tissue cAMP = decreased
degradation = decreased synthesis = increased
In the liver, after exercise and stress, what is happening to Blood epinephrine, tissue cAMP, and Ca+calmodulin levels (regulators) ?
degradation and synthesis of glycogen?
Blood epinephrine = increased
Tissue cAMP = increased
Ca+calmodulin = increased
degradation = increased synthesis = decreased
In the muscle, what is happening during fasting (rest) with blood insulin levels ?
Glycogen synthesis and Glucose transport?
Blood:insulin - decreased
Synthesis = decreased Transport = decreased
What happens in muscle after a carbohydrate meal to blood insulin regulator?
Glycogen synthesis ?
Glucose transport?
Blood insulin = increased
Glycogen synthesis = increased
Glucose transport = increased
What happens in the Muscle after Exercise to regluators: blood epinephrine, tissue AMP, Ca+calmodulin, and cAMP?
Glycogen synthesis and degradation?
Glycolysis?
Blood epinephrine = increased
Tissue AMP = decreased
Ca+calmodulin = increased
cAMP = increased
Glycogen synthesis = decreased
Glycogen degradation = decreased
Glycolysis = increased
Insulin stimulates all of the following pathways except:
- Glycolysis
- Amino Acid catabolism
- Glycogen synthesis
- Fatty acid synthesis
- Amino acid catabolism
- Insulin is an anabolic hormone that facilitates synthesis
- Cortisol is responsible for mobilization of AA from muscle
Insulin stimulates fatty acid synthesis in liver. These fatty acids are transported to the adipose tissue as:
VLDL particles
The release of insulin from the pancreatic Beta-Cells is mediated by which of the following processes:
- Decrease in blood glucose
- Increase in glucagon
- Increase in intracellular calcium
- Increase in intracellular calcium
Von Gierkes disease is a glucogen storage disease of which area?
Which area is McArdles disease ?
- Storage in liver
2. Storage in skeletal muscle
When glucagon is elevated what is true for McArdles patients only and not Von Gierke’s disease patients?
Patient will fatigue easily during exercise - they can not store glycogen
What three things occur for Von gierkes disease patients (glucogen storage deficent in liver) when glucagon is elevated?
- Patient will present with lactic acidemia
- Patient will become hypoglycemic after a fast
- Patient will have elevated fructose 2,6 phosphate levels
What is absent in patients with McArdles disease?
Glycogen synthase in Skeletal Muscle
- Glycolysis is reduced
- ATP levels reduced
What is absent in Von Gierkes disease patients in the liver?
Glucose 6-phosphatase is missing
- Glucose 6-P can not be converted into usable Glucose
- increases flux of glycolysis so that overflow goes into lactate production and TCA cycle as Acetly coA
What compound allosterically activates phosphofructokinase 1?
Fructose 2,6 bisphosphate
What is an insulin insensitive GLUT transported found primarily on the liver?
GLUT2 transporter
The isozyme of Hexokinase called Glucokinase that is found in the ______ and Beta cells of the _______ has a much ______ Km than other hexokinases.
liver
pancreas
higher
______ will irreversibly commit Glucose-6 Phosphate to the glycolytic pathway. It converts Fructose 6-P to Fructose 1,6 bisphosphate (adds P using ATP).
Phosphofructokinase-1 (PFK-1)
What molecule is cleaved by Aldolase to make the set of 2 3 carbon molecules in glycolysis ?
Fructose 1,6 bisphosphate
The oxidation of Glyceraldehyde 3-P by Gyceraldehyde 3-p dehydrogenase is dependent on a ____ residue at the active site of the enzyme which forms a high energy _____ bond during the course of the reaction. NAD+ will change to NADH
Cysteine
thioester
Glyceraldehyde 3-P is dehydrogenated and then its high energy intermediate will accept an inorganic phosphate to form the high energy acyl phosphate bond making _________. This is the start of substrate level phosphorylation.
1,3-bisphosphoglycerate
What will transfer the P from 1,3-bisphosphoglycerate to ADP?
Phosphoglycerate kinase
- next product is then 3-phosphoglycerate
What are the two ways that NADH is oxidized to make sure it is in supply for use in the dehydrogenation of glyceraldehyde 3-P?
