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Biochemistry > Chapter8 Carbohydrate Metabolism > Flashcards

Chapter8 Carbohydrate Metabolism Flashcards

1
Q

What is meant by metabolism?

A

Set of reactions that leads to the homeostasis of the cell

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2
Q

When a glucose molecule is completely oxidized how many CO2 molecules is released?

A

6

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3
Q

What is glycogenesis?

A

The conversion of glucose into glycogen

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4
Q

What is glycogenolysis?

A

The conversion of glycogen into glucose

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5
Q

What is glycolysis?

A

The catabolic conversion of glucose (6C) into two pyruvate (3C), in an anaerobic process in a 10 step reaction, producing 2 net ATP & 2 NADH, in the cytoplasm

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6
Q

What is gluconeogenesis?

A

The conversion of pyruvate into glucose

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7
Q

What is meant by the pentose-phosphate pathway?

A

The conversion of glucose into pentose and other sugars

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8
Q

What can happen to the pyruvate?

A

Either goes to citric acid cycle/electron transport system/fatty acids or lactate

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9
Q

What is meant by oxidative phosphorylation?

A

The conversion of NADH into ATP through electron transport chain

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10
Q

How many stages are there in glycolysis & what is the difference between them?

A

1) stage 1 (energy investment)

2) stage 2 (energy producing)

Summarized pathway of glucose:
D-Gluoes + 2 ADP + 2 Pi + 2 NAD(+) = 2 pyruvate + 2 ATP + 2 NADH + 2 H(+) + 2 H2O

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11
Q

How many reactions are there in glycolysis & what are the regulatory steps (reactions that goes in one direction only)?

A

10 reactions, regulatory steps are 1, 3, & 10

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12
Q

What is the first reaction in glycolysis?

A

A regulatory step, converting

Glucose into glucose-6-phosphate, using ATP & hexokinase enzyme (all kinases requires magnesium as a cofactor)

This steps traps the glucose into the cell, & assures that free glucose concentration inside the cell is low to create a higher concentration gradient for its entry

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13
Q

What is the second reaction in glycolysis?

A

Isomerization reaction, converts:

Glucose-6-phosphate into fructose-6-phosphate, using phosphoglucoseisomerase enzyme (conversion of Aldose to ketose)

This reaction makes C1 free for its phosphorylation next making it easier for phosphorylation

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14
Q

What is the third reaction in glycolysis?

A

The most regulatory step, converting:

Fructose-6-phosphate into fructose-1,6-bisphosphate, using ATP & phosphofructokinase1 enzyme (Mg2+)

  • Now the glucose is committed to continue through the glycolysis steps “commitment step”
  • Irreversible step as the glucose lost a lot of its free energy
  • when it is split into two Glyceraldehyde-3-phosphate it prevents any of them from going out of the cell
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15
Q

What is the 4th reaction in glycolysis?

A

Aldol Cleavage between carbon number 3 & 4, of fructose-1,6-bisphosphate into dihydroxyacetone phosphate & Glyceraldehyde-3-phosphate, using aldolase enzyme (Aldose ketose cleavage)

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16
Q

What is the 5th reaction in glycolysis?

A

Isomerization reaction converting:

Dihydroxyacetone phosphate into Glyceraldehyde-3-phosphate, using triosephosphate isomerase enzyme

Occurs because dihydroxyacetone phosphate cannot continue in glycolysis (conversion of ketose to Aldose)

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17
Q

What is the sixth reaction in glycolysis (beginning of stage two “revenue stage”)?

A

Oxidation reduction reaction, where Glyceraldehyde-3-phosphate is converted to Glycerate-1,3-bisphosphate using (phosphate, NAD+) Producing (NADH, & H+) via the enzyme Glyceraldehyde-3-phosphate dehydrogenase (creates a high-energy phosphoanhydride bond)

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18
Q

What is the seventh reaction in glycolysis?

A

Substrate level phosphorylation reaction The conversion of glycerate-1,3-bisphosphate (it is a high energy compound “it will be producing ATP”) into glycerate-3-phosphate via the enzyme phosphoglycerate kinase (the only reversible kinase) converting ADP into ATP

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19
Q

What is the eighth reaction in glycolysis?

A

The conversion of Glycerate-3-phosphate into glycerate-2-phosphate using phosphoglycerate mutase requires Mg2+ “isomerase” enzyme (they add a phosphate at C2 & remove phosphate from C3)

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20
Q

What is the ninth reaction in glycolysis?

