Chapter 8: Carbohydrate Metabolism Flashcards Preview

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Flashcards in Chapter 8: Carbohydrate Metabolism Deck (101)
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1
Q

What is glycolysis??

A
  • process of converting glucose to two molecules of pyruvate capturing a small amount of energy
2
Q

What is glycogenesis?

A

when glycogen ( a storage form) is formed when glucose levels are really high

3
Q

What is glycogenolysis ?

A

when glycogen is degraded forming glucose for when glucose levels are very low.

4
Q

What is gluconeogenesis?

A

when glucose is synthesized from noncarbohydrate precursors by reactions.

5
Q

What is the pentose phosphate pathway?

A

enables cells to convert glucose-6-phosphate a derivative of glucose to ribose-5-phosphate and other types of monosaccharides

6
Q

When glucose molecules are not required for immediate energy production it is stored as what??

A

-glycogen in the liver and muscles

7
Q

Glycolysis is an ____ process??

A

anaerobic process which would have been needed in an oxygen poor environment

8
Q

The small amount of energy captured in glycolysis is temporarily stored where?

A
  • ATP and NADH
9
Q

Anaerobic organisms??

A
  • those that do not use oxygen to generate energy
10
Q

Pyruvate can be converted into waste products such as what? (3)

A

ethanol, lactic acid and acetic acid

11
Q

Aerobic respiration??

A

when oxygen is sued as a terminal electron acceptor….via completely oxidizing pyruvate to form CO2 and H2O in an elaborate stepwise mech.

12
Q

Glycolysis consists of how many reactions and stages?

A
  • 10 reactions

- 2 stages

13
Q

Do a brief overview of what happens in each stage of glycolysis?

A
  1. Glucose —-> Glyceraldehyde-3-phosphate..consuming two ATP
  2. Glyceraldehyde-3-phosphate—-> 2 pyruvates
    L> 4 ATP and 2 NADH
    L> technically the net gain of ATP is actually 2
14
Q

What is the net equation for glycolysis?

A

D-Glucose + 2 ADP + 2Pi + 2NAD+ —–> 2 pyruvate + 2 ATP + 2 NADH + 2H+ + 2H2O

15
Q

What occurs in reaction one for glycolysis?

A

Glucose —> Glucose-6-phosphate

- 1 ATP in and 1 ADP via hexokinase and Mg 2+

16
Q

What occurs in reaction two for glycolysis?

A

Glucose-6-phosphate fructose-6-phosphate

L> via phosphoglucoiosmerase

17
Q

What occurs in reaction three for glycolysis?

A

Fructose-6-phosphate——> Fructose-1,6-bisphosphate
L> via PKF-1 ( phosphofructokinase-1)
L>One ATP in and one ADP out

18
Q

What occurs in reaction four for glycolysis?

A

Fructose-1,6-bisphosphate Dihydroxyacetone phosphate (DHAP) + Glyceraldehyde-3-phosphate
L> via aldolase

19
Q

What occurs in reaction five for glycolysis?

A

—> DHAP Glyceraldehyde-3-phosphate via triose phosphate isomerase

20
Q

What occurs in reaction six for glycolysis?

A

Glyceraldehyde-3-phosphate Glycerate-1,3-bisphosphate
L> via glyceraldehyde-3-phosphate dehydrogenase
L> Pi+ NAD+ in and NADH + H+ out

21
Q

What occurs in reaction seven for glycolysis?

A

Glycerate-1,3-bisphosphate glycerate-3-phosphate
L> via phosphoglycerate kinase
L> one ADP in and one ATP out

22
Q

What occurs in reaction eight for glycolysis?

A

Glycerate-3-phosphate Glycerate-2-phosphate

L> via phosphoglycerate mutase

23
Q

What occurs in reaction nine for glycolysis?

A

Glycerate-2-phosphate phosphoenolpyruvate (PEP)
L> enolase
(H2O out)

24
Q

What occurs in reaction ten for glycolysis?

A

phosphoenolpyruvate ———-> Pyruvate
L>via pyruvate kinase
L> ADP in and ATP out

25
Q

What are the products of glycolysis for one molecule of glucose?

A

2 ATP, 2 NADH, 2 Pyruvate

26
Q

Under aerobic conditions what happens to pyruvate?

A
  • 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
27
Q

The electron transport system??

A

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

28
Q

Under anaerobic conditions what happens to pyruvate?

A
  • 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
29
Q

In yeast what happens to pyruvate?

A
  • decarboxylated to form acetaldehyde which is then reduced by NADH to form ethanol!
30
Q

What three reactions in glycolysis have negative delta G values?

A

1, 3 and 10!
( catalyzed by hexokinase, PFK-1 and pyruvate kinase)
L> all of which are irreversible

31
Q

What are the delta G values for the remaining reactions (2,4-9) in glycolysis?

A
  • 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.
32
Q

During gluconeogenesis which reactions does it bypass?

