Metabolism
Do We Have Enough Energy?
• Nutrients and regulation of appetite
• Carbohydrate metabolism
• Lipid and protein metabolism
• Metabolic states
Nutritious and Delicious
• Nutrient
– An ingested chemical that is used for growth, repair, and
maintenance of the body
– Two categories
• Macronutrients
– Must consume in large quantities
– Water, carbohydrates, lipids , and proteins
• Micronutrients
– Small quantities needed
– Minerals and vitamins
• Calories
– Kcal
– Measure of the capacity to do work
Regulation of Appetite
• Short-term regulators
– Ghrelin – produces sensation of hunger
– Peptide YY (PYY) – sensation of satisfaction
– CCK – sensory stimulus of vagus nerve (suppressor)
• Long-term regulators (adiposity signals)
– Leptin
– Insulin
• Arcuate nucleus of hypothalamus
– NPY - stimulator
– Melanocortin - suppressor
Carbohydrate Metabolism
• dietary carbohydrate burned as fuel within
hours of absorption
• all oxidative carbohydrate consumption is
essentially a matter of glucose catabolism
C6H12O6 + 6O2  6CO2 + 6H2O
• function of this reaction is to transfers energy
from glucose to ATP
– not to produce carbon dioxide and water
Glucose Catabolism
• Glucose catabolism – a series of small steps, controlled by
separate enzymes, in which energy is released in small
manageable amounts, as much possible transferred to ATP and
the rest is released as heat
• Three major pathways of glucose catabolism
– Glycolysis
• glucose (6C) split into 2 pyruvic acid molecules (3C)
– Anaerobic fermentation
• occurs in the absence of oxygen
• reduces pyruvic acid to lactic acid
– Aerobic respiration
• occurs in the presence of oxygen
• completely oxidizes pyruvic acid to CO2 and H2O
Coenzymes
• Enzymes remove electrons (as hydrogen atoms) from
intermediate compounds of these pathways and transfer to
coenzymes
• Enzymes of glucose catabolism cannot function without their
coenzymes
• Two coenzymes of special importance to glucose catabolism
– NAD+ (nicotinamide adenine dinucleotide)
• derived from niacin (B vitamin)
• NAD+ + 2 H  NADH + H+
– FAD (flavin adenine dinucleotide)
• derived from riboflavin
• FAD + 2 H  FADH2
Overview of ATP Production
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Key
Glucose
Carbon atoms
ATP
Phosphate
groups
1 Phosphorylation
ADP
Glucose 6-phosphate
Glycogen
Fat
Fructose 6-phosphate
ATP
2 Priming
ADP
Fructose 1,6-diphosphate
3 Cleavage
2 PGAL
2 Pi
2 NAD+
2 NADH + 2 H+
4 Oxidation
2
2 ADP
2 H2O
2 ATP
2
5 Dephosphorylation
2 ADP
2 ATP
2
2 pyruvic acid
2 NADH + 2 H+
2 NAD+
End-products of
glycolysis are:
2 pyruvic acid + 2 NADH
+ 2 ATP + 2 H+
2
2 lactic acid
Figure 26.3
Anaerobic fermentation
Aerobic respiration
Aerobic Respiration
• Most ATP generated in mitochondria
– Oxygen required as final electron acceptor
• Pyruvate decarboxylated
– Combines with coenzyme A to enter matrix
• Occurs in two principal steps:
– Matrix reactions – controlling enzymes are in the fluid of the
mitochondrial matrix
– Membrane reactions - controlling enzymes are bound to the
membranes of the mitochondrial cristae
Mitochondrial Matrix Reactions
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Pyruvic acid (C3)
6
CO2
NAD+
7
NADH + H+
Acetyl group (C2)
8
Acetyl-Co A
Coenzyme A
H2O
9
Citric acid (C6)
Oxaloacetic acid (C4)
H2O
10
NADH + H+
NAD+
(C6)
Citric
acid
cycle
18
H2O
NAD+
11
NADH + H+
(C4)
12
CO2
17
(C5)
H2O
NAD+
13
Occurs in
mitochondrial
matrix
(C4)
14
16
FADH2
NADH + H+
(C4)
CO2
FAD
(C4)
Pi
15
GTP
ADP
GDP
ATP
Figure 26.4
Summary of Matrix Reactions
2 pyruvate + 6H2O  6CO2
2 ADP + 2 Pi  2 ATP
8 NAD+ + 8 H2  8 NADH + 8 H+
(2 NADH produced during glycolysis)
2 FAD + 2 H2  2 FADH2
• Carbon atoms of glucose have all been carried away as CO2 and
exhaled
• Energy lost as heat, stored in 2 ATP, 8 reduced NADH, 2 FADH2
molecules of the matrix reactions and 2 NADH from glycolysis
• Citric acid cycle is a source of substances for synthesis of fats and
nonessential amino acids
Membrane Reactions
• Membrane reactions have two purposes:
– to further oxidize NADH and FADH2 and transfer their energy
