Download Principles of BIOCHEMISTRY

yes no Was this document useful for you?
   Thank you for your participation!

* Your assessment is very important for improving the work of artificial intelligence, which forms the content of this project

Document related concepts

Biochemistry wikipedia, lookup

Fatty acid metabolism wikipedia, lookup

Amino acid synthesis wikipedia, lookup

Fatty acid synthesis wikipedia, lookup

Metalloprotein wikipedia, lookup

Glucose wikipedia, lookup

Glycolysis wikipedia, lookup

Metabolism wikipedia, lookup

Biosynthesis wikipedia, lookup

Evolution of metal ions in biological systems wikipedia, lookup

Digestion wikipedia, lookup

Microbial metabolism wikipedia, lookup

Photosynthesis wikipedia, lookup

Citric acid cycle wikipedia, lookup

Enzyme wikipedia, lookup

Ketosis wikipedia, lookup

Glyceroneogenesis wikipedia, lookup

Lipid signaling wikipedia, lookup

Oxidative phosphorylation wikipedia, lookup

Enzyme inhibitor wikipedia, lookup

Photosynthetic reaction centre wikipedia, lookup

Nicotinamide adenine dinucleotide wikipedia, lookup

Adenosine triphosphate wikipedia, lookup

Lactate dehydrogenase wikipedia, lookup

Biochemical cascade wikipedia, lookup

NADH:ubiquinone oxidoreductase (H+-translocating) wikipedia, lookup

Electron transport chain wikipedia, lookup

Phosphorylation wikipedia, lookup

Blood sugar level wikipedia, lookup

Lac operon wikipedia, lookup

• Overview of
• Catabolism of glucose via
glycolysis and the citric
acid cycle
Net reaction of glycolysis
Converts: 1 glucose
2 pyruvate
• Two molecules of ATP are produced
• Two molecules of NAD+ are reduced to NADH
Glucose + 2 ADP + 2 NAD+ + 2 Pi
2 Pyruvate + 2 ATP + 2 NADH + 2 H+ + 2 H2O
Glycolysis can be divided into two stages
• Hexose stage: 2 ATP are consumed per glucose
• Triose stage: 4 ATP are produced per glucose
Net: 2 ATP produced per glucose
Fig 11.2
Transfer of a phosphoryl
group from ATP to glucose
enzyme: hexokinase
Isomerization of
glucose 6-phosphate
to fructose 6-phosphate
enzyme: glucose 6-phosphate isomerase
Transfer of a second
phosphoryl group from
ATP to fructose 6-phosphate
enzyme: phosphofructokinase-1
Carbon 3 – Carbon 4
bond cleavage,
yielding two
triose phosphates
enzyme: aldolase
Enzyme 1. Hexokinase
• Transfers the g-phosphoryl of ATP to glucose C-6 oxygen to
generate glucose 6-phosphate
• Mechanism: attack of C-6 hydroxyl oxygen of glucose on the
g-phosphorous of MgATP2- displacing MgADP-
Fig 11.3
2. Glucose 6-Phosphate Isomerase
• Converts glucose 6-phosphate (an aldose) to
fructose 6-phosphate (a ketose)
• Enzyme converts glucose 6-phosphate to open
chain form in the active site
Fig 11.4
3. Phosphofructokinase-1 (PFK-1)
• Catalyzes transfer of a phosphoryl group from ATP
to the C-1 hydroxyl group of fructose 6-phosphate
to form fructose 1,6-bisphosphate (F1,6BP)
• PFK-1 is metabolically irreversible and a critical
regulatory point for glycolysis in most cells
(PFK-1 is the first committed step of glycolysis)
4. Aldolase
• Aldolase cleaves the hexose fructose 1,6-bisphosphate
into two triose phosphates: glyceraldehyde 3phosphate and dihydroxyacetone phosphate
5. Triose Phosphate Isomerase
• Conversion of dihydroxyacetone phosphate
into glyceraldehyde 3-phosphate
Fig 11.6 Fate of carbon atoms from
hexose stage to triose stage
6. Glyceraldehyde 3-Phosphate
Dehydrogenase (GAPDH)
• Conversion of glyceraldehyde 3-phosphate to
1,3-bisphosphoglycerate (1,3BPG)
• Molecule of NAD+ is reduced to NADH
Box 11.2 Arsenate (AsO43-) poisoning
• Arsenate can replace Pi as a substrate for
glyceraldehyde 3-phosphate dehydrogenase
• Arseno analog which forms is unstable
7. Phosphoglycerate Kinase
• Uses uses the high-energy phosphate of
1,3-bisphosphoglycerate to form ATP from ADP
• Transfer of phosphoryl group from the energy-rich
1,3-bisphosphoglycerate to ADP yields ATP and
8. Phosphoglycerate Mutase
• Catalyzes transfer of a phosphoryl group from one
part of a substrate molecule to another
• Reaction occurs without input of ATP energy
9. Enolase: 2-phosphoglycerate to
phosphoenolpyruvate (PEP)
• Elimination of water (dehydration) yields PEP
• PEP has a very high phosphoryl group transfer
potential because it exists in its unstable enol form
10. Pyruvate Kinase
• Metabolically irreversible
Fates of pyruvate
• For centuries, bakeries
and breweries have
exploited the