A

Dehydration reaction converting glycerate-2-phosphate into phosphoenolpyruvate (high energy molecule) producing H2O, via enolase enzyme (keto-enol tautemerization reaction)

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21
Q

What is the 10th reaction in glycolysis?

A

Converting the high energy molecule (phosphoenolpyruvate) into pyruvate producing ATP from ADP via the enzyme pyruvate kinase

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22
Q

What will happen to the pyruvate molecules?

A

1) Under aerobic conditions:

  • translocated from cytoplasm to mitochondrial matrix converted to acetyl-CoA and then to Kreb’s cycle then to ETC

2) Under anaerobic conditions:

Undergoes fermentation either alcoholic or homolactic

  • GLYCOLYSIS WILL BE THE MAIN SOURCE OF ENERGY

1) In homolactic fermentation (Pyruvate will be converted to lactate via lactate dehydrogenase) to convert NADH to NAD+ to maintaining glycolysis in the muscle cells, red blood cells & certain bacterial cells (lactobacillus)

2) (in the alcoholic fermentation it will be converted to ethanol + CO2 using NADH + H+, PRODUCING NAD+ & CO2) occurs in yeast and certain bacterial species (pyruvate will be converted to acetaldehyde via pyruvate carboxylase, then converted to ethanol via alcohol dehydrogenase producing NAD+ for step 6 in glycolysis)

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23
Q

Which enzymes regulates the rate of the glycolytic pathway in a cell?

A

Allosteric enzymes:

1) Hexokinases I (EVERYWHERE), II (SKELETAL MUSCLE), III (EVERYWHERE) & IIII (liver & pancreatic b-cells “glucose sensor” it only works under high glucose concentration “it has a high Km”) these enzymes are used in reaction 1

  • No activator
  • Glucose-6-phosphate & ATP are inhibitors

2) PFK-1 (reaction 3 “commitment step”)

  • Fructose-2,6-bisphosphate (produced by hormones), AMP (it is an indicator of low energy) are activator
  • Citrate (indicates high energy state “first product of TCA cycle) & ATP are inhibitors

3) Pyruvate kinase (reaction 10)

  • Fructose-1,6-bisphosphate (“feed forward activation” product of reaction 3 activates reaction 10) & AMP are activators
  • Acetyl-CoA & ATP are inhibitors

They are regulated allosterically

24
Q

Which hormones regulates glycolysis?

A

Peptide hormone:

1) glucagon

released by pancreatic α-cells when blood glucose is low activates the phosphatase function of PFK-2, thereby reducing the level of fructose-2,6-bisphosphate in the cell. As a result, PFK-1 activity and glycolytic flux are decrease

2) insulin

a peptide hormone released from pancreatic β-cells when blood glucose levels are high.

Activates the kinase function of PFK-2, which increases the level of fructose-2,6-bisphosphate in the cell, in turn increasing glycolytic flux

In cells containing insulin-sensitive glucose transporters (muscle and adipose tissue but not liver or brain), insulin promotes the translocation of glucose transporters to the cell surface. When insulin binds to its cell-surface receptor, the now active receptor protein triggers numerous intracellular signal cascades that involve phosphorylation and dephosphorylation of target enzymes and transcription factors

25
Q

What is meant by gluconeogenesis?

A

The synthesis of glucose from a non-carbohydrate sources (lactate, glycerol, pyruvate “it is the a-keto acid of alanine”, a-ketoacids (the removal of the amine group from amino acid) “precursors for gluconeogenesis”) in the liver

  • Its reactions are the reverse of glycolysis except for the three irreversible reactions which are carried via:

1) conversion of pyruvate to phosphoenol pyruvate via pyruvate carboxylase & pyruate carboxykinase

2) conversion of fructose-1,6-bisphosphate to fructose-6-phosphate via the enzyme fructose-1,6-bisphosphatase

3) conversion of glucose-6-phosphate to glucose via the enzyme in the kidney and the liver glucose-6-phosphatase

Occurs primarily in the liver and to a lesser extent in the kidneys and intestine

26
Q

What is glucogenicamino acid?

A

Amino acids used for glucose synthesis

27
Q

What is the pathway for gluconeogenesis?

