Transcript Chemical Energy Production

Metabolism
• Definition: Sum of all chemical reactions
in the body
• Anabolic versus Catabolic Reactions
– Anabolic Rxns = use chemical energy to
synthesize products
– Catabolic Rxns = break down substances to
generate chemical energy
Chemical Energy Production
Energy
(sunlight)
Photosynthesis
(plants)
CO2 + H2O
Carbohydrates + O2
Respiration
(animals and plants)
Carbohydrates + O2
CO2 + H20 + ATP
Food Consumption
Food ingested is digested to elementary
units by catabolic reactions that convert:
a. Lipids to glycerol and fatty acids
b. Proteins to amino acids
c. Complex carbohydrates to simple
sugars
Food Utilization
Elementary units (glycerol, f.a., a.a., simple
sugars) produced by digestion and absorption are:
a. used for energy production
b. stored
c. converted to other cellular products
d. used for production of other cell
components
Carbohydrate Metabolism
• Carbohydrates can be used to generate
ATP
• Can be stored as glycogen
– mostly in liver and skeletal muscle tissue
• Can be converted to fat and stored
Fat Metabolism
• Triglycerides are used to generate energy (ATP)
– F.A. generate acetyl Coenzyme A which enters Kreb’s
cycle and generates ATP
– At rest, @ half of energy used by muscle, liver and
kidneys comes from f.a. catabolism
• Glycerol can be converted to glucose
– Anaerobic and/or aerobic metabolism of glucose can
generate ATP
– Glucose can be converted to fat and stored
Fat Metabolism (continued)
• Can be stored as fat
– Accounts for majority of energy stored in body
– Most cells can store some fat
• Adipocytes = specialized cells designed for
storing fat
• Body will preferentially convert reserves to fat
for storage because gram per gram, fat
generates more energy than does protein or
carbohydrate
Protein Metabolism
• Proteins broken down to amino acids
• Amino acids can be used to generate ATP
– the amino group cannot be used to generate
ATP
– the remainder of most amino acids can
generate intermediates that can enter the
glycolytic pathway or the Kreb’s cycle
H O
H - N - C - C - OH
H R
Protein Anabolism
• Nonessential amino acids are those that can be
synthesized by the body
– glucose and fats can be used to generate
some amino acids
• Essential amino acids (8) cannot be synthesized
in body
– must be obtained from dietary intake
Energy Considerations
• Catabolic reactions release energy
– Majority released as heat energy
• Homeostasis strives to maintain constant
internal environment, including constant
internal temperature
• Pathways combine multiple reactions,
each of which generates small amounts of
energy, to minimize heat generation
Metabolic Pathway
• Definition: A sequence of enzymemediated reactions leading to the
formation of a particular product
• Mechanism for controlling thermal
energy release associated with chemical
reactions
Anaerobic versus Aerobic
Energy Production
• Anaerobic Metabolism
• Aerobic Metabolism
– DOES NOT Require oxygen
– Occurs in cytoplasm
– Converts glucose to pyruvate
by glycolysis
– DOES require oxygen
– Occurs in mitochondria
– Converts pyruvate to Acetyl
CoA
• Generates ATP
• Generates much lower levels
of ATP than aerobic
metabolism of glucose
• Generates ATP via the
Kreb’s cycle and electron
transport chain
• Generates much more ATP
than anaerobic metabolism
Chemical Oxidation & Reduction
• GER = GAIN OF ELECTRONS
– gain of an electron equivalent to gain of H
atom
– when a molecule gains electrons it becomes
REDUCED
• LEO = LOSS OF ELECTRONS
– loss of electron equivalent to loss of H atom
– when molecule loses electrons it becomes
OXIDIZED
NAD and FAD
• NAD = nicotinamide adenine dinucleotide
– derived from vitamin B3
• FAD = flavin adenine dinucleotide
– derived from vitamin B2
• Participate in oxidation/reduction reactions
– NAD and FAD are coenzymes for several reactions in
the Kreb’s cycle
– Become ‘reduced’ when they accept H atoms
– Become ‘oxidized’ when they donate their H atoms
• Shuttle hydrogen atoms between molecules by
vacillating back and forth between oxidized and
reduced forms
NAD and ATP Production
• Oxidized form = NAD+
• Reduced form = NADH + H+
• Each molecule of reduced NAD (NADH
+ H+) formed produces 3 ATP by
oxidative phosphorylation in the
mitochondria
FAD and ATP Production
• Oxidized form = FAD
• Reduced form = FADH2
• Each reduced FAD (FADH2) formed produces
2 ATP by oxidative phosphorylation in the
mitochondria
• 2 FADH2 produced in Kreb’s cycle (one per
molecule of pyruvate)
