Download Metabolism

Energy Uses and Relationships
Uses of Energy
Biosynthesis
Movement
Active Transport
Metabolism
Metabolism involves
• Catabolic reactions that break
down large, complex molecules
to provide energy and smaller
molecules.
• Anabolic reactions that use
ATP energy to build larger
molecules.
Catabolism: Energy producing, oxidative, convergent
Anabolism: Energy requiring, reductive, divergent
Stages of Metabolism (Catabolism)
Catabolic reactions are organized as
Stage 1:
Digestion and hydrolysis break down large
molecules to smaller ones that enter the bloodstream.
Stage 2:
Degradation breaks down molecules to twoand three-carbon compounds.
Stage 3:
Oxidation of small molecules in the citric
acid cycle and electron transport provide ATP energy.
Stages of Metabolism (Catabolism)
Stages of Metabolism (Anabolism)
Anabolic reactions are organized as
Stage 2:
Energy (ATP) and Reduction used to
convert small molecules into building blocks of larger
molecules.
Stage 1:
Formation of macromolecules
(proteins, polysaccharides, triacylglycerols,
nucleic acids) from their building blocks.
Summary
of
Metabolic
Pathways
Cell Structure
Metabolic reactions occur in specific sites
within cells.
Carbohydrate breakdown
and synthesis, fat synthesis
DNA and RNA synthesis
Recycling
center
Protein
synthesis
Fatty acid oxidation, citric
acid cycle, electron transport
system
Mitochondrion
Key Processes Occurring
Inside the Mitochondrion
Citric Acid (Kreb’s) Cycle
Electron Transport System
Fatty Acid Oxidation
ATP and Energy
Hydrolysis of ATP to ADP and
ADP to AMP
pyrophosphate bonds
Other Energy-rich Phosphates
phosphenolpyruvate+ H2O
pyruvate + Pi + 14.8 kcal
1,3-bisphosphoglycerate + H2O
phosphocreatine + H2O
3-phosphoglycerate + Pi + 11.8 kcal
creatine + Pi + 10.3 kcal
glucose 6-phosphate + H2O
glucose + Pi + 3.3 kcal
glycerol 1-phosphate + H2O
glycerol + Pi + 2.2 kcal
Central Energy Transfer Position of ATP
Structure of Coenzyme NAD+
NAD+
• Is nicotinamide
adenine dinucleotide.
• Contains ADP, ribose,
and nicotinamide.
• Reduces to NADH
when the nicotinamide
group accepts H+ and
2e-.
NAD+ + H+ + 2 e–
NADH
Structure of Coenzyme FAD
FAD
• Is flavin
adenine
dinucleotide.
• Contains ADP
and riboflavin
(vitamin B2).
Key Reaction of Coenzyme FAD
FAD (flavin adenine dinucleotide)
• Participates in reactions that produce a carboncarbon double bond (C=C).
• Is reduced to FADH2.
Oxidation
—CH2—CH2—
—CH=CH— + 2H+ + 2e-
Reduction
FAD + 2H+ + 2e-
FADH2
Structure of Coenzyme A
Carrier of acyl groups, for example acetyl group
O
||
CH3—C— + HS—CoA
acetyl group
O
||
CH3—C—S—CoA
acetyl CoA
Digestion Overview
Mouth: Starch breakdown - catalyzed by a-amylase in saliva
Stomach: Hormone gastrin stimulates gastric gland secretion
HCl and pepsinogen released
Pepsinogen converted to pepsin (protease)
Pepsin catalyzed hydrolysis of protein
Small intestines: Hormone secretion stimulated
Enterogastrone-feeds back to inhibit gastric juice secretion
Secretin-stimulates release of pancreatic juice
containing bicarbonate (neutralizes acid)
Pancreozymin/cholecystokininstimulates pancreas to release digestive enzymes
(proteases, pancreatic lipase, pancreatic amylase)
stimulates gall bladder to release bile
(contains bile salts: emulsifying agents)
Intestinal juice also contains variety of digestive enzymes
(maltase, sucrase, lactase, peptidases, nucleases)
Summary of Carbohydrate
MetabolicPathways
Glycolysis: breaking down glucose
Gluconeogenesis: synthesis of new glucose
Glycogenesis: synthesis of glycogen
Glycogenolysis: breakdown of glycogen
Carbohydrate Catabolism
Stage 2: Glycolysis
• Is a metabolic pathway that uses
glucose, a digestion product.