- Aerobic- shuttling the H across the mitochondrial membrane
- Anaerobic- Lactate Dehydrogenase will reduce pyruvate to lactate and take H from NADH
What are the two main shuttles that can transport the H across the mitochondrial membrane ?
Glycerol 3-P shuttle
Malate-aspartate shuttle
In the Glycerol 3-P shuttle, what are the Electrons from NADH dropped of on inside the mitochondria?
FAD will pick them up and then take them to CoQ in the ETC
In the glycerol 3-P shuttle what is precursor to Glycerol 3-P before it picks up H from NADH?
Dihydroxyacetone -P
In the Malate-aspartate shuttle, what does the NADH need to drop its H off on and converts it to what for transport across the membrane?
Drops the H on Oxaloacetate that changes it to Malate
Malate crosses then drops of H to NAD
If the NADH is oxidized by the Glycerol-3-P shuttle what is the production of ATP?
What if its oxidized by the Malate-aspartate shuttle?
Glycerol 3-P = 1.5 mol of ATP per mol of NADH
Malate-Aspar = 2.5 mol of ATP per mol of NADH
thus the 2 NADH in glycolysis can lead to 3-5 ATP
How many ATP can each mol of Pyruvate give in aerobic glycolysis ?
12.5
How many mol of ATP can be produced from 1 mol of glucose when it is fully oxidized to CO2?
30 to 32
12.5- per pyruvate
3-5 for NADH
2 from Glycolysis
What two AA can the Glycolytic pathway produce?
Alanine
Serine
The liver synthesizes fatty acids from the ______ generated by glycolysis .
Pyruvate
The liver also functions as a reversal of glycolysis synthesizing glucose from ______, _____, and ______.
Lactate
Glycerol 3-P
AA
Red blood cells form _______ to serve as an allosteric inhibitor of oxygen binding to heme. Most cells only need very small amounts of it as it is not depleted.
2,3 bisphosphoglycerate
What are the three enzymes in glycolysis that are inhibited by feedback inhibition due to high levels of ATP ?
- Phosphofructokinase-1 (PFK-1)
- Pyruvate Kinase (only for liver-inhibits glycolysis if gluconeogenesis is occurring)
- Pyruvate Dehydrogenase (converts pyruvate to AcetylCoA)
The activity of ____ _____ in the mitochondrion determines whether pyruvate is converted to lactate or to acetyl coA in the Mitochondria for TCA cycle.
Pyruvate dehydrogenase
What does the higher Km of glucokinase in the liver allow for ?
its own product Glucose-6 P is less likely to inhibit the pathway allowing glycolysis to continue in liver even when energy levels are high - in other tissues with Hexokinase (lower km) its own product will inhibit it much faster
PFK-1 is an ______ enzyme that has a total of six binding sites: two are for substrates, and four are allosterically regulated sites.
Allosteric
rate limiting enzyme of Glycolysis
what are two allosteric activators of PFK-1 ?
AMP and Fructose 2,6-bisphosphate (opposes ATP inhibition)
True or False:
Fructose 2,6-bisP is an intermediate of Glycolysis
False
- it is an allosteric activator of PFK-1
- synthesized by PFK-2
In skeletal muscle, high concentrations of Fructose-6 P activate the kinase and inhibit the phosphatase, thereby increasing the concentration of fructose 2,6-bisP and ____ ______.
activating glycolysis
What can PFK-2 be regulated by ?
Ratio of activation of kinase vs phosphatase domain
- phosphorylation by serine-threonine protein kinases
- cAMP-dependent protein kinase (protein kinase A) will deactivate PFK-2 due to circulating levels of glucagon during fasting states
What can inhibit Pyruvate Dehydrogenase ?
Increased levels of NADH
Increased levels of its own product-acetyl CoA
What is an activator of pyruvate dehydrogenase?
increased ADP
Increased Ca+
What is the bond on glycogen between the core glucose molecules?
alpha-1,4 glycosidic bonds
What is the bond on glycogen between the core and a branch?
alpha 1,6 (branches every 8 to 10 residues)
What is Glycogen degraded to ?