– produces 4 molecules of ATP by oxidative
phosphorylation
Phosphorylation
• Definition: Addition of phosphate group to an
organic molecule
• Two types of phosphorylation
– Substrate level
• The process of transferring a phosphate group between two
organic molecules
– i.e. make ATP by transferring a phosphate group from some
organic molecule to ADP to form ATP
– Oxidative
• The process of adding an inorganic phosphate to an
organic molecule
– i.e. make ATP by adding a free phosphate group (unattached
to any organic molecule) to ADP
Oxidative Phosphorylation
• Formation of ATP by adding inorganic
phosphate to ADP
• Occurs in mitochondria
• Energy used to drive the production of ATP
comes from the production of water (H2O) by
the combining of H atoms and oxygen
• H + O2
• ADP + Pi
H2 O
ATP
• Reduced NAD and FAD provide the H atoms
that combine with oxygen to form water
Glycolysis
• Conversion of glucose
– one 6-carbon sugar
pyruvate
two 3-carbon molecules
• Occurs in the cytoplasm
• USES 2 ATP molecules
– transfers 2 phosphates from ATP to ‘trap’ glucose and
later intermediates inside the cell
• Gross ATP production = 10 ATP
• Net ATP production = 6 ATP per molecule of
glucose utilized (8 ATP in heart and liver)
Gross ATP Production by
Glycolysis
• 4 ATP by substrate-level phosphorylation
(SLP)
• 6 ATP by oxidative phosphorylation (OP)
– 2 molecules of reduced NAD (NADH + H+)
– 3 ATP per molecule of reduced NAD
• Gross ATP = ATP by SLP + ATP by OP
– Gross ATP = 4 + 6 = 10 ATP
Glycolysis and ATP
Consumption
• 2 ATP molecules used for each molecule of
glucose converted to pyruvate
– One to trap glucose inside cell
– One to energize intermediate
• 2 ATP molecules used to supply energy to
transport reduced NAD to mitochondria
– Exception: liver and heart, which move reduced
NAD to mitochondria by non-ATP dependent
process
Net ATP Production by
Glycolysis
• Net ATP = Gross ATP produced – ATP
used
• In Most Tissues = 10 – 4 = 6 ATP
• In liver and heart = 10 – 2 = 8 ATP
Fate of Pyruvate Generated in
Glycolysis
• If oxygen is present pyruvate is converted
to Acetyl CoA
– 1 molecule glucose yields 2 molecules
pyruvate in glycolysis and so can produce 2
molecules of Acetyl CoA
– Acetyl CoA enters mitochondria and is
shuttled into the Kreb’s cycle
• If oxygen is absent pyruvate is converted
to lactate and handled by Cori cycle
Kreb’s Cycle
•
•
•
Occurs in mitochondria
Acetyl CoA feeds into cycle that
1. Generates 3 reduced NAD and 1
reduced FAD per revolution
-reduced NAD yields 9 ATP per revolution
-reduced FAD yields 2 ATP per revolution
2. Generates one ATP by substrate-level
phosphorylation per revolution
Two revolutions occur per molecule glucose
metabolized
ATP Production via Kreb’s Cycle
• Per revolution = 12 ATP
– 11 ATP by oxidative phosphorylation
– 1 ATP by substrate level phosphorylation
• Two revolutions per glucose molecule
yields 24 (I.e. 12 X 2 = 24) ATP total per
molecule of glucose metabolized via Kreb’s
cycle
ATP per glucose molecule
Anaerobic Metabolism
• By glycolysis
– 4 by SLP
– 6 by OP
• Gross = 10 ATP
• Net = 6 (or 8 in liver and
heart) ATP
– 2 used to trap and
energize
– 2 used to transport
reduced NAD to
mitochondria (except in
liver and heart)
Anaerobic Metabolism
• 6 (8 in liver and heart)
by glycolysis
• 6 by OP in conversion of
pyruvates to Acetyl CoA
• 24 by Kreb’s cycle
– 22 by OP
– 2 by SLP
Cori Cycle
• In the absence of oxygen, pyruvate is
converted to lactate (lactic acid)
• Cori cycle = cycle by which lactate is
handled in the body
Cori Cycle
• Lactate moves from muscle to blood;
pyruvate cannot leave muscle
• Lactate moves from blood to liver
– in liver, lactate is converted back to pyruvate
– pyruvate is converted back to glucose
– glucose can enter bloodstream and return to
muscle for energy production or be stored in
liver as glycogen
Cori Cycle
MUSCLE
BLOOD
Glycogen
Glucose
Glycogen
Glucose
Pyruvate
Lactate
LIVER
Glucose
Pyruvate
Lactate
Lactate
Metabolic States
• Absorptive state
– period when ingested nutrients are entering
the bloodstream from the G.I. Tract
– takes around 4 hours to completely absorb
average meal
• Post-absorptive state
– period when G.I. tract is empty of nutrients
and energy must be supplied by body’s
stored reserves
Absorptive State
• Glucose = major energy source
• Blood glucose levels high
• Insulin secreted from beta cells of pancreas
– insulin = protein hormone
– stimulates transport of glucose from bloodstream
into cells