• Degrades six-carbon glucose
molecules to three-carbon.
pyruvate molecules.
• Also pathway for breakdown
of other monosaccharides
(fructose, galactose, ribose)
Glycolysis:Overview
Consists of two phases
Energy-investing phase Reactions 1 - 5:
glyceraldehyde 3-phosphate +
glucose + 2 ATP
dihydroxyacetone phosphate + 2 ADP
Energy-generating phase: Reactions 6 - 10
2 glyceraldehyde 3 phosphate +4 ADP + 2 Pi + 2 NAD+
2 pyruvate + 4 ATP + 2 NADH + 4 H+ + 2 H2O
Glycolysis:Reactions 1-5
Energy-Investment Phase
4
1
3
2
5
Glycolysis: Reactions 6-10
Energy-producing Phase
9
6
8
7
10
Glycolysis: Overall Reaction
In glycolysis,
• Two ATP add phosphate to glucose and fructose-6-phosphate.
• There is a net gain of 2 ATP and 2 NADH.
• Four ATP are formed in energy-generation by direct transfers of
phosphate groups to four ADP.
C6H12O6 + 2ADP + 2Pi + 2NAD+
glucose
2C3H3O3- + 2ATP + 2NADH + 4H+ + 2 H2O
pyruvate
Pathways for Pyruvate
Pyruvate: Aerobic Conditions
Under aerobic conditions (oxygen present),
• Three-carbon pyruvate is decarboxylated producing
CO2 and an aldehyde group.
• The aldehyde group is oxidized to an acetyl group.
• The acetyl group is transferred to coenzyme A
O O
pyruvate
dehydrogenase
CH3—C—C—O- + HS—CoA + NAD+
pyruvate
O
CH3—C—S—CoA + CO2 + NADH + H+
acetyl CoA
Glycolysis: Anaerobic Conditions
Fermentation
Fermentation
• Occurs in anaerobic microorganisms such as yeast.
• Decarboxylates pyruvate to acetaldehyde, which is then
reduced to ethanol.
• Regenerates NAD+ to continue glycolysis.
O O
CH3—C—C—O- + NADH + H+
pyruvate
OH
CH3—CH2 + NAD+ + CO2
ethanol
Pyruvate: Anaerobic Conditions
Under anaerobic conditions (without oxygen),
• Pyruvate is reduced to lactate.
• NADH oxidizes to NAD+ allowing glycolysis to continue.
O O
lactate
dehydrogenase
CH3—C—C—O- + NADH + H+
pyruvate
OH O
CH3—CH—C—O- + NAD+
lactate
Lactate in Muscles
During strenuous exercise,
• Oxygen in the muscles is depleted.
• Anaerobic conditions are produced.
OH O
• Lactate accumulates.
C6H12O6 + 2ADP + 2Pi
glucose
CH3—CH—C—O- + 2ATP
lactate
• Muscles tire and become painful.
• After exercise, a person breathes heavily to repay
the oxygen debt and reform pyruvate in the liver.
Cori Cycle
The Cori cycle
• Is the flow of lactate and glucose
between the muscles and the liver.
• Occurs when anaerobic conditions
occur in active muscle and
glycolysis produces lactate.
• Operates when lactate moves
through the blood stream to the
liver, where it is oxidized back to
pyruvate.
• Converts pyruvate to glucose, which
is carried back to the muscles.
