METABOLISM
Lecture Notes:
I.Major absorbed nutrients
1. Glucose
a) --major body
fuel molecule, oxidized to convert ADP to ATP
b) building block for interconversion
into other molecules
2. Glycerol and
fatty acids, other fat molecules a)
major fuel for skeletal muscle (fatty acids)
b)
Phospholipids=cell membranes, myelin sheath
c) Cholesterol = bile,
cell membranes, steroid hormones
3. Amino Acids
a) Structural proteins,
(e.g., collagen, elastin)
b) Contractile protein (e.g., myosin, actin)
c) Enzymes
d) Hormones
e) Respiratory molecules
(e.g., Hemoglobin)
4. Vitamins
-coenzymes act with enzyme
to transfer energy from one molecule to another, (e.g., FAD, NAD from Riboflavin
and Niacin vitamin-)
5. Minerals--inorganic
molecules (Ca+, PO4=, K+, SO4=, Na+, Cl-)
a) Fe in hemoglobin
b) Na+, K and Cl- as electrolytes
d) Ca++ /PO4 for bone, Phophate also for formation of nucleic acids and ATP
6. Water
a) used in hydrolytic reactions
b) lubrication in serous membranes
c) transport of substances in fluids
Describe
how each major nutrient is used in the body.
II. Metabolism overview
all reactions in body = balance between energy-requiring (anabolism) and energy-releasing
(catabolism) reactions.
A. Anabolism (energy-requiring
reactions)
1. Reactions that combine
smaller, simpler molecules into larger molecules using energy from energy molecules
monosaccharide
+monosaccharide = polysaccharide + H2O
amino
acid + amino acid = proteins + H2O
glycerol
+ fatty acids =triglyceride lipid + H2O
nucleotides
+ nucleotides = nucleic acid + H2O
require energy to make bonds
B.
Catabolism (energy-releasing reactions) 1.
Breakdown of absorbed nutrients into smaller molecules
release energy from
bonds
Energy released from catabolic
reactions is transferred to ATP (adenosine triphosphate) which is used
to energize anabolic reactions or to do cell work (enzyme activity, transport
ions, muscle contraction, etc).
Most energy released in
catabolism is lost as heat to environment (as much as 90% in some organisms)
need to eat energy molecules (external fuel supply) to keep body sustained
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Compare
and contrast anabolism and catabolism in terms of reactant molecuse size as
well as use/release of energy and water.
C. Enzymes
1. Proteins structurally
shaped to accelerate reactions
2. Act as catalysts.
3. Enzymes are specific
to the molecules they work on ( substrate)
4. Most enzymes are two
parts
a. Apoenzyme are
the main part and act to catabolize or anabolize the major substrate.
b. Coenzymes generally
used for transfering energy
i.e., NAD, FAD (oxidized coenzymes) are not energetic
i.e., NADH2, FADH2 (reduced
coenzymes) ARE energetic
II. Enzyme mediated reaction
pathways (Black box approach)
Emphasize substrates going into enzymatic pathway and products leaving pathway.
A. types of reactions in enzymatic pathways
1. Oxidation/reduction
reactions (add/subtract 2H)
energy in energy molecule
is transferred to reduced coenzyme.
a. Oxidation (remove pair
hydrogen atoms from molecule)
energy in bond of high energy fuel molecule is released with hydrogen atoms
( leaving a lower energy molecule)
b. Reduction (add pair hydrogen atoms) energy
and atoms from above reaction are added to coenzyme
(NAD) to make reduced coenzyme (NADH2)
Result is transfer of energy (and H atoms) from fuel molecule to reduced
coenzyme
2. phosphorylation
a. transfer energy from
reduced coenzymes (NADH2) to form bond between ADP and P to form ATP
(add phosphate group)
b. Reduced coenzyme is oxidized to NAD which is recycled to oxidation/reduction
reactions.
Result is production of ATP molecules.
NOTE: One or both reactions may be in each enzymatic pathway.
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Describe
how the two above transfer reactions result in transfer of energy.
III. Carbohydrate metabolism
in cell
A. Glucose catabolism (complete
breakdown of glucose requires 4 enzymatic pathways or steps) Ultimate
goal is to produce ATP. Only ATP can be used by cell enzymes, contractile proteins
or cell membrane pumps to provide cell function.
1. Glycolysis
(performed by enzymes in cytosol) a.
Glucose
= 2 pyruvic acid +
2ATP + 2 NADH2
Restated: Glucose
(6–carbons) enters this pathway and is anerobically broken down to 2 molecules
of pyruvic acid (3–carbons), 2 molecules of ATP and 2 reduced coenzymes.
presence of ATP indicates phosphorylation reaction occurs, presence of reduced
enzymes indicates Reduction-oxidation reaction occurs in this step.
b. ATP is used by cell immediately. Reduced coenzymes diffuse into mitochondrion.
Pyruvic acid diffuses into mitochondrion.
c. Pyruvic acid fate
1) anaerobic (low or
no oxygen) --2 pyruvic acid molecules converted to 2 Lactic Acid (making solution
more acidic)
2) Aerobic (oxygen adequate)--
2 pyruvic acid molecules
s becomes substrate of next enzyme pathway
2. Production of acetyl
CoA (also known as Decarboxylation of pyruvate) (occurs in mitochondria)
a. CoA + 2 Pyruvic acid
= 2CO2 + 2 Acetyl CoA + 2 NADH2
Restated: each pyruvic acid molecule (three carbons) enters this pathway and
is broken to produce a carbon dioxide and an acetyl molecule(two carbons) .