Glucose 1-P then Glucose 6-P then it has several different paths it can go , only in liver is Glucose 6-phosphatase avaliable to export glucose to blood
What is the general path of glycogen synthesis ?
Glucose to Glucose 6-P to Glucose 1-P to UDP-Glucose (can go to other pathways from here ) or Glycogen synthase can make this into Glycogen
What is the first and then second enzyme in glycogen degredation?
- Debrancher enzyme
2. Glycogen phosphorylase
What does Glycogen phosphorylase do ?
changes glycogen into Glucose 1-P
What does Phosphoglucomutase do ?
Can either make Glucose 1-P into Glucose 6-P or do the reverse
Glycogen degradation is a ______ reaction (breaking of a bond using a phosphate ion as a nucleophile)
Phosphorolysis
What membrane bound enzyme will degrade cAMP rapidly back to AMP?
Phosphodiesterase
What sequence of enzymes allows for the synthesis of glycogen from glucose 6-P
- Phosphoglucomutase
- UDP-glucose pyrophosphorylase
- Glycogen synthase
- amylo-(1,4a1,6)-transflycosylase
What intermediate is an allosteric activator of pyruvate Kinase?
Fructose 1,6-bisphosphate
During the fasted state (glucagon is high), what is the state of glycogen phosphorylase and glycogen synthase
both are phosphorylated
-only the glycogen phosphorlyase is active
Epinephrine acting on beta receptors on liver, transmit signals through ____ to adenylate cyclase,which increases _____ levels and activate PKA.
G Proteins
cAMP
Epinephrine acting at Alpha receptors on hepatocytes will inhibit glycogen synthesis primarily by ….
increasing levels of Ca+ mediated by PIP2 -Ca+ transduction system through Phospholipase C
What cells release Insulin?
Pancreatic Beta cells
To release Insulin, pancreatic beta cells will have a change in intracellular glucose which increases ATP. Increased ATP will ______ K+ release .
Inhibit
Inhibiting K+ release after ATP increases in the Beta pancreatic cells, will _____ the cell.
Depolarize
Depolarizing the Beta pancreatic cell will ________ intracellular Ca+ which facilitates exocytosis of ______.
increase
Insulin
Insulin enhances what three synthesis processes in the liver?
Glycogen synthesis
Fatty acid synthesis
Protein synthesis
Insulin enhances what two processes in the Adipose?
Triacylclyerol synthesis
Glucose uptake through GLUT4
Insulin enhances what two processes through Skeletal muscle?
Glucose uptake through GLUT4
Protein synthesis
Where is the GLUT 2 transporter mainly found?
Liver- high capacity for Glucose but low affinity
What cells release Glucagon in response to low blood glucose?
Pancreatic Alpha cells
What does Glucagon enhance in the liver?
Glycogenolysis
Gluconeogenesis (AA substrates)
Oxidation of fatty acids
What does glucagon enhance in the adipose?
Lipolysis
What does glucagon enhance in the skeletal muscle?
no impact
Epinephrine signals through ________ in the liver or the ______ in skeletal muslce.
Alpha agonist receptor (liver)
GPCR (skeletal muscle)
What effect does epinephrine have on the Liver?
- Glycogenolysis (increase of Phospholipase C, Ca+ and inhibits Glucagen synthesis)
- Oxidation of fatty acids (generation of ketones)
What does epinephrine do to the adipose?
lipolysis
what does epinephrine act through and cause in the skeletal muslce?
Glycogenolysis
-through cAMP pathway
Cortisol will bind an intracellular receptor and mediate changes through _____ ______.
transcriptional regulation
In skeletal muscle, cortisol will promote ______ _____ to provide AA for _______ occuring in the liver.
Protein catabolism
Gluconeogenesis
What are the primary Monosaccharides?
Glucose
Galactose
Fructose
What are the primary Disaccharides?
Trehalose (2 glucose)
Lactose
Sucrose
When Phosphofructokinase 2 is dephosphorylated, it is _____.
Active
What 2 steps in Glycolysis will use ATP for cofactor?
- Hexokinase or Glucokinse uses it - creation of Glucose 6P
2. Phosphofructokinase-1 uses it to make Fructose 1,6 bisphosphate
Elevated AMP will allosterically activate _____ _______.
Glycogen phosphorylase B