to ATP
– to regenerate NAD+ and FAD and make them available again
to earlier reaction steps
• Mitochondrial electron-transport chain – series of
compounds that carry out this series of membrane
reactions
Members of the Transport Chain
• Flavin mononucleotide (FMN) – derivative of riboflavin similar
to FAD
– bound to a membrane protein FMN accepts electrons from NADH
• Iron-sulfur (Fe-S) centers – complexes of iron and sulfur atoms
bound to membrane proteins
• Coenzyme Q (CoQ) – accepts electrons from FADH2
– small mobile molecule that moves about in the membrane
• Copper (Cu) ions – bound to two membrane proteins
• Cytochromes – five enzymes with iron cofactors
– brightly colored in pure form
– in order of participation in the chain, b, c1, c, a, a3
Electron Transport
• hydrogen atoms are spilt apart as they transfer from
coenzymes to the chain
• protons pumped into the intermembrane space
• electrons travel in pairs (2 e-) along the transport chain
• each electron carrier becomes reduced when it receives an
electron pair and oxidized again when it passes the electrons
along to the next carrier
• oxygen is the final electron acceptor
– each oxygen atom accepts two electrons from cytochrome a3 and two
protons from the mitochondrial matrix forming water
• body’s primary source of metabolic water – water synthesized in the body
– this reaction explains the body’s oxygen requirement
– no oxygen, cell produces too little ATP to sustain life
Electron Transport Chain
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50
NADH + H+
Relative free energy (kcal/mole)
40
NAD+
FADH2
Enzyme complex 1
F AD
Figure 26.5
30
1
20
Enzyme complex 2
10
½ O2 + 2 H+
Enzyme complex 3
0
Reaction progress
H2O
Chemiosmotic Mechanism
• electron transport chain energy fuels respiratory
enzyme complexes
– pump protons from matrix into space between inner and
outer mitochondrial membranes
– creates steep electrochemical gradient for H+ across inner
mitochondrial membrane
• inner membrane is permeable to H+ at channel
proteins called ATP synthase
• chemiosmotic mechanism - H+ current rushing back
through these ATP synthase channels drives ATP
synthesis
Chemiosmotic ATP Synthesis
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Intermembrane
space
Matrix
Cristae
Figure 26.6
Inner membrane
Outer membrane
NADH +
H+
½ O2 + 2 H+
NAD+
6 H+
H2O
Matrix
2e–
Inner
membrane
Enzyme
complex
1
CoQ
2e–
2e–
Enzyme
complex
2
Enzyme
complex
3
Cyt c
Intermembrane
space
Outer
membrane
2 H+
2 H+
2 H+
3 ADP + 3 Pi
3 ATP
ATP
synthase
Overview of ATP Production
• NADH releases an electron pair to electron
transport system and H+ to prime pumps
– enough energy to synthesize 3 ATP
• FADH2 releases its electron pairs further along
electron-transport system
– enough energy to synthesize 2 ATP
• complete aerobic oxidation of glucose to CO2 and
H2O produces 36-38 ATP
– efficiency rating of 40% - 60% is lost as heat
ATP Generated by Oxidation of Glucose
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Glucose
2
Glycolysis
ATP
(net)
2 NADH + 2 H+
Cytosol
2 pyruvate
Mitochondria
2 NADH + 2 H+
CO2
6 NADH + 6 H+
Citric acid
cycle
2 ATP
Figure 26.7
2 FADH2
Electron-transport
chain
O2
H2O
4 ATP
28–30
Total 36–38
ATP
ATP
Glycogen Metabolism
• ATP is quickly used after it is formed
– it is an energy transfer molecule, not an energy storage molecule
– converts the extra glucose to other compounds better suited for energy
storage (glycogen and fat)
• glycogenesis - synthesis of glycogen
– stimulated by insulin
– chains glucose monomers together
• glycogenolysis – hydrolysis of glycogen
– releases glucose between meals
– stimulated by glucagon and epinephrine
– only liver cells can release glucose back into blood
• gluconeogenesis - synthesis of glucose from noncarbohydrates,
such as glycerol and amino acids
– occurs chiefly in the liver and later, kidneys if necessary
26-20
Glucose Storage and Use
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Blood
glucose
Extracellular
Intracellular
Glucose
