Transcript Metabolism

Metabolism
“Life is all about shaping new molecules
from old.”
-Robert Thornton, Chemistry of Life (CD-ROM)
Outline
• I.
Metabolism basics
• Reaction types, enzymes, electron acceptors, cellular location
• II. Breakdown of glucose (Carbs)
• Glycolysis, Kreb’s cycle, electron transport chain
• II. Breakdown of fat
• Lipolysis, Fatty acid oxidation
• III. Breakdown of protein
• Proteolysis, Deamination
• IV. Energy from protein
• V. Synthesizing macronutrients
• Gluconeogenesis, Lipogenesis
• VI. Feasting vs. Fasting
• Metabolism—encompasses all of the chemical
changes that occur in living organisms.
• Metabolic pathway—describes a series of
chemical reactions that either break down or
build molecules
Types of Metabolic pathways
• Catabolic—describes the break down of a
large molecule into smaller units
• Anabolic—describes the building of more
complex molecules from smaller ones
Metabolism
Copyright 2004 Pearson education, Inc. published by Benjamin Cummings
Figure 7.1
Adenosine Triphosphate (ATP)
•ATP is an organic compound used by cells as a
source of energy
– Energy is stored in the phosphate bonds
– When the bonds are broken, they release energy
– This energy is used to do work of the cell
Adenosine Triphosphate (ATP)
Copyright 2004 Pearson education, Inc. published by Benjamin Cummings
Figure 7.2
Condensation & Hydrolysis
•Condensation is an anabolic process
– Water is released as a by-product
– A—OH + H—B  A—B + H20
•Hydrolysis is usually a catabolic process
– A large molecule is broken apart with the addition
of water
– A—B + H20  A—OH + H—B
Phosphorylation
•Phosphorylation is the addition of phosphate
group to a compound
•When the 2 high-energy phosphate bonds in
ATP are hydrolyzed
– energy is released
– phosphate is transferred to other molecules
•When glucose is phosphorylated, it can be
oxidized for energy or stored as glycogen
Oxidation-Reduction Reactions
•Molecules exchange electrons (hydrogen)
•Exchange reactions occur together
•Molecule giving up an electron is “oxidized”
– Its electron is removed by oxygen
•Molecule receiving an electron is “reduced”
– In gaining an electron, it becomes more negatively
charged
Enzymes
• Enzymes are the protein “machines” that take
molecules apart and reassemble them
–
–
–
–
Isomerases
Dehydrogenases
Hydrogenases
Transferases, etc.
• About ~50% of all proteins are enzymes
• Enzymes work by lowering the activation
energy of a reaction
Coenzymes
• Vitamins are organic coenzymes
• Lack of vitamins can prevent certain chemical
reactions from occurring and can result in
disease:
Coenzyme
Function
Vitamin D
Calcium metabolism, bone formation
Vitamin A
Night vision
Niacin
Carries electrons in cellular respiration
Cofactors
• Some enzymes require cofactors to function
• Cofactors are typically minerals
• Cofactors bind to enzymes, thus rendering
them active.
Cofactor
Enzyme
Zinc
Alcohol dehydrogenase
Iron
Cytochromes
Sodium
ATPases
Where does metabolism take place?
http://cellbio.utmb.edu/cellbio/mitmor4.jpg
Marieb, EN and Mallat, J. Human Anatomy. 2nd ed. Menlo Park, Calif.: Benjamin Cummings, c1997
Different macromolecules have
different metabolic pathways…
Energy from Carbohydrates
•When glucose is transported to the liver, it is
– Phosphorylated and metabolized for energy or stored as
glycogen
– Released into circulation for other cells to use as fuel or
stored as glycogen (muscle tissue)
– Converted to fatty acids, if glucose exceeds caloric needs,
and stored as triglycerides in adipose tissue
•Fructose and galactose are converted to glucose in the
liver and follow the same fate
I. Cellular Respiration
The breakdown of a glucose molecule
• Made of three different metabolic pathways:
Pathway
Location
ATP produced per
glucose molecule
Glycolysis
Cytosol
2 ATP
Citric Acid Cycle
(aka Kreb’s cycle)
Mitochondrial matrix
2 GTP
Chemiosmosis
(aka ETC)
Inner mitochondrial
membrane
22-30 ATP
Who are the key energy players?
Re-introducing….
• ATP! Adenosine triphosphate
…and the electron acceptors
• NAD: Nicotinamide adenosine diphosphate
• Derivative of the B vitamin Niacin
• Accepts 1-2 high energy electrons to form
NADH or NADH + H+
• FAD: Flavin adenine diphosphate
• Derivative of the B vitamin riboflavin
• Accepts 2 high energy electrons to form FADH2
Glycolysis
• GlucosePyruvate
• Occurs in the cytosol
• Is an anaerobic process
• Energy yield2 ATP + 2 NADH
Glycolysis
In the Absence of Oxygen…
Copyright 2004 Pearson education, Inc. published by Benjamin Cummings
Figure 7.7a
In the Absence of Oxygen…
Copyright 2004 Pearson education, Inc. published by Benjamin Cummings
Figure 7.7b
In the Presence of Oxygen…
Copyright 2004 Pearson education, Inc. published by Benjamin Cummings
Figure 7.8
PyruvateAcetyl CoA
• Aerobic reaction
• Occurs in mitochondria
• Converts pyruvate to Acetyl CoA
• 2 pyruvate molecules from glycolysis yields 2
NADH and 2 Acetyl CoA molecules
Kreb’s Cycle (Citric Acid Cycle)
• Completes the metabolic breakdown of
glucose to ATP, CO2
• Energy yield 2 GTP + 8 NADH + 2FADH2
Krebs Cycle
Copyright 2004 Pearson education, Inc. published by Benjamin Cummings
Electron Transport Chain
• Composed of proteins and cytochromes lined
in the inner mitochondrial membrane
• Electrons are transferred through the chain,
releasing energy to pump H+ into the
intermembrane space and eventually
producing ATP
• Energy yield about 22-30 ATPs
Electron transport chain
Insel, Turner and Ross. Nutrition, c2002
Summary of Glucose oxidation
Net energy gain from one glucose molecule=
36-38 ATP
Take a breather.
