Transcript Slides - Websupport1

Anatomy & Physiology
SIXTH EDITION
Lecture 25: Metabolism and
Energetics
Lecturer: Dr. Barjis
Room: P313
Phone: (718) 260-5285
E-Mail: [email protected]
Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings
Frederic H. Martini
Fundamentals of
Learning Objectives
• Explain why cells need to synthesis new organic
components
• Describe the basic steps in glycolysis, the TCA
cycle, and the electron transport chain
• Summarize the energy yield of glycolysis and
cellular respiration
• Describe the pathways involved in lipid, protein
and nucleic acid metabolism
Learning Objectives
• Summarize the characteristics of the absorptive
and postabsorptive metabolic states
• Explain what constitutes a balanced diet and why
such a diet is important
• Define metabolic rate and discuss the factors
involved in determining an individual’s BMR
Metabolism
• Cells break down organic molecules to generate
energy (ATP)
• Energy is used for: growth, cell division,
contraction, secretion, and other functions
• Metabolism is all the chemical reactions that
occur in an organism
• Chemical reactions provide energy and maintain
homeostasis:
• metabolic turnover
• growth and cell division
• special processes, such as secretion, contraction, and
action potential propagation
An Introduction to Cellular Metabolism
Metabolism
• Metabolic reactions could be either catabolic
(catabolism) or anabolic (anabolism)
• Anabolism
• Anabolism is the formation of new chemical
bonds to produce new organic molecules
• New Organic molecules are needed for/to:
• Performance of structural maintenance and
repairs
• Support of growth
• Production of secretions
• Building of nutrient reserves
Metabolism
• Catabolism
• Catabolism is the metabolic reactions that
breaks down organic substrates in order to
release energy
• Catabolic reactions occur in series of steps
• Catabolic reactions generate energy by
breaking down large molecules to small
molecule
• Small molecules enter Mitochondria to
release more energy
Cells and Mitochondria
• Cells provide small organic molecules for their
mitochondria
• Mitochondria produce ATP that is used by the
cell to perform cellular functions i.e. cells feed
mitochondria nutrient and in return
mitochondria provide the cells with energy
(ATP).
• Mitochondria accept only specific organic
molecules e.g. Pyruvic Acid, acetyl coenzyme A
• Large organic nutrients (e.g. Glucose, fatty acid,
amino acids) are broken down into smaller
fragments (e.g. Pyruvic Acid) in the cytoplasm
Cells and Mitochondria
• Mitochondria breaks down the small fragments
to carbon dioxide, water, and generates more
energy (ATP) via two pathways:
• 1. TCA cycle
• 2. Electron transport system (ETS)
Nutrient Use in Cellular Metabolism
Carbohydrate Metabolism
Most cells generate ATP through the breakdown
of carbohydrates
• Glycolysis is the process of breakdown of glucose
into pyruvic acid
• Glycolysis occur in the cytoplasm and it requires:
• One molecule of glucose + 2 ATP + 4ADP + 2NAD +
inorganic phosphate + cytoplasmic enzymes
• Glycolysis generates:
• Two pryruvic acid + 4ATP +2ADP + 2NADH
• The net gain of ATP of glycolysis is 2ATP (it produces
4ATP but two of the ATP are used)
Carbohydrate Metabolism
Most cells generate ATP through the breakdown
of carbohydrates
• Aerobic metabolism (cellular respiration)
• Pyruvic acid will enter mitochondria and generate more ATP via
TCA cycle and ETS
• Two pyruvates = 34 ATP
• The chemical formula for this process is
C6H12O6 + 6 O2  6 CO2 + 6 H2O
• Anaerobic metabolism (fermentation)
• In the absence of oxygen pyruvic acid will not enter mitochondria
• Pyruvic acid will go through the process of anaerobic respiration
and will be converted into Lactic acid
• This process dose not generate any ATP
Glycolysis: Steps in Glycolysis
1)
Glucose (a 6 carbon molecule)
enters the cell
2)
As soon as glucose is inside the
cell, a phosphate is added to
carbon number 6, and the new
molecule is called glucose 6
phosphate. This reaction is
called phosphorylation and it
requires one ATP, enzyme
called hexokinase.