A
  • 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.

33
Q

Glycolysis is regulated by what? (3)

A
  • 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
34
Q

Glycolysis regulation:

What is hexokinase inhibited by?

A
  • excess g-6-p
35
Q

Glycolysis regulation:

- PFK-1 and pyruvate kinase are activated by what??

A

High AMP levels

indicator for low energy production

36
Q

Glycolysis regulation:

What inhibits both PFK-1 and pyruvate kinase?

A
  • high levels of ATP
37
Q

Glycolysis regulation:

When ATP is in a high concentration citrate and acetyl-CoA accumulate and inhibit what?

A
  • PFK-1 and pyruvate kinase
38
Q

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?

A

PFK-1

39
Q

Glycolysis regulation:

Accumulation of fructose-1,6-bisphosphate activates what?

A

pyruvate kinase

40
Q

Glycolysis is also regulated by what two hormones?

A

Glucagon and insulin

41
Q

Glycogen released by pancreatic cells when blood glucose levels are low activates what?

A

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

42
Q

Glycolysis regulation:

Cyclic AMP?

A
  • a second messenger produced from ATP in a reaction catalyzed by adenylate cyclase….it binds to and activates protein kinase A
43
Q

Glycolysis regulation:

Insulin?

A

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.

44
Q

Glycolysis regulation:

  • Hexokinase activator and inhibitor?
  • PFK-1 activator and inhibitor ?
  • Pyruvate kinase activator and inhibitor?
A
  • 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
45
Q

What are the precursors involved in gluconeogenesis?

A
  • lactate, pyruvate, glycerol and alpha-keto acids
46
Q

The reaction sequence for gluconeogenesis is basically what?

A
  • the reverse of glycolysis….but alternative reactions occur in place of the three irreversible reactions in glycolysis
47
Q

Explain briefly the first reaction that is bypassed from glycolysis in gluconeogenesis?

A
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)
48
Q

How is OAA transported across the mitochondrial membrane ?

A
  • its impermeable to OAA
    L> Malate shuttle
    L> OAA is converted to Malate…..and then reversed to OAA once in the cytoplasm
49
Q

Explain briefly the second reaction that is bypassed from glycolysis in gluconeogenesis?

A

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

50
Q

Explain briefly the third reaction that is bypassed from glycolysis in gluconeogenesis?

A

formation of glucose from g-6-p

51
Q

Substrate cycle??
L> ex?
L> coordinately regulated?

A
  • 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.
52
Q

Flux control??

A

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.

53
Q

Compare glycolysis and gluconeogenesis in terms of ATP!

A
  • glycolysis = energy generating
  • gluconeogenesis = energy consuming
    L> requires the hydrolysis of six high energy phosphate bonds instead of generating ATP
54
Q

Gluconeogenesis substrates :

1. Lactate

A
  • 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
55
Q

Gluconeogenesis substrates :

2.Glycerol

A

-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

56
Q

Gluconeogenesis substrates :

3. Amino acids: Alanine

A
  • 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
57
Q

Gluconeogenesis substrates :

What happens to alanine once its been transported to the liver?

A

its reconverted into pyruvate and then glucose

58
Q

Gluconeogenesis substrates :
3. cont..
Glucose-alanine cycle

A
  • 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.
59
Q

Gluconeogenesis Regulation:

- what three ways is it primarily regulated?

A
  • substrate availability, allosteric effectors and hormones
60
Q

Gluconeogenesis Regulation:

- It is stimulated by high concentrations what? (3)

A
  • lactate, glycerol and amino acids

L> high fat diet, starvation and prolonged fasting make large quantities of these available

61
Q

Gluconeogenesis Regulation:

- What are the four key enzymes ?

A
  • pyruvate carboxylase, pep carboxykinase, f-1,6-bisphosphatase , g-6-phosphatase
    L> affected by allosteric modulators
62
Q

Gluconeogenesis Regulation:

1. fructose-1,6-bisphosphatase; activated by? inhibited by?

A
  • activated: ATP, inhibited: AMP and fructose-2,6-bisphosphate
63
Q

Gluconeogenesis Regulation:
-enzyme Regulation via hormones
L> Glucagon?

A
  • depresses synthesis of f-2,6-bisphosphate which releases inhibition of f-1,6-bisphosphatase and inactivates the glycol tic enzyme pyruvate kinase.
64
Q

Gluconeogenesis Regulation:
- enzyme regulation via hormones?
L> cortisol ?

A
  • gluconeogenic enzymes are stilted by this….
65
Q

Gluconeogenesis Regulation:
- enzyme regulation via hormones?
L>Insulin

A
  • 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
66
Q

Gluconeogenesis Regulation:

- Glucagon stimulates what?

A

synthesis of PEP carboxykinase, f-1,6-bisphosphotase and g-6-phosphatase (gluconeogenesis favoured)

67
Q

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

A

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.