• all cells except brain and liver require insulin action to
move glucose into cells
• Net synthesis of glycogen, fat, and protein
occurs
Insulin Actions in Liver
• Glucose can enter liver cells without insulin
• Promotes conversion of glucose to glycogen
(storage form of carbohydrates)
• Promotes conversion of fatty acids and amino
acids to fat
Insulin Action in Muscle
• Essential for transport of glucose into
cells
– skeletal muscle = majority of body mass and
major consumer of metabolic fuel, even at
rest
• Promotes conversion of glucose to
glycogen
Insulin Action in Fat
• Promotes uptake of glucose from
bloodstream
• Promotes conversion of glucose and fatty
acids to fat (triacylglycerols)
Insulin Action in Most Cells
• Promotes uptake of glucose from
bloodstream and use for energy (ATP)
production
• Promotes uptake of fatty acids and their
use for energy (ATP) production
• Promotes uptake of amino acids and their
conversion to protein
Glucose and the Brain
• Glucose can enter brain without insulin
action
– Brain cannot synthesize or store enough
glucose to provide energy from ATP for
more than a few minutes
• Body strictly regulates blood glucose to
meet brain’s needs
Post-absorptive State
•
•
•
•
Several hours after a meal
Blood glucose levels are low
Body must obtain glucose from reserves
Glucagon = main hormone in circulation,
produced by alpha cells of pancreas
Post-absorptive State (continued)
Catabolic reactions occur to:
1. Provide blood glucose
a. Glycogen converted to glucose
b. Gluconeogenesis = production of
glucose from non-carbohydrate
sources (i.e. Cori cycle lactate to
glucose)
2. Promote glucose sparing (preferential
use of fat over glucose in most tissues)
Actions of Glucagon in Liver
• Stimulates glycogenolysis (glycogen to
glucose)
• Stimulates fats to fatty acids
• Stimulates proteins to amino acids
Glucagon Action in Fat
Stimulates fat conversion to fatty acids
Glucagon Action in Most Cells
Stimulates protein conversion to amino
acids
Sources of Glucose
• Intestinal absorption
• Glycogen breakdown (glycogenolysis)
• Biosynthesis from non-carbohydrate
sources (gluconeogenesis)
• Most cells can synthesize glycogen from
and hydrolyze glycogen to glucose
• Only LIVER and KIDNEY can release
glucose into bloodstream
Enzymes and Glucose
Metabolism
• Insulin and Glucagon
• Glycogen Synthetase
– needed to synthesize glycogen from glucose
– found in most cells
• Phosphorylase
– needed to hydrolyze glycogen to glucose
– found in most cells
Enzymes and Glucose
Metabolism
• Pyruvate carboxylase,
phosphoenolpyruvate, and fructose 1,6
diphosphatase
– enzymes needed for gluconeogenesis
– found only in liver and kidney
• Glucose-6-phosphatase
– needed to release glucose into circulation
– found only in liver and kidney
Liver and Glucose Production
• Liver can produce glucose by gluconeogenesis
• Liver can release synthesized glucose for use by
other cells
• When liver is producing and releasing glucose
for use by other tissues it uses ketone bodies as
source of energy
– metabolic products produced by acetyl CoA
– acetoacetate, b-hydroxybutyrate, and acetone
Caloric Content of Major Food
Groups and Ethanol
Group
carbohydrate
protein
fat
ethanol
cal/gm
4
4
9*
7
*fat provides most energy per unit weight of all
foods; is best storage form of food
Exercise and Metabolism
• At rest
– skeletal muscle uses fatty acid metabolism to
provide energy
– blood glucose is reserved primarily for brain
• Exercise increases glucose utilization by
muscle
Exercise and Metabolism
(continued)
• Endogenous glucose production
increased to meet demands of low
intensity exercise
• Exhaustive high demand exercise
– first depletes glycogen stores
– then depletes liver-derived glucose
– eventually results in utilization of fatty acids
Regulation of Food Intake
• Hypothalamus
– site of feeding center (on switch for food intake)
– site of satiety center (off switch for food intake)
• Leptin
– protein hormone produced by fat cells
– acts at level of hypothalamus to decrease food intake
– may be part of negative feedback loop that monitors
body fat levels (lipostat)
Set-Point Theory
• ‘Predetermined’ weight optimum
– body strives to maintain setpoint and will defend
attempts to alter it (i.e. diets)
• Rhythm method of ‘girth’ control
– repeated cycles of alternating weight gain followed
by weight loss
– when body has reason to anticipate episodes of
starvation it adjusts metabolic processes to more
efficiently absorb and store food when it is available