3)
Glucose 6 phosphate goes
through the second
phosphorylation reaction and a
phosphate is added to
carbonenumber 1. The new
molecule produced as a result is
called Fructose 1,6
Bisphosphate
4)
The Fructose 1,6 bisphosphate
(6 carbon molecule with
phosphate s attached to carbon
1 and carbon 6) will split into
two 3 carbon molecule:
5)
1)
Glyceraldehyde 3
phosphate
2)
Dihydroxyacetone
Each 3 carbon molecule will
become a pyruvic acid through
number of steps (see the
diagram on the left)
Mitochondrial ATP Production
(cellular respiration)
• The two pyruvic acid molecules will enter
mitochondria
• In the mitochondria pyruvic acid will join
Coenzyme A (CoA) to form acetyl CoA before
entering the TCA cycle.
• TCA cycle will break down pyruvic acid
completely
• Decarboxylation
• Hydrogen atoms passed to coenzymes
• Oxidative phosphorylation
The TCA Cycle Steps
1)
Pyruvic acid combine with
coenzyme A to form acetyl
coenzyme A. This reaction
releases NADH and carbon
dioxide
2)
Acetyl is a 2 carbon molecule.
Acetyl-coenzyme A will give the
two carbon molecule (acetyl) to
the 4 carbon molecule
(oxaloacetic acid)
3)
The 4 carbon molecule will
become a 6 carbon molecule
(citric acid)
4)
Citric acid will go through
number of steps and will become
back a 4 carbon molecule .
5)
The TCA cycle will begin with
formation of citric acid and end
with formation of oxaloacetic
acid.
6)
7)
The TCA cycle will run twice for
one molecule of glucose, because
one molecule of glucose
produces two pyruvic acid and
each pyruvic acid turns once
cycle
Each cycle of TCA will generate 3NADH, 1FADH2, and 1GTP
8)
NADH and FADH2 will enter the electron transport system and generate ATP
9)
One NADH = 3ATP and one FADH2 = 2ATP (see ETS)
The TCA Cycle
•
Pyruvic acid (a 3 carbon molecule) requires NAD and Coenzyme to form Acetyl
coenzyme A
•
This reaction will generate NADH, carbon dioxide and acetyl coenzyme
A. Notice that pyruvic acid is a 3 carbon molecule , in this reaction one
of the carbons was released as carbon dioxide is formed and two carbon
is left as a acetyl
•
Acetyl coenzyme A will transfer the acetyl to oxaloacetic (a 4
carbon molecule) acid and coenzyme A will becomee free. 4
carbon molecule from oxaloacetic acid and two carbon from acetyl
will generate a 6 carbon molecule (citric acid)
•
The free coenzyme A will be reused by another pyruvic acid.
•
Citric acid will go through number of steps (e.g. it will become
isocetric acid then ketoglutaric acid and so on)and eventually will
become oxaloacetic acid
The TCA Cycle
•
The free coenzyme A will be reused by another pyruvic acid.
•
Citric acid will go through number of steps (e.g. it will become isocetric acid
then ketoglutaric acid and so on)and eventually will become oxaloacetic acid
Oxidative phosphorylation and the ETS
• Requires coenzymes and consumes oxygen
• Key reactions take place in the electron transport
system (ETS)
• Cytochromes of the ETS pass electrons to
oxygen, forming water
• The basic chemical reaction is:
2 H2 + O2  2 H2O
Electron Transport System (ETS)
• ETS is sequence of proteins called cytochromes
• Each cytochrome has:
• A protein - embedded in the inner membrane
of a mitochondrion,
• A pigment
• STEP1: coenzyme strips a pair of hydrogen atoms from a
substrate molecule.
• STEP2: NADH and FADH2 deliver hydrogen atoms to
coenzymes embedded in the inner membrane of a
mitochondrion.
• STEP3: Coenzyme Q accepts hydrogen atoms from FMNH2
and FADH2 and passes electrons to cytochrome b.
• STEP4: Electrons are passed along the electron transport
system, losing energy in a series of small steps. The
sequence is cytochrome b to c to a to a3.