II. Breakdown of FAT
• Enzymes break down triglycerides into their
component parts, glycerol and fatty acids
Then what?
• Glycerol is converted to pyruvate or glucose by the
liver
• Fatty acid contains nearly all the energy
• Fatty acids must be activated—linked to coenzyme A
before it can enter catabolic pathways.
• This activation happens in the cytosol and costs 1 ATP
(ATPAMP +2Pi)
Carnitine Shuttle
• Fatty acid oxidation takes place in the
mitochondria
• Fatty acids rely upon carnitine to ferry them from
the cytosol into the mitochondria
• Carnitine deficiency can slow production
of ATP (heart/skeletal muscle can lose
endurance)
Beta oxidation
• In the mitochondria, beta oxidation disassembles the
fatty acids and converts it into molecules of acetyl CoA
• Enzymes clip a 2-carbon link from the end of the chain.
• As the chain is shortened, 1 FADH2 and 1 NADH form,
and the 2-carbon link becomes acetyl CoA
• The acetyl CoA enters Kreb’s cycle and eventually the
electron transport chain (just like glucose)
• Fatty acids usually produce substantially more ATP than
glucose
To burn fat, you need carbohydrates!!!
• Acetyl CoA from beta-oxidation can not start
the citric acid cycle without a steady supply of
oxaloacetate
• Starvation and very-low carb diets can deplete
oxaloacetate
• This reroutes the acetyl CoA to form ketone
bodies
Ketoacidosis
• Ketogenesis (production of ketone bodies) occurs when
abundance of acetyl CoA overwhelms available supply
of oxaloacetate
• Ketones are a type of emergency energy to the body’s
tissues
• Liver makes ketone bodies (3 types) from acetyl coA,
travels through bloodstream to other tissues
• The ketone Acetoacetate can be converted back into
acetyl coA, but with low levels of OAA,
Formation of ketone bodies
Ketoacidosis
• Kidneys excrete excess ketone bodies in urine
and lungs exhale them
• Ketosis occurs when removal process can’t
keep up
• Blood levels of ketones rises, altering the pH
• Can result in brain damage and eventually,
death
What everyone wants to know…
How do we store Fat?
• Fatty acids are stored as triglycerides
• High fat diets: most go to straight to fat stores
• High protein diets: body converts most of
excess protein to fat
• High carb diets: does not convert protein to
fat; however, it shifts your body’s fuel
preferences to burn more carbs than fat
III. Breakdown of proteins
• Proteins are only used for energy in the
absence of fat or carbs
• Carbon skeletons: are formed by the
deamination of amino acids and can enter the
metabolic pathways at several points
depending on their structure (# carbons)
Energy from Protein
•During starvation, the body turns to its own
tissues for energy
Figure 7.19
Breakdown of proteins
• Glucogenic Amino Acids: become pyruvate or
a Kreb’s cycle intermediate
• Ketogenic Amino Acids: become acetyl CoA
• The carbon skeleton’s point of entry
determines the amount of ATP produced
Energy from Protein
Figure 7.20
Energy from Protein
+
•Ammonia from
protein catabolism
– Used as nitrogen source for synthesis of
nonessential amino acids
– High levels are toxic
– Liver converts ammonia to less toxic urea
NH3
Ammonia
Liver
NH3
Ammonia
CO2
O
H2N
C
Urea
NH2
Urea is
transported
to kidneys via
bloodstream
Kidney
Urea is excreted
in urine by
kidneys
Energy from Protein
•The body prefers using carbohydrates and fat
for energy
•Protein is reserved for metabolic functions that
cannot be performed by others
– building and repairing body tissues
•Protein are used for fuel primarily during low
total energy or carbohydrate intake
Energy from Protein
•Dietary proteins are digested into amino acids
or small peptides
•Amino acids are transported to the liver
– made into proteins
– released into the blood for uptake by other cells
for building and repair functions
•Excess dietary protein
– used for energy or converted to fatty acids for
storage as triglycerides
Stored Energy
•Stored energy can be used during times of
sleep, fasting, or exercise
•Extra energy is stored as
– Carbohydrate in limited amounts as liver and
muscle glycogen
– Fat (triglycerides) in unlimited amounts
•The body has no mechanism for storing amino
acids or nitrogen
Synthesizing Macronutrients
•Gluconeogenesis: making glucose from
nonglucose substrates
– Primarily from amino acids
– Small amount from glycerol (triglyceride)
– Maintains blood glucose during sleep, fasting,
illness, and exercise
•Protein catabolism for glucose production can
draw on vital tissue proteins (skeletal and heart
muscles and organ proteins)
Synthesizing Macronutrients
•Lipogenesis or de novo synthesis: making fat
from nonfat substances such as carbohydrates,
amino acids, and alcohol
– Occurs when consuming excess calories
– Acetyl CoA units assemble into fatty acid chains
– Fatty acids combine with glycerol to form
triglycerides
– Mostly occurs in liver cells
Feasting
Fasting
From FOOD energy to CELL energy!
Stage I
• Digestion, absorption, and transport
Stage II
• Breakdown of small molecules to metabolites
Stage III
• Transfer of energy to a usable form for cells