Cellular Regulation of Glycolysis
Glycolysis is regulated by three enzymes,
• Reaction 1 Hexokinase is inhibited by high
levels of glucose-6-phosphate, which prevents
the phosphorylation of glucose.
• Reaction 3 Phosphofructokinase, an allosteric
enzyme, is inhibited by high levels of ATP and
activated by high levels of ADP and AMP.
• Reaction 10 Pyruvate kinase, another allosteric
enzyme is inhibited by high levels of ATP or
acetyl CoA, activated by fructose 1,6bisphosphate.
Glycolysis (Animated Version)
electron
transport
system
acetyl-CoA
NADH + H+
CoA
blood
glucose
CO2
NAD+
irreversible
(control pt)
aerobic
cellular
ATP glucose
blood
irreversible
(control pt)
phosphoenolpyruvate (2)
pyruvate (2)
hexokinase
lactate
ADP
mitochondrion
ATP (2)
anaerobic
NAD+
glucose
6-phosphate
ADP (2)
pyruvate
kinase
NADH
+ H+
H2O (2)
2-phosphoglycerate (2)
cytoplasm
3-phosphoglycerate (2)
fructose
6-phosphate
ATP
ADP
irreversible
(control pt)
fructose
1,6-bisphosphate
ATP (2)
phosphofructokinase
glyceraldehyde
3-phosphate
dihydroxyacetone
phosphate
NAD+
Pi
NADH + H+
ADP (2)
1,3-bisphosphoglycerate (2)
Gluconeogenesis: Glucose Synthesis
Gluconeogenesis is
• The synthesis of glucose from carbon
atoms of noncarbohydrate compounds.
• Required when glycogen stores are
depleted.
Gluconeogenesis: Glucose Synthesis
Glucose is synthesized from
noncarbohydrates such as lactate,
some amino acids, and glycerol
after they are converted to
pyruvate or other intermediates.
Seven reactions are the reverse
of glycolysis and use the same
enzymes.
Three reactions are not reversible.
Reaction 1 Catalyzed by hexokinase
glucose + ATP
glucose 6-phosphate + ADP
Reaction 3 Catalyzed by phosphofructokinase
fructose 6-phosphate + ATP
fructose 1,6-bisphosphate + ADP
Reaction 10 Catalyzed by pyruvate kinase
phosphoenolpyruvate + ADP
pyruvate+ ATP
Gluconeogenesis: Pyruvate to
Phosphoenolpyruvate
Conversion of pyruvate to phosphoenolpyruvate uses two
reactions that replace the reverse of reaction 10 of glycolysis.
Reaction 1: Pyruvate adds a carbon to form oxaloacetate.
(Carboxylation: Uses 1 ATP)
Reaction 2: A carbon is removed and a phosphate added to
form phosphoenolpyruvate. (Uses 1 GTP)
Total energy cost = 1 ATP + 1 GTP = 2 ATP
Phosphoenolpyruvate to
Fructose-1,6-bisphosphate
• Phosphoenolpyruvate is converted to fructose-1,6bisphosphate using the same enzymes in glycolysis.
• Uses 2 ATP and 2 NADH.
Glucose Formation
Glucose forms when
• A loss of a phosphate from fructose-1,6-bisphosphate
forms fructose-6-phosphate and Pi.
• A reversible reaction converts fructose-6-phosphate to
glucose-6-phosphate.
• A phosphate is removed from glucose-6-phosphate.
• No ATP is produced.
Gluconeogenesis: Overall Reaction
In gluconeogenesis,
• 2 ATP and 2 GTP are used to convert pyruvate to
phosphoenolpyruvate.
• 2 ATP are used to convert 3-phosphoglycerate to 1,3bisphosphoglycerate.
• 2 NADH are used to convert 1,3-bisphosphoglycerate
to glyceraldehyde 3-phosphate.
• There is a net use of 4 ATP, 2GTP, and 2 NADH.