• STEP5: At the end of the ETS, an oxygen atom accepts the
electrons, creating an oxygen ion (O–). This ion has a very
strong affinity for hydrogen ions (H+); water is produced.
Oxidative Phosphorylation
Energy yield of glycolysis and cellular
respiration
• Per molecule of glucose entering these pathways
• Glycolysis – has a net yield of 2 ATP
• Electron transport system – yields
approximately 28 molecules of ATP
• TCA cycle – yields 2 molecules of ATP
The Energy Yield of Aerobic Metabolism
The Energy Yield of Aerobic Metabolism
The Energy Yield of Aerobic Metabolism
The Energy Yield of Aerobic Metabolism
The Energy Yield of Aerobic Metabolism
The Energy Yield of Aerobic Metabolism
The Energy Yield of Aerobic Metabolism
The Energy Yield of Aerobic Metabolism
The Energy Yield of Aerobic Metabolism
A Summary of the Energy Yield of Aerobic
Metabolism
Synthesis of glucose and glycogen
• Gluconeogenesis
• Synthesis of glucose from noncarbohydrate
precursors such as lactic acid, glycerol,
amino acids
• Liver cells synthesis glucose when
carbohydrates are depleted
• Glycogenesis
• Formation of glycogen
• Glucose stored in liver and skeletal
muscle as glycogen
• Important energy reserve
Carbohydrate Breakdown and Synthesis
Lipid catabolism
• Lipolysis
• Lipids broken down into pieces that can be
converted into pyruvate
• For example triglycerides are split into glycerol
and fatty acids
• Glycerol enters glycolytic pathways
• Fatty acids enter the mitochondrion
Lipid catabolism
• Beta-oxidation
• Breakdown of fatty acid molecules into
2-carbon fragments
• Lipids and energy production
• Used when glucose reserves are limited
Beta Oxidation
•
In beta oxidation long chain of fatty acids are broken down
into fragments of two carbons.
•
Say we have a fatty acid chain that is 18 carbon long.
During beta oxidation fragments of two carbon will be
removed from the chain of fatty acid. So after the first
round of reaction (as shown in the figure) a fatty acid chain
that is 16 carbon long will remain, after the second round
of reactions a fatty acid chain that 14 carbon long will
remain
•
For each round of reaction two carbon will be removed
from the chain. As two carbons are removed from the
chain, NADH, FADH2 and Acetyl CoA will be generated.
•
The steps in beta oxidation:
1)
2)
Coenzyme A bind to fatty acid. This step requires
one ATP
This reaction will prepare fatty acid for beta oxidation
and generate a fatty acid attached to CoA
Beta Oxidation
3) The first round of beta oxidation will generate one
NADH, one FADH2 and one Acetyl CoA
4) Acetyl CoA will enter TCA cycle and generate 3NADH,
1FADH and 1GTP. 3NADH = 9ATP, 1FADH2 =
2ATP, and GTP = 1ATP.
