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METABOLISM - All chemical reactions

- Metabolic pathways are highly regulated


that occur in living organisms, including
digestion and the transport of substances Rate-Limiting enzyme/committed
into and between different cells.
enzyme
- Avoids futile cycling by regulation of
Enzyme-catalyzed reactions
metabolic pathways
- Allow organisms to grow and reproduce, - Usually (not always) the primary
maintain their structures, and respond to enzyme,
their environments.
- Catalyzes the first irreversible reaction
- To extract energy from nutrients or solar in a metabolic pathway
energy
Irreversible step
- To synthesize the building blocks that
- Spontaneous reaction, which requires a
make up the large molecules of life:
big (delta G)
proteins, fats, carbohydrates, nucleic
- Enzyme, which catalyzes the forward
acids, and combinations of these
reaction, cannot catalyze the reverse
substances;
reaction
- An enzyme can be used to catalyze a
Principles of Metabolism
reaction that produces an intermediate
- Fuels are degraded and large
from a substrate. That same enzyme
molecules are constructed in a series of cannot be used to return the intermediate
linked reactions
into its substrate
- ATP links energy-releasing pathways
with energy requiring pathways
Metabolic Pathways in the cells
Catabolism breakdown; produces
always require a series of enzymatic
energy
reactions. It cannot happen if theres only
Anabolism synthesis; build-up; makes 1 enzyme or 1 reaction involved; 1
use of energy
enzyme should always precede the next

enzyme.
Michaelis-Menten Constant (Km)
will determine which enzyme is going to
bind to a substrate;
responsible for the specificity of enzymes
LOW KM, HIGH AFFINITY
FAT - The primary form of potential
chemical energy is stored in the body
C. Energy Metabolism
BMR (Basal Metabolic Rate)
- Amt of energy needed by the whole
body during a resting state (sleeping)
- Necessary amount to keep vital organs
working (heart, hrain, kidneys, blood)
Varies according to mental/physical
activity, sex, age
- Measured in terms of calories
- Calorie requirement that a person will
utilize depends on the nutrients which are
oxidized through metabolic pathways
1. Metabolic Fuels & their Pathways
GLYCOLYSIS CHO and some AA
PYRUVATE OXIDATION Some AA
CITRIC ACID CYCLE Fatty acids, AA
=OXIDATIVE PHOSPHORYLATION

CARBOHYDATES
- Main source of energy; first line of
macronutrients that the cells are going to
utilize
- Glycogen (Storage form of
polysaccharides in animals) only found in
2 organs (liver and muscle)

LIPIDS
16C saturated fatty acid, Palmitic Acid
- Most common fatty acid in the body is a
- More triglycerides can be stored in
obese individuals due to expansion of
adipose cