Chapter 8: Carbohydrate Metabolism Flashcards
What is glycolysis??
- process of converting glucose to two molecules of pyruvate capturing a small amount of energy
What is glycogenesis?
when glycogen ( a storage form) is formed when glucose levels are really high
What is glycogenolysis ?
when glycogen is degraded forming glucose for when glucose levels are very low.
What is gluconeogenesis?
when glucose is synthesized from noncarbohydrate precursors by reactions.
What is the pentose phosphate pathway?
enables cells to convert glucose-6-phosphate a derivative of glucose to ribose-5-phosphate and other types of monosaccharides
When glucose molecules are not required for immediate energy production it is stored as what??
-glycogen in the liver and muscles
Glycolysis is an ____ process??
anaerobic process which would have been needed in an oxygen poor environment
The small amount of energy captured in glycolysis is temporarily stored where?
- ATP and NADH
Anaerobic organisms??
- those that do not use oxygen to generate energy
Pyruvate can be converted into waste products such as what? (3)
ethanol, lactic acid and acetic acid
Aerobic respiration??
when oxygen is sued as a terminal electron acceptor….via completely oxidizing pyruvate to form CO2 and H2O in an elaborate stepwise mech.
Glycolysis consists of how many reactions and stages?
- 10 reactions
- 2 stages
Do a brief overview of what happens in each stage of glycolysis?
- Glucose —-> Glyceraldehyde-3-phosphate..consuming two ATP
- Glyceraldehyde-3-phosphate—-> 2 pyruvates
L> 4 ATP and 2 NADH
L> technically the net gain of ATP is actually 2
What is the net equation for glycolysis?
D-Glucose + 2 ADP + 2Pi + 2NAD+ —–> 2 pyruvate + 2 ATP + 2 NADH + 2H+ + 2H2O
What occurs in reaction one for glycolysis?
Glucose —> Glucose-6-phosphate
- 1 ATP in and 1 ADP via hexokinase and Mg 2+
What occurs in reaction two for glycolysis?
Glucose-6-phosphate fructose-6-phosphate
L> via phosphoglucoiosmerase
What occurs in reaction three for glycolysis?
Fructose-6-phosphate——> Fructose-1,6-bisphosphate
L> via PKF-1 ( phosphofructokinase-1)
L>One ATP in and one ADP out
What occurs in reaction four for glycolysis?
Fructose-1,6-bisphosphate Dihydroxyacetone phosphate (DHAP) + Glyceraldehyde-3-phosphate
L> via aldolase
What occurs in reaction five for glycolysis?
—> DHAP Glyceraldehyde-3-phosphate via triose phosphate isomerase
What occurs in reaction six for glycolysis?
Glyceraldehyde-3-phosphate Glycerate-1,3-bisphosphate
L> via glyceraldehyde-3-phosphate dehydrogenase
L> Pi+ NAD+ in and NADH + H+ out
What occurs in reaction seven for glycolysis?
Glycerate-1,3-bisphosphate glycerate-3-phosphate
L> via phosphoglycerate kinase
L> one ADP in and one ATP out
What occurs in reaction eight for glycolysis?
Glycerate-3-phosphate Glycerate-2-phosphate
L> via phosphoglycerate mutase
What occurs in reaction nine for glycolysis?
Glycerate-2-phosphate phosphoenolpyruvate (PEP)
L> enolase
(H2O out)
What occurs in reaction ten for glycolysis?
phosphoenolpyruvate ———-> Pyruvate
L>via pyruvate kinase
L> ADP in and ATP out
What are the products of glycolysis for one molecule of glucose?
2 ATP, 2 NADH, 2 Pyruvate
Under aerobic conditions what happens to pyruvate?
- it is converted into acetyl-CoA, which is the entry level for the citric acid cycle.
L> which is an amphibolic pathway which completely oxidizes 2 carbons to form CO2 and NADH and FADH2
The electron transport system??
a series of oxidation reduction reactions, transfers electrons from NADH and FADH2 to O2 to form water. The energy that is released during ETC is coupled to a mechanism that synthesizes ATP
Under anaerobic conditions what happens to pyruvate?
- further oxidation of pyruvate is impeded.
L> compensated via converting it to a more reduced organic compound and regenerating the NAD + required for glycolysis to continue via fermentation
ex: muscle cells produce NAD + via pyruvate Lactate
In yeast what happens to pyruvate?
- decarboxylated to form acetaldehyde which is then reduced by NADH to form ethanol!
What three reactions in glycolysis have negative delta G values?
1, 3 and 10!
( catalyzed by hexokinase, PFK-1 and pyruvate kinase)
L> all of which are irreversible
What are the delta G values for the remaining reactions (2,4-9) in glycolysis?
- they are so close to zero that they operate near equilibrium.
L> therefore they are easily reversible; small changes in substrate or product concentrations can alter the direction of each reaction.
During gluconeogenesis which reactions does it bypass?
- it does not involve reactions 1, 3 and 10
L> therefore it does not involve those enzymes either…but it utilizes the rest of the glycolysis enzymes.
Glycolysis is regulated by what? (3)
- allosteric regulation of three enzymes : hexokinase, PFK-1 and pyruvate kinase.
L> the reactions catalyzed by these are irreversible and can be switched on and off by allosteric effectors
Glycolysis regulation:
What is hexokinase inhibited by?
- excess g-6-p
Glycolysis regulation:
- PFK-1 and pyruvate kinase are activated by what??
High AMP levels
indicator for low energy production
Glycolysis regulation:
What inhibits both PFK-1 and pyruvate kinase?
- high levels of ATP
Glycolysis regulation:
When ATP is in a high concentration citrate and acetyl-CoA accumulate and inhibit what?
- PFK-1 and pyruvate kinase
Glycolysis regulation:
Fructose-2,6-bisphosphate produced via hormone induced covalent modification of PFK-2 is an indicator of high levels of available glucose and allosterically activates what?
PFK-1
Glycolysis regulation:
Accumulation of fructose-1,6-bisphosphate activates what?
pyruvate kinase
Glycolysis is also regulated by what two hormones?
Glucagon and insulin
Glycogen released by pancreatic cells when blood glucose levels are low activates what?
the phosphatase function of PFK-2 …reducing the level of fructose-2,6-bisphoshate in the cell…..decreasing flux through glycolysis and activity of PFK-1
Glycolysis regulation:
Cyclic AMP?
- a second messenger produced from ATP in a reaction catalyzed by adenylate cyclase….it binds to and activates protein kinase A
Glycolysis regulation:
Insulin?
released from the pancreatic cells when blood glucose levels are high. ….activating kinase function of PFK-2 …increasing the level of fructose-2,6-bisphosphate…..increasing glycolysis activity.
Glycolysis regulation:
- Hexokinase activator and inhibitor?
- PFK-1 activator and inhibitor ?
- Pyruvate kinase activator and inhibitor?
- no activator, inhibitor: G-6-P, ATP
- activator: F-1,6-Bis and AMP, inhibitor: Citrate, ATP
- activator: F-1,6-Bis and AMP, inhibitor: Acetyl-CoA and ATP
What are the precursors involved in gluconeogenesis?
- lactate, pyruvate, glycerol and alpha-keto acids
The reaction sequence for gluconeogenesis is basically what?
- the reverse of glycolysis….but alternative reactions occur in place of the three irreversible reactions in glycolysis
Explain briefly the first reaction that is bypassed from glycolysis in gluconeogenesis?
1. Synthesis of PEP L> pyruvate + CO2 + H2O -------> Oxaloacetate + H+ L> ATP in and ADP and PI out (pyruvate carboxylase ..biotin) and then OAA PEP + CO2 - GTP in and GDP out (pep carboxykinase)
How is OAA transported across the mitochondrial membrane ?
- its impermeable to OAA
L> Malate shuttle
L> OAA is converted to Malate…..and then reversed to OAA once in the cytoplasm
Explain briefly the second reaction that is bypassed from glycolysis in gluconeogenesis?
conversion of f-1,6-bisp to f-6-phosphate
F-1,6-bisp + H2O ——-> f-6-p
( fructose-1,6-bisphosphase )
—- stimulated by citrate and inhibited by AMP and f-2,6-bisp
Explain briefly the third reaction that is bypassed from glycolysis in gluconeogenesis?
formation of glucose from g-6-p
Substrate cycle??
L> ex?
L> coordinately regulated?
- each set of paired reactions (ex: gluconeogenesis…each of the forgoing reactions is paired with an irreversible reaction)
- because they are coordinately regulated ( an activator of the enzyme catalyzing the forward reaction serves as an inhibitor of the enzyme catalyzing the reverse reaction.
Flux control??
regulation of the flow of substrate and removal of product…..it is more effective if transient accumulation of product is funnelled back through the cycle.
Compare glycolysis and gluconeogenesis in terms of ATP!
- glycolysis = energy generating
- gluconeogenesis = energy consuming
L> requires the hydrolysis of six high energy phosphate bonds instead of generating ATP
Gluconeogenesis substrates :
1. Lactate
- released by RBC’s
L> Cori cycle: lactate is released by skeletal muscles during exercise
L> reconverted to pyruvate via lacte dehydrogenase once in the liver ….then to glucose via gluconeogenesis
Gluconeogenesis substrates :
2.Glycerol
-product of fat metabolism in adipose tissue …transported to the liver…converted to glycerol-3-phosphate via glycerol kinase ….it undergoes oxidation to form DHAP in the cytoplasm when NAD+ is relatively high
Gluconeogenesis substrates :
3. Amino acids: Alanine
- aa’s converted into glycolytic intermediates
L> when exercising muscles produce large quantities of pyruvate
L> some of these molecules are converted to alanine
Pyruvate + L-Glutamate L-Alanine + alpha-Ketoglutarate
Gluconeogenesis substrates :
What happens to alanine once its been transported to the liver?
its reconverted into pyruvate and then glucose
Gluconeogenesis substrates :
3. cont..
Glucose-alanine cycle
- recycles alpha keto acids btwn muscle and liver
- transports amino nitrogen to the liver..
L> once alanine reaches the liver and is converted back into pyruvate the amino nitrogen is incorporated into urea.
Gluconeogenesis Regulation:
- what three ways is it primarily regulated?
- substrate availability, allosteric effectors and hormones
Gluconeogenesis Regulation:
- It is stimulated by high concentrations what? (3)
- lactate, glycerol and amino acids
L> high fat diet, starvation and prolonged fasting make large quantities of these available
Gluconeogenesis Regulation:
- What are the four key enzymes ?
- pyruvate carboxylase, pep carboxykinase, f-1,6-bisphosphatase , g-6-phosphatase
L> affected by allosteric modulators
Gluconeogenesis Regulation:
1. fructose-1,6-bisphosphatase; activated by? inhibited by?
- activated: ATP, inhibited: AMP and fructose-2,6-bisphosphate
Gluconeogenesis Regulation:
-enzyme Regulation via hormones
L> Glucagon?
- depresses synthesis of f-2,6-bisphosphate which releases inhibition of f-1,6-bisphosphatase and inactivates the glycol tic enzyme pyruvate kinase.
Gluconeogenesis Regulation:
- enzyme regulation via hormones?
L> cortisol ?
- gluconeogenic enzymes are stilted by this….
Gluconeogenesis Regulation:
- enzyme regulation via hormones?
L>Insulin
- leads to the synthesis of new molecules of glucokinase, PFK-1 and PFK-2(glycolysis favoured)
- depresses synthesis of g-6-phosphotase, f-1,6-bisphosphotase and PEP carboxykinase
Gluconeogenesis Regulation:
- Glucagon stimulates what?
synthesis of PEP carboxykinase, f-1,6-bisphosphotase and g-6-phosphatase (gluconeogenesis favoured)
The direction of flux either glycolysis or gluconeogenesis is determined by the ratio of ___to ___.
L> after carb meal?
L> starvation or low fat, low carb meal
insulin to glucagon
L> after carb meal :
Insulin/glucagon ratio is high and glycolysis predominates over gluconeogenesis
L> fasting or low fat low carb meal:
- insulin/glucagon ratio is low and gluconeogenesis predominates over glycolysis.
Gluconeogenesis Regulation:
- ATP?
- high levels of AMP= increase flux through glycolysis at expense of gluconeogenesis
- low levels of AMP= increase in flux through gluconeogenesis at the expense of glycolysis
Gluconeogenesis Regulation:
- control at the PFK-1/Fructose-1,-6-bisphosphatase cycle vs pyruvate kinase for ?
- control at pyruvate kinase is key because it permits the maximal retention of PEP which is very high in phosphate transfer potential
What are the products of the pentose phosphate pathway?
- NOT ATP
- NADPH(powerful antioxidant and needed for for reductive processes), ribose-5-phosphate
Pentose phosphate pathway:
- occurs where?
- how many stages?
- explain the stage(s)
- cytoplasm
- two: oxidative (3 rxn) and non-oxidative
-oxidative: G-6-P—->D-ribulose-5-phosphate
L> producing two NADPH, 1 CO2
-non-oxidative: D-ribulose-5-phosphate ribose-5-phosphate and glyceraldehyde-3-phosphate and fructose-6-phosphate (glyc intermediates are formed when more NADPH is needed vs pentose phosphates.
Pentose phosphate pathway:
- oxidative phase is very active in what? (2)
L> absent in?
RBC’s or hepatocytes that demand high NADPH
L> this phase is virtually absent in cells that synthesize little or no lipid. (muscle cells)
Pentose phosphate pathway:
- G-6-PD catalyzes a key regulatory step in the pentose phosphate pathway and is actively inhibited by _____ and stimulated by___.
- NADPH and GSSG
Several sugars other than glucose are important to vertebrates such as? (3)
- galactose, fructose and mannose
Next to glucose what is the other main carbohydrate source in the human diet?
FRUCTOSE YO
How many places can fructose enter glycolysis?
TWO SPOTS
L> in the liver
L> in muscle and adipose tissue
Explain fructoses conversion in the liver to enter glycolysis!
- fructose ——-fructokinase—-> Fructose-1-phosphate
F-1-P———-> DHAP + Glyceraldehyde
DHAP Glyceraldehyde-3-phosphate
Glyceraldehyde ——–> glyceraldehyde-3-phosphate
(ATP in and ADP out)
**enters at the end of rxn five to undergo six and the rest of glycolysis
Explain fructoses conversion in muscle tissue or adipose tissue to enter glycolysis!
- Fructose ——-> fructose-6-phosphate
ATP in and ADP out) (enter at rxn three
Explain where mannose enters glycolysis!
Mannose—–> mannose-6-phosphate
(ATP in ADP out)
L> isomerizes to Fructose-6-phosphate
(enters at rxn three)
Explain where galactose enters glycolysis!
Galactose -------> galactose-1-phosphate (ATP in and ADP out) Galactose-1-phosphate UDP-galactose ( UDP-glucose in and Glucose-1-phosphate out) UDP-galactose UDP-glucose (substrate for glycogen synthesis) UDP-glucose Glucose-1-phosphate (UTP in and PPi out) Glucose-1-phosphate glucose-6-phosphate ( enters at rxn 2)
The conversion of fructose-1-phopshate into glycolytic intermediates bypasses two regulatory steps (runs catalyzed by ___ and ___) thus in comparison to glucose the entrance of fructose into glycolysis is essentially ____.
hexokinase
PFK-1
unregulated
In muscle and adipose tissue, fructose is converted to the glycolytic intermediate fructose-6-phosphate by hexokinase. Why does this only occur when fructose consumption is exceptionally high?
- the affinity for hexokinase to fructose is very low
Both glycogenesis and glycogenolysis are controlled primarily by three hormones: ___,____ and ____.
insulin, glucagon and epinephrine
When does glycogenesis occur?
- after a meal when blood glucose levels are high!
Whats the first rxn in glycogenesis?
- Glucose-6-phosphate[ Glucose-1,6-bisphosphate ] Glucose-1-phosphate
Whats the second rxn in glycogenesis?
- Glucose-1-phosphate +UDP UDP-glucose + PPi
( driven to completion because PPi +H2O —-> Pi) **immediately occurs and is irreversible with a large loss of free energy delta G prime knot = -33.5Kj/mol
Whats the third rxn in glycogenesis?
- (a) UDP-Glucose + Glycogen primer (n residues) ———glycogen synthase—-> Glycogen (n+1 residues) + UDP ** alpha (1,4) glycosidic bond btwn glucose and the growing glycogen chain***
(b) Glycogen (n+1 residues) —-branching enzyme——> glycogen
* ** branching enzyme creates alpha (1,6) bonds in glycogen
Glycogen synthesis requires a pre-existing what?
tetrasaccharide made up of four alpha (1,4) glycosidic linked glucose residues
L> the first of which is liked to a tyrosine residue n a primer protein called glycogenin
How is the glycogen chain extended in glycogenesis ?
0 via glycogen synthase and branching enzyme
Glycogenolysis?
L> what is it?
L> how many reactions?
- degradation of glycogen
- two reactions
Glycogenolysis
1. What is the first reaction?
- Glycogen —–glycogen phopshorylase—> Glycogen + glucose-1-phosphate
L> this removal of glucose residues is from the nonreducing ends of glycogen and continues until there are only four residues left at the branch point in the glycogen molecule.
- the enzyme involved uses Pi to cleave at alpha (1,4) linkages on the outer branches of glycogen.
Glycogenolysis:
2. Explain the second reaction!
- Hydrolysis of the alpha (1,6) glycosidic bonds at branch points of glycogen. Amylo alpha (1,6) glucosidase = debranching enzyme…begins with the removal of apha (1,6) branch points by transferring the outer three of the four glucose residues attached to the branch point to a nearby nonreducing end. Then it removes the single glucose residue attached at each branch point. Product= free glucose (glucose-1-phosphate)
Regulation of Glycogen Metabolism:
1. Glucagon ?
- released from pancreas when BL Glucose is low in the hours after a meal…binds to receptors on hepatocytes and initiates a signal transduction process that elevates intracellular cAMP levels which amplifies the original glucagon signal initiating a phosphorylation cascade activating glycogen phosphorylase….leading to glycogenolysis…= free glucose.
Regulation of Glycogen Metabolism:
2. Insulin ?
- when the insulin receptor is occupied it becomes an active tyrosine kinase enzyme that causes phosphorylation cascade which has the opposite effect of the glucagon/cAMP system: enzymes of glycogenolysis are inhibited and glycogenesis is activated.
- insulin also increases the rate of glucose uptake in several target cells BUT not the LIVER or brain cells.
Regulation of Glycogen Metabolism:
3. Epinephrine ?
- emotional or physical stress causes the releasal of this
- promotes glycogenolysis and inhibits glycogenesis!
- in emergency situations when massive amounts of it are released…producing of glucose sky rockets to provide energy to manage the situation
Regulation of Glycogen Metabolism:
- Glycogen synthase has two conformations?
- Glycogen phosphorylase has two conformations?
- Active form = I(independent)
Inactive form= D(dependent )
L> I is converted to D via phosphorylation - Inactive form=phosphorylase b
Active form=phosphorylase a
L> inactive ——> active by phosphorylation of a serine residue
Physiologically what are the most important kinases?
- glycogen kinase 3 (GSK3) and casein kinase 1 (CS1)
Regulation of Glycogen Metabolism:
- Glycogen synthase
- Glycogen phosphorylase
- both are converted between conformations by what enzyme? what activates it?
- phosphorylase kinase
L> CAMP
Glycogen synthesis occurs when ___ and ____ have been dephosphorylated. This conversion is catalzyed by phosphoprotein phosphatase 1 (PP1) which also inactivates ___.
glycogen synthase and glycogen phosphorylase
-phosphorylase kinase
What are calcium ions and AMP levels effect on glycogen metabolism?
- when calcium ions and AMP is released during muscle contractions they bind to sites on glycogen phosphorylase b and promote its conversion to phosphorylase a.
The reverse conversion of glycogen phosphorylase a to phosphorylase b is promoted by what?
huh levels of ATP and g-6-p