A

Reverse of 7 reaction in glycolysis + the 3 irreversible reactions requiring 4 new enzymes for reactions:

1) reaction 1 is reversed by glucose-6-phosphatase enzyme

2) reaction 3 reversed by fructose-1,6-bisphosphatase (allosteric enzyme activated by citrate, inhibited by AMP & fructose-2,6-bisphosphate)

3) reaction 10 requires two steps for it to be reversed (1) conversion of pyruvate to oxaloacetate (a-keto acid of aspartate) by the enzyme pyruvate carboxylate “utilizing ATP, using CO2 & H2O” within the mitochondria, 2) conversion of oxaloacetate to phosphoenolpyruvate by the enzyme PEP carboxykinase “utilizing GTP”)

This reaction consumes 6 ATP

28
Q

How is gluconeogenesis regulated?

A

1) substrate availability

2) hormones (cortisol, insulin, glucagon)

3) Allostericaly

Stimulated by high concentrations of lactate, glycerol, and amino acids

29
Q

What allosteric substrate regulates pyruvate kinase?

A

Activators:

1) Fructose-1,6-bisphosphate

Inhibitors:

1) ATP
2) Acetyl-CoA
3)cAMP-dependent phosphorylation
4) alanine
5) long chain fatty acids

30
Q

What allosteric substrate regulates pyruvate carboxylase?

A

Activator:

1) Acetyl-CoA

31
Q

What is the Pentose phosphate pathway?

A

Its a shunt, its an alternate glucose metabolic pathway, provides the cell with the required NADPH, it can be used as an entry/exit point for offering sugars (ribose, tetroses, heptoses, etc) where no ATP is produced occurs in the cytoplasm

  • Its products are NADPH & Ribose-5-phosphate
  • It has two phases oxidative & nonoxidative
  • regulated to meet the cell’s moment-by-moment
    requirements for NADPH and ribose-5-phosphate
32
Q

How many phases are there in the pentose phosphate pathway?

A

1) oxidative, irreversible phase, three reactions (produce 2 NADPH (used in anabolic processes) & ribulose-5-phosphate)

Glucose-6-phosphate + 2NADP+ + H2O = Ribulose-5-phosphate + 2 NADPH + 2H+ + CO2

2) non-oxidative, reversible phase (produces important intermediates for nucleotide biosynthesis and glycolysis “ribose-5-phosphate, glyceraldehyde-3-phosphate, fructose-6-phosphate” if the cell requires more NADPH than ribose molecules products of the non-oxidative phase can be shuttled into glycolysis)

3 Ribulose-5-phosphate = 1 ribose-5-phosphate + 2 xylulose-5-phosphate = 2 fructose-6-phosphate + Glyceraldehyde-3-phosphate

33
Q

What are the steps of the PPP?

A

Glucose-6-phosphate from the first reaction in glycolysis where a hexokinase transfer a glucose into a glucose-6-phosphate

First phase (irreversible)

1) glucose-6-phosphate converted to = 6-phospho-d-glucono-lactone “producing NADPH & H+”, (catalyzed by glucose-6-phosphate dehydrogenase, “redox reaction”)

2) 6-phospho-d-glucono-lactone is converted to 6-phospho-d-gluconate (hydration reaction “uses H2O”) using gluconolactonase enzyme

3) 6-phospho-d-gluconate will be converted to 3-keto-6-phospho-d-gluconate (‘as an intermediate”, producing NADPH & H+), USING ENZYME 6-phosphogluconate dehydrogenase, which will then be converted into D-ribulose-5-phoshate using H+, producing CO2 (redox reaction)

Second phase (reversible) (we need three of the ribuloses)

1) 1 of the ribuloses will be converted to d-ribose-5-phosphate (via ribosephosphate isomerase), the other 2 will be converted to d-xylulose-5-phosphate (via ribulose-5-phosphate-3-epimerase)

2) d-ribose-5-phosphate will interact with d-xylulose-5-phosphate via transketolase enzyme transferring two carbons from ribose to xylulose forming D-sedoheptulose-7-phosphate and d-glyceraldehyde-3-phosphate

3) d-sedoheptulose-7-phosphate will then interact with d-Glyceraldehyde-3-phosphate via enzyme trransaldolase forming d-fructose-6-phosphate (it will go to glycolysis) and d-erythrose-4-phosphate

4) the other xyluose-5-phosphate will interact with erythrose-4-phosphate via transketolase enzyme producing Glyceraldehyde-3-phosphate and fructose-6-phosphate which will end up into glycolysis

Transketolases & transaldolases requires (thiamine pyrophosphate as a coenzyme)

34
Q

How to metabolise other important sugars?