conversion of glucose
to ethanol and CO2 by
glycolysis in yeast
Metabolism of Pyruvate
1. Aerobic conditions: pyruvate is oxidized to
acetyl CoA, which enters the citric acid cycle
for further oxidation
2. Anaerobic conditions (microorganisms):
pyruvate is converted to ethanol
3. Anaerobic conditions (muscles, red blood
cells): pyruvate is converted to lactate
Fig 11.10
• Fates of pyruvate
Fig 11.11
• Two enzymes required:
(1) Pyruvate decarboxylase
(2) Alcohol dehydrogenase
• Anaerobic
conversion of
pyruvate to ethanol
(yeast - anaerobic)
Reduction of Pyruvate to Lactate
(muscles - anaerobic)
• Muscles lack pyruvate dehydrogenase and cannot produce
ethanol from pyruvate
• Muscle lactate dehydrogenase converts pyruvate to lactate
• This reaction regenerates NAD+ for use by glyceraldehyde 3phosphate dehydrogenase in glycolysis
• Lactate formed in skeletal muscles during exercise is
transported to the liver
• Liver lactate dehydrogenase can reconvert lactate to pyruvate
• Lactic acidosis can result from insufficient oxygen (an increase
in lactic acid and decrease in blood pH)
Reduction of pyruvate to lactate
Glucose + 2 Pi2- + 2 ADP3-
2 Lactate- + 2 ATP4- + 2 H2O
Metabolically Irreversible Steps of Glycolysis
• Enzymes not reversible:
Reaction 1 - hexokinase
Reaction 3 - phosphofructokinase
Reaction 10 - pyruvate kinase
• These steps are metabolically irreversible, and
these enzymes are regulated
• All other steps of glycolysis are near equilibrium in
cells and not regulated
Regulation of Glycolysis
1. When ATP is needed, glycolysis is activated
• Inhibition of phosphofructokinase-1 is relieved.
• Pyruvate kinase is activated.
2. When ATP levels are sufficient, glycolysis activity
• Phosphofructokinase-1 is inhibited.
• Hexokinase is inhibited.
Fig 11.13
Glucose transport
into the cell
Fig 11.14 Regulation of glucose transport
• Glucose uptake into skeletal and heart muscle and
adipocytes by GLUT 4 is stimulated by insulin
Regulation of Hexokinase
• Hexokinase reaction is metabolically irreversible
• Glucose 6-phosphate (product) levels increase
when glycolysis is inhibited at sites further along
in the pathway
• Glucose 6-phosphate inhibits hexokinase.
Regulation of Phosphofructokinase-1 (PFK-1)
• ATP is a substrate and an allosteric inhibitor of PFK-1
• High concentrations of ADP and AMP allosterically
activate PFK-1 by relieving the ATP inhibition.
• Elevated levels of citrate (indicate ample substrates for
citric acid cycle) also inhibit Phospofructokinase-1
Regulation of PFK-1 by Fructose 2,6bisphosphate (F2,6BP)
• Fructose 2,6-bisphosphate is formed from
Fructose 6-phosphate by the enzyme
phosphofructokinase-2 (PFK-2)
• Fig 11.17 Fructose 2,6-bisphosphate
Formation and hydrolysis of
Fructose 2,6-bisphosphate
Prentice Hall c2002
Chapter 11
Fig. 11.18
• Effect of
on liver
Prentice Hall c2002
Chapter 11
Regulation of Pyruvate Kinase (PK)
• Pyruvate Kinase is
allosterically activated
by Fructose 1,6bisphosphate, and
inhibited by ATP
• The hormone
glucagon stimulates
protein kinase A,
which phosphorylates
Pyruvate Kinase,
converting it to a less
active form.
Prentice Hall c2002
Chapter 11
Other Sugars Can Enter Glycolysis
• Glucose is the main metabolic fuel in most organisms
• Other sugars convert to glycolytic intermediates
• Fructose and sucrose (contains fructose) are major
sweeteners in many foods and beverages
• Galactose from milk lactose (a disaccharide)
• Mannose from dietary polysaccharides, glycoproteins
Prentice Hall c2002
Chapter 11
Fructose Is Converted to
Glyceraldehyde 3-Phosphate
Galactose is Converted to
Glucose 1-Phosphate
Fig 11.22
Mannose is Converted to
Fructose 6-Phosphate
Formation of 2,3-Bisphosphoglycerate
in Red Blood Cells
• 2,3-Bisphosphoglycerate (2,3BPG) allosterically
regulates hemoglobin oxygenation (red blood cells)
• Erythrocytes contain bisphosphoglycerate mutase
which forms 2,3BPG from 1,3BPG
• In red blood cells about 20% of the glycolytic flux is
diverted for the production of the important oxygen
regulator 2,3BPG
Prentice Hall c2002
Chapter 11
Fig 11.24
• Formation
of 2,3BPG
in red blood
Feedback inhibition
• Product of a pathway controls the rate of its own synthesis
by inhibiting an enzyme catalyzing an early step
Feed-forward activation
• Metabolite early in the pathway activates
an enzyme further down the pathway
Prentice Hall c2002
Chapter 11