68
Q

Gluconeogenesis Regulation:

- ATP?

A
  • 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
69
Q

Gluconeogenesis Regulation:

- control at the PFK-1/Fructose-1,-6-bisphosphatase cycle vs pyruvate kinase for ?

A
  • control at pyruvate kinase is key because it permits the maximal retention of PEP which is very high in phosphate transfer potential
70
Q

What are the products of the pentose phosphate pathway?

A
  • NOT ATP

- NADPH(powerful antioxidant and needed for for reductive processes), ribose-5-phosphate

71
Q

Pentose phosphate pathway:

  • occurs where?
  • how many stages?
  • explain the stage(s)
A
  • 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.
72
Q

Pentose phosphate pathway:
- oxidative phase is very active in what? (2)
L> absent in?

A

RBC’s or hepatocytes that demand high NADPH

L> this phase is virtually absent in cells that synthesize little or no lipid. (muscle cells)

73
Q

Pentose phosphate pathway:
- G-6-PD catalyzes a key regulatory step in the pentose phosphate pathway and is actively inhibited by _____ and stimulated by___.

A
  • NADPH and GSSG
74
Q

Several sugars other than glucose are important to vertebrates such as? (3)

A
  • galactose, fructose and mannose
75
Q

Next to glucose what is the other main carbohydrate source in the human diet?

A

FRUCTOSE YO

76
Q

How many places can fructose enter glycolysis?

A

TWO SPOTS
L> in the liver
L> in muscle and adipose tissue

77
Q

Explain fructoses conversion in the liver to enter glycolysis!

A
  • 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

78
Q

Explain fructoses conversion in muscle tissue or adipose tissue to enter glycolysis!

A
  • Fructose ——-> fructose-6-phosphate

ATP in and ADP out) (enter at rxn three

79
Q

Explain where mannose enters glycolysis!

A

Mannose—–> mannose-6-phosphate
(ATP in ADP out)
L> isomerizes to Fructose-6-phosphate
(enters at rxn three)

80
Q

Explain where galactose enters glycolysis!

A
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)
81
Q

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 ____.

A

hexokinase
PFK-1
unregulated

82
Q

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?

A
  • the affinity for hexokinase to fructose is very low
83
Q

Both glycogenesis and glycogenolysis are controlled primarily by three hormones: ___,____ and ____.

A

insulin, glucagon and epinephrine

84
Q

When does glycogenesis occur?

A
  • after a meal when blood glucose levels are high!
85
Q

Whats the first rxn in glycogenesis?

A
  1. Glucose-6-phosphate[ Glucose-1,6-bisphosphate ] Glucose-1-phosphate
86
Q

Whats the second rxn in glycogenesis?

A
  1. 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

87
Q

Whats the third rxn in glycogenesis?

A
  1. (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
88
Q

Glycogen synthesis requires a pre-existing what?

A

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

89
Q

How is the glycogen chain extended in glycogenesis ?

A

0 via glycogen synthase and branching enzyme

90
Q

Glycogenolysis?
L> what is it?
L> how many reactions?

A
  • degradation of glycogen

- two reactions

91
Q

Glycogenolysis

1. What is the first reaction?

A
  1. 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.
92
Q

Glycogenolysis:

2. Explain the second reaction!

A
  1. 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)
93
Q

Regulation of Glycogen Metabolism:

1. Glucagon ?

A
  1. 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.
94
Q

Regulation of Glycogen Metabolism:

2. Insulin ?

A
  1. 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.
95
Q

Regulation of Glycogen Metabolism:

3. Epinephrine ?

A
  • 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
96
Q

Regulation of Glycogen Metabolism:

  1. Glycogen synthase has two conformations?
  2. Glycogen phosphorylase has two conformations?
A
  1. Active form = I(independent)
    Inactive form= D(dependent )
    L> I is converted to D via phosphorylation
  2. Inactive form=phosphorylase b
    Active form=phosphorylase a
    L> inactive ——> active by phosphorylation of a serine residue
97
Q

Physiologically what are the most important kinases?

A
  • glycogen kinase 3 (GSK3) and casein kinase 1 (CS1)
98
Q

Regulation of Glycogen Metabolism:

  1. Glycogen synthase
  2. Glycogen phosphorylase
    - both are converted between conformations by what enzyme? what activates it?
A
  • phosphorylase kinase

L> CAMP

99
Q

Glycogen synthesis occurs when ___ and ____ have been dephosphorylated. This conversion is catalzyed by phosphoprotein phosphatase 1 (PP1) which also inactivates ___.

A

glycogen synthase and glycogen phosphorylase

-phosphorylase kinase

100
Q

What are calcium ions and AMP levels effect on glycogen metabolism?

A
  • 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.
101
Q

The reverse conversion of glycogen phosphorylase a to phosphorylase b is promoted by what?

A

huh levels of ATP and g-6-p