2C3H3O3- + 4ATP + 2 GTP + 2Pi + 2NADH
pyruvate
C6H12O6 + 4ADP + 2 GDP + 2NAD+
glucose
Regulation of Glycolysis and
Gluconeogenesis
TABLE 22.2
Glycogenesis
Glycogenesis
• Stores glucose by converting glucose to glycogen.
• Takes place in liver and skeletal muscle.
• Operates when high levels of glucose-6-phosphate
are formed in the first reaction of glycolysis.
• Does not operate when energy stores (glycogen) are
full, which means that additional glucose is
converted to body fat.
Formation of Glucose-6-Phosphate
In glycogenesis
• Glucose is initially converted to glucose 6-phosphate
using ATP.
O
-
O
P
O CH2
O-
O
OH
OH
OH
glucose-6-phosphate
hexokinase
OH
Formation of Glucose-1-Phosphate
Glucose-6-phosphate is converted to
glucose-1-phosphate.
O
H O CH2
-
O P O CH2
O-
O
O
OH
OH
OH
glucose 6-phosphate
O
OH
OH
O P O-
OH
OH
O-
glucose 1-phosphate
Formation of UDP-Glucose
UTP activates glucose-1phosphate to form UDPglucose and pyrophosphate
(PPi).
O
CH2OH
H
O
OH
O
OH
O
O
O P O P O CH2
OH
-
O
-
O
UDP-glucose
OH
N
N
O
OH
Glycogenesis: Glycogen
The glucose in UDP-glucose adds to glycogen (glucose)n.
UDP-glucose + (glucose)n
(glucose)n+1 + UDP
The UDP reacts with ATP to regenerate UTP.
UDP + ATP
UTP + ADP
glycogen synthase
Diagram of Glycogenesis
glycogen
synthase
hexokinase
Glycogenolysis
In glycogenolysis
• Glycogen is broken down
to glucose.
• Glucose molecules are
removed one by one from
the nonreducing end of
the glycogen chain to
yield glucose-1phosphate.
glucose
6-phosphatase
glycogen
phosphorylase
Glycogenolysis (First Reaction)
glycogen-glucose + Pi
glycogen
phosphorylase
glycogen + glucose-1-phosphate
• Glycogen phosphorylase catalyzes removal and
phosphorylation of glucose from non-reducing
end, producing glucose 1-phosphate.
• Glycogen phosphorylase activated by
glucagon (liver) (low blood glucose)
AMP (skeletal muscle)(energy need)
Epinephrine (emergency energy signal)
Liver: increase blood glucose
Skeletal muscle: provide fuel for glycolysis
Glycogen phosphorylase inhibited by insulin
(liver and skeletal muscle)
glycogen phosphorylase
Hormonal Control
Activated by glucagon (liver)
and epinephrine (liver and muscle)
Inhibited by insulin (liver and muscle)
Glycogenolysis: Second Reaction
Isomerization of Glucose-1-phosphate
• The glucose-1-phosphate isomerizes to glucose-6phosphate, which enters glycolysis for energy
production (primarily in skeletal muscle).
Hydrolysis of Glucose 6-phosphate
Glucose 6-phosphate
• Is not converted by skeletal muscle to glucose
because muscle lacks glucose 6-phosphatase.
• Hydrolyzes to glucose in the liver and kidney, where
glucose 6-phosphatase is available providing free
glucose for the brain and skeletal muscle.
glucose
6-phosphatase
Summary of Glucose Pathways
Blood
glucose
Cell
insulin (+)
insulin (+)
glucagon (–)
glucagon (–)
glucose
ATP
glucagon (+)
insulin (–)
glycogenesis
glycogenolysis
ADP
glucose 6-P
glucagon (+)
insulin (–)
gluconeogenesis
glycolysis
glucagon (+)
glycogen
NAD+
insulin (+)
glucagon (–)
insulin (–)
NAD+
NADH
pyruvate
lactate
anaerobic