Resulting acetyl group and combined with Coenzyme A to form 2 molecules of acetyl
CoA and 2 molecules of reduced coenzymes. presence of reduced enzymes indicates
Reduction-oxidation reaction occurs in this step.
b. Carbon dioxide diffuses out of cell. Reduced coenzymes diffuse into mitochondrion.
Acetyl CoA diffuses into mitochondrion.
3. Kreb's cycle (occurs
in mitochondria)
a.
2 acetyl CoA= 4CO2 + 6NADH2 + 2FADH2 + 2GTP
Restated: 2 acectyl CoA molecules enter this pathway and are completely broken
down forming 4 carbon dioxide molecules and a lot of reduced coenzymes. An alternative
energy molecule, called GTP, similar to ATP is also formed. presence of reduced
enzymes indicates Reduction-oxidation reaction occurs in this step.
b. Carbon dioxide diffuses out of cell. Reduced coenzymes diffuse into mitochondrion.Most
important products are lots of NADH2 + FADH2 (= reduced coenzymes)
Describe
the result of the first three steps of glucose catabolism on glucose structure-identify
which molecules now have the original atoms and in which molecule the glucose's
energy is located
4.
Electron transport system (occurs
in mitochondria) a.
O2many NADH2 + some FADH2 +ADP + P = many ATP and H20.
Restated: Oxygen and many NADH2 and FADH2 enter this step and have some hydrogen
atomsbroken off to create a concentration gradient. This gradient (transport chain)
drives the formation of ATP from ADP and a phosphate ion. Hydrogen ions
bind with oxygen to form water. The presence of ATP indicates phosphorylation
reaction occurs in this step.
b. Oxygen is required for
this (and all steps in mitochondrion) to proceed. Excessive hydrogen ions can
inhibit this and previous steps.
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List the
steps where reduced coenzymes, carbon dioxide, ATP and water are formed. Describe
what happens to the oxidized coenzymes. Identify overal ATP production in one
glucose molecule and compare this to the potential ATP produced in glycogen.
SUMMARY
Glucose + O2 =C02 + H20 + lots ATP.
Restated: In the presence of oxygen, glucose is broken down to form carbon dioxide
and water. The energy in the glucose molecule is temporarily transfered into reduced
coenzymes and then, ultimately, transfered to form ATP molecules.
Stimulated by Insulin and Thyroxine
B. Glycogenesis (forming
glycogen from glucose)
Glycogen Storage: 20% liver, 80% skeletal
Promotes lower blood sugar: Stimulated by insulin.
C. Glycogenolysis
(breaking glycogen to glucose)
Promotes higher blood sugar: Stimulated by NE/Epinephrine and glucagon
D. Gluconeogenesis
(glucose formed from fats
and amino acids to make glucose)
Promotes higher blood sugar. Stimulated by Glucagon and Cortisol
IV. Lipid metabolism
A. Lipid catabolism
pathway used when carbohydrate fuels (glucose, glycogen) are low
1. Lipolysis (breaks triglyceride to fatty acids and glycerol)
Stimulated by hGH, thyroxine, Cortisol (and NE/Epinephrine to a small degree)
2. Beta-oxidation (breaks long chain fatty acids to 2 carbon fatty acids)
1. Glycerol (3C)
= used as substitute for pyruvic acid to enter formation of acetyl CoA step (to
provide about half of energy of glucose)
2. Fatty acids (2)
=used as substitute for
acetyl group to enter Kreb's cycle ( to provide lots of energy)
If there are not enough
carbohydrates (or too much fats) then fats not be completely oxidized will form
ketones, like acetone (ketogenesis), which are acidic thereby decreasing
blood pH.
SUMMARY. Lipids are broken down to fatty acid pieces and glycerol and used
in glucose catabolism pathways to provide energy to form ATP.
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B. Lipid anabolism
Lipogenesis - excess glucose
converted to glycerol and then to form triglycerides)
Stimulated by Insulin.
V.
Protein Metabolism A.
Protein catabolism (Protein lysis)1.
Proteins broken to amino acids
Stimulated by Cortisol
2. Amino acids are deaminated (NH2 or amine is removed) and then enters Kreb's
cycle
3. amine converted to
ammonia (highly toxic)
UREA formed from
ammonia in liver. Both are secreted from kidney
SUMMARY
amino acid + O2 =C02 + H20 + lots ATP + Ammonia
Proteins are are broken down
to amion acid pieces and used in glucose catabolism pathways to provide energy
to form ATP. (
but also produce dangerous toxic ammonia).
B. Protein anabolism
(synthesis)
peptide bonds formed between
amino acids to form polypeptides
at ribosome
Stimulated by hGH and Insulin.
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Compare and
contrast carbohydrate, protein and lipid catabolism.
VI. Regulation of metabolism
A). Absorptive state (fed)
mostly anabolic and dominated
by Insulin
Lipogenesis, Glycogenesis
B). Post absorptive state
(fasting)
mostly catabolic dominated by glucagon and cortisol
Lipolysis, Glycogenolysis, Gluconeogenesis
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Identify
the hormones and processes the dominate each state.
Professor
Thomas M. Lancraft
Human Anatomy
and Physiology Courses
at St. Petersburg College
St. Petersburg/Gibbs Campus
5/2008