6-phosphatase
(in liver, kidney,
and intestinal cells)
Hexokinase
(in all cells)
Glucose 6-phosphate
Glycogen
synthase
Key
Pi
Glucose
1-phosphate
Glycogenesis
Glycogenolysis
Glycogen
Glycogen
phosphorylase
Glycolysis
Figure 26.8
Pi
Lipids
• Triglycerides are stored in body’s adipocytes
– constant turnover of lipid molecules every 2 - 3
weeks
• released into blood, transported and either oxidized or
redeposited in other fat cells
• Lipogenesis - synthesis of fat from other types of
molecules
– amino acids and sugars used to make fatty acids and
glycerol
– PGAL can be converted to glycerol
Lipids
• Lipolysis – breaking down fat for fuel
– begins with the hydrolysis of a triglyceride to glycerol and
fatty acids
– stimulated by epinephrine, norepinephrine, glucocorticoids,
thyroid hormone, and growth hormone
– glycerol easily converted to PGAL and enters the pathway of
glycolysis
• generates only half as much ATP as glucose
– beta oxidation in the mitochondrial matrix catabolizes the
fatty acid components
• removes two carbon atoms at a time which bonds to coenzyme A
• forms acetyl-CoA, the entry point for the citric acid cycle
– a fatty acid with 16 carbons can yield 129 molecules of ATP
• richer source of energy than the glucose molecule
Lipogenesis and Lipolysis Pathways
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Glucose
Glucose 6-phosphate
Stored
triglycerides
Glycerol
PGAL
Fatty acids
Glycerol
Beta oxidation
Pyruvic
acid
Fatty
acids
Acetyl groups
New
triglycerides
Acetyl-Co A
Ketone bodies
β-hydroxybutyric acid
Acetoacetic acid
Acetone
Citric
acid
cycle
Figure 26.9
Key
Lipogenesis
Lipolysis
Proteins
• amino acid pool - dietary amino acids plus 100 g of
tissue protein broken down each day into free amino
acids
• may be used to synthesize new proteins
– fastest rate of cell division is epithelial cells of intestinal
mucosa
• of all the amino acids absorbed by the small intestine:
– 50% comes from the diet
– 25% from dead epithelial cells
– 25% from enzymes that have digested each other
Proteins
• amino acids in the pool can be converted to others
• free amino acids also can be converted to glucose and fat or
directly used as fuel
• conversions involve three processes:
– deamination – removal of an amino group (-NH2)
– amination – addition of -NH2
– transamination – transfer of -NH2 from one molecule to another
• as fuel - first must be deaminated (removal of -NH2)
– what remains is keto acid and may be converted to pyruvic acid, acetylCoA, or one of the acids of the citric acid cycle
– during shortage of amino acids, citric acid cycle intermediates can be
aminated and converted to amino acids
– in gluconeogenesis, keto acids are used to synthesis glucose
Transamination, Ammonia, and Urea
• when an amino acid is deaminated
– its amino group is transferred to a citric acid cycle
intermediate, α-ketoglutaric acid, converting it to glutamic
acid
– glutamic acid can travel from any of the body’s cells to the
liver
•
•
•
•
here its -NH2 is removed converting back α-ketoglutaric acid
-NH2 become ammonia (NH3)
which is toxic and cannot accumulate
urea cycle – pathway by which the liver combines ammonia with
carbon dioxide to produce less toxic waste, urea
• urea excreted in the urine as one of the body’s nitrogenous wastes
Pathways of Amino Acid Metabolism
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Glucose
Pyruvic acid
Protein
Amino
acids
Keto
acids
Acetyl-CoA
Citric
acid
cycle
–NH2
-ketoglutaric
acid
NH3
Glutamic
acid
Urea
cycle
Urea
Urine
Figure 26.10
CO2
Liver Functions in Metabolism
• wide variety of roles in carbohydrate, lipid, and
protein metabolism
• overwhelming majority of its functions are
nondigestive
• hepatocytes perform all functions, except
phagocytosis
• See table 26.6
Metabolic States
• Metabolic rate
– Amount of energy liberated in the body per unit time
• Absorptive state
– Nutrients are being absorbed and my be used
immediately to meet needs
• Postabsorptive state
– Stomach and small intestines empty, energy needs
met from stored fuel