Beta Oxidation
5)
NADH and FADH2 will enter the ETS and generate
ATP
1NADH = 3ATP
1FADH2 = 2ATP
Summary :
one round of beta oxidation will generate :
NADH = 3ATP
FADH2 = 2ATP
Acetyl CoA = 12ATP
So if each round of beta oxidation produces 17ATP,
then one molecule of fat will produce a lot more ATP
(energy) than one molecule of glucose. Remember
that glucose produced 2ATP in glycolysis and
34/36ATP via TCA and ETS
Lipid synthesis (lipogenesis)
• Non essential fatty acids are the fatty acids that
can be synthesized
• Essential fatty acids are fatty acid that cannot be
synthesized and must be included in diet
• Example of essential fatty acids include:
• Linoleic and linolenic acid
Lipid Synthesis
Lipid transport and distribution
• Lipoproteins are lipid-protein complex that contains large
glycerides and cholesterol
• 5 types of lipoprotein
1) Chylomicrons
• Largest lipoproteins composed primarily of triglycerides
• Delivers lipids from digestive tract (intestine) to liver
2) Very low-density lipoproteins (VLDLs)
• Contain triglycerides, phospholipids and cholesterol
• Delivers triglycerides to the cells
• Lipoprotein lipase (enzyme) in the capillaries break the triglyceride into
monoglyceride and fatty acid for use by the cell
• Steps:
• VLDL containing triglyceride is released into blood circulation by the liver
• When VLDL gets to the capillaries, an enzyme called lipase break the
triglycerides into monglyceride and free fatty acid
• The monoglyceride and free fatty acid are used by the cell
• VLDL is left with less triglyceride so it is called IDL
Lipid transport and distribution
3) Intermediate-density lipoproteins (IDLs)
• Contain smaller amounts of triglycerides
• Return remaining triglycerides back to the liver
• When the IDL arrives into the liver, the livers adds cholesterol to IDL. Once
cholesterol is added to the IDL, it would be called LDL
4) Low-density lipoproteins (LDLs) – also called the bad cholesterol
• Contain mostly cholesterol
• LDL is released into the blood stream by the liver
• LDL delivers cholesterol to the cells
• The cell uses the cholesterol for synthesis of membrane, hormones and other
material
• Any excess cholesterol that is not used by the cell will diffuse out of cell back into
capillaries (circulation)
5) High-density lipoproteins (HDLs) also called the good cholesterol
• HDL collects the extra cholesterol that diffuses out of the cell and delivers them
back to the liver
• The liver reuses the cholesterol to make LDL, and excretes any excess cholesterol
with bile
Lipid Transport and Utilization
Lipid Transport and Utilization
Protein Metabolism
Amino acid catabolism
• If other sources inadequate, mitochondria can break down
amino acids
• TCA cycle
• The first step in amino acid catabolism is the removal of the
amino group (-NH2)
• The amino group is removed by transamination or
deamination
• Transamination – attaches removed amino group to a
keto acid
• Deamination – removes amino group generating NH4+
• Proteins are an impractical source of ATP production
Amino Acid Catabolism: Transamination
• Attaches the amino group of an amino acid to a keto acid
•
Transamination converts the keto acid into an amino acid that can
enter the cytosol and be used for protein synthesis
• Reactions enable a cell to synthesize many of the amino acids
needed for protein synthesis
Amino Acid Catabolism: Deamination
Deamination preparing an amino acid for breakdown in the TCA
cycle
Deamination removes an amino group of an amino acid and
enerates an ammonia (NH3) molecule or an ammonium ion (NH4+).
Ammonia molecules are highly , thus liver (the primary site of
deamination) has enzymes that converts the ammonia to urea
Amino Acid Catabolism
Protein synthesis
• Essential amino acids
• Cannot be synthesized by the body in adequate
supply
• Nonessential amino acids
• Can be synthesized by the body via amination
• Addition of the amino group to a carbon
framework
Nucleic acid metabolism
• Nuclear DNA is never catabolized for energy
• RNA catabolism
• RNA molecules are routinely broken down and
replaced
• Generally recycled as nucleic acids
• Can be catabolized to simple sugars and
nitrogenous bases
• Do not contribute significantly to energy
reserves
Body has five metabolic components
• Liver
• The focal point for metabolic regulation and
control
• Adipose tissue
• Stores lipids primarily as triglycerides
• Skeletal muscle
• Substantial glycogen reserves
Body has five metabolic components
• Neural tissue
• Must be supplied with a reliable supply of
glucose
• Other peripheral tissues
• Able to metabolize substrates under endocrine
control
Vitamins
• Are needed in very small amounts for a variety of
vital body activities
• Fat soluble
• Vitamins A, D, E, K
• Taken in excess can lead to hypervitaminosis
• Water soluble
• Not stored in the body
• Lack of adequate dietary intake = avitaminosis
You should now be familiar with:
• Why cells need to synthesis new organic
components
• The basic steps in glycolysis, the TCA cycle, and
the electron transport chain
• The energy yield of glycolysis and cellular
respiration
• The pathways involved in lipid, protein and
nucleic acid metabolismBMR
You should now be familiar with:
• The characteristics of the absorptive and
postabsorptive metabolic states
• What constitutes a balanced diet and why such a
diet is important
• Metabolic rate and the factors involved in
determining an individual’s BMR