A

By converting them into an intermediate of glycolysis

1) galactose

2) mannose

3) fructose

35
Q

How can we utilize galactose in glycolysis?

A

In the liver it is:

1) converted to galactose-1-phosphate (using galactokinase, utilizing ATP)

2) galactose-1-phosphate is activated by adding UDP converted to UDP-galactose (using galactose-1-phosphate uridylyltransferase “its deficiency can cause galactosemia” produsing glucose-1-phosphate as a by product)

3) UDP-Galactose is converted to UDP-Glucose (using UDP-Galactose-4-epimerase)

4) UDP-glucose is converted to glucose-1-phosphate (using UDP-Glucosepyrophosphorylase, catalyzing UTP into PPi)

5) glucose-1-phosphate is converted to glucose-6-phosphate (using phosphoglucomutase)

36
Q

How can we utilize mannose in glycolysis?

A

1) mannose is converted to mannose-6-phosphate (using hexokinase “utilizing ATP”)

2) mannose-6-phosphate is converted to fructose-6-phosphate (using phosphomannoseisomerase)

37
Q

How can we utilize fructose into glycolysis?

A

All body except liver:

1) fructose is converted into fructose-6-phosphate (using hexokinase “utilizing ATP”)

In the LIVER:

1) fructose is converted into fructose-1-phosphate (using fructokinase “utilizing ATP”)

2) fructose-1-phosphate is converted to DHAP (dihydroxyacetone phosphate) & glyceraldehyde (using fructose-1-phosphatealdolase)

3) DHAP is converted into glyceraldehyde-3-phosphate reversibly

Glyceraldehyde-3-phosphate & DHAP are part of glycolysis

  • It is unregulated by normal allosteric regulation
38
Q

What is glycogenesis?

A

It is the synthesis of glycogen from glucose subunits, the storage form of glucose

39
Q

What is the main enzyme that catalyzes glycogen?

A

Glycogensynthase (it adds millions of glucose forming a(1,4) glycosidic linkage)

  • its substrate is UDP-Glucose

Converting glucose-6-phosphate into glucose-1-phosphate (using phosphoglucomustase) then converting glucose-1-phosphate into UDP-Glucose (using UDP-glucosepyrophosphorylase)

  • it cannot work from scratch it needs an oligomer of glucose (5/6 attached glucose)

The protein (glycogenin “dimer”) it forms the oligomer for glycogensynthase to work on found in the core of every glycogen

  • it has a branched a(1,6) which cannot occur by glycogensynthase a hydrolysis reaction

We have a branching enzyme “transferase” (which transfers 4/5 “as glycogen synthase can only work on oligomers” glucoses from the end of the polymer and moves it across the chain forming the a(1,6))

40
Q

What is glycogenolysis?

A

The degradation of glycogen using glycogenphosphorylase which cuts the a(1,4) glycosidic linkage

We have two issues:

1) it cuts the bond a(1,4) it releases glucose-1-phosphate

  • we have a phosphoglucomutase enzyme which converts glcose-1-phosphate into glucose-6-phosphate

2) it cannot work on a(1,6) glycosidic linkage, which is cut by the debranching enzyme, whenever it reaches four glucoses from the branching point it will not cut a(1,4), it has a transferase functionality leaving only one glucose molecule at the branching point, then it cuts and release the glucose linked by the a(1,6) linkage which can then be phosphorylated to go to glycolysis or to the blood stream

41
Q

How is the metabolism of glycogen regulated?

A

1) glycogen synthesis occurs when we have a lot of glucoses (after a meal “releasing insulin”)

2) when glucose level is low, glycogen synthesis is inhibited and activation of glycogen phosphorylase breaking down glycogen (due to the release of glucagon & epinephrine)

42
Q

What is the mechanism in glycogen phosphorylase?

A

1) Glucagon (liver) or epinephrine (muscle) will bind to the receptors on the cell activating adenylate Cyclase converting ATP into cAMP (second messenger)

2) cAMP will activate protein kinase enzyme (which will phosphorylates molecules)

3) protein kinase will go to phosphorylase glycogen synthase (converting it to its inactive form)

4) it activates glycogen phosphorylase by phosphrylating phosphorylase kinase converting it to its active form which will then activat glycogen phosphorylase which will break down glycogen

43
Q

Which kinase enzyme is a reversible enzyme in glycolysis?

A

In reaction 7 phosphoglycerate kinase PGK

44
Q

What are the enzymes for each reaction?

A

1) hexokinase

2) phosphoglucoisomerase

3) phosphofructokinase-1

4) aldolase

5) triose phosphate isomerase

6) Glyceraldehyde-3-phosphate dehydrogenase

7) phosphoglyceratekinase

8) phosphoglycerate mutase

9) enolase

10) pyruvate kinase

FYI all kinase requires Mg2+ as a cofactor

45
Q

Glycolysis occurs under aerobic or anaerobic conditions?

A

Anaerobic

46
Q

What is glucokinase?

A

Glucokinase (GK), found in liver as well as in pancreatic β-cells, intestine, and brain, requires much higher glucose concentrations for optimal activity (about 10 mM).
- not inhibited by glucose-6-phosphate.
- GK is a glucose sensor:
- it is highly sensitive to small changes in blood glucose levels.
- In β-cells, the release of insulin in response to rising blood levels of glucose is initiated by GK.
- In the liver, GK plays a key role in the ability to store glucose as glycogen

47
Q

What are the other ways by which glycolysis is regulated?

A

GLUCOSE-INDUCED GENE EXPRESSION

  • Glucose acts as a signalling molecule in lipogenic (i.e., fat-synthesising) organs such as liver and adipose tissue. When there are high concentrations of glucose, the molecule promotes the transcription of genes involved in de novo lipogenesis (synthesis of new fatty acids and triacylglycerols from carbohydrate molecules).
  • Target genes encode enzymes in glycolysis (e.g., aldolase and PK), the pentose phosphate pathway (e.g., glucose-6-phosphate dehydrogenase and transketolase), and fatty acid synthesis (e.g., fatty acid synthase).
48
Q

What are the important substrate for gluconeogenesis?

A

1) lactate (released from the skeletal muscle by the cori cycle, where after its release from the muscle it is converted to pyruvate and then to glucose)

2) glycerol (from the degradation of fat, where in the liver it is converted to glycerol-3-phosphate by glycerol kinase, then its oxidation using NAD+ forms NADH by glycerol phosphate dehydrogenase)

3) alanine (generated from pyruvate in exercising muscles, it is converted to pyruvate then to glucose in the liver)

49
Q

How is fructose-1,6-bisphosphatase regulated allosterically?

A

It is activated via:

1) ATP
2) citrate

Inhibited via:

1) fructose-2,6-bisphosphate

2) AMP

50
Q

What is the reactions of glycogenesis?

A

Set of three reactions into two phases:

Phase 1 (preparatory):

1) synthesis of glucose-1-phosphate from glucose-6-phosphate via phosphoglucomutase

2) synthesis of UDP-glucose from glucose-1-phosphate by UDP-glucose phosphorylase

Phase 2 (elongation):

3) synthesis of glycogen from UDP-Glucose requiring glycogen synthase (to grow the chain) and the branching enzyme creating a(1,6) linkages for the branches

51
Q

Which hormones regulates the metabolism of glycogen?

A

1) insulin (inhibits glycogenolysis and activates glycogenesis)

2) glucagon (activates glycogenolysis)

3) epinephrine (activates glycogenolysis and inhibits glycogenesis)

4) allosteric effectors

52
Q

What is meant by the flux control?

A

The regulation of the flow of substrate and removal of products

53
Q

What is the net equation for gluconeogenesis?

A

2 pyruvate + 4 ATP + 2 GTP + 2NADH + 2H+ + 6H2O = D-Glucose + 4 ADP + 2 GDP + 2 NAD+ + 6 Pi

54
Q

Fructose-2,6-bisphosphate stimulates and inhibits which cycles?

A

Stimulates glycolysis inhibits gluconeogenesis

55
Q

What is the hexose monophosphate shunt?

A

When neither NADPH nor pentose sugars are required for the biosynthesis reactions, metabolite is in the nonoxidative phase in the Pentose-Phosphate-Pathway are converted into glycolytic intermediates that can then be further degraded to generate energy or converted into precursor molecules for biosynthetic processes

Biochemistry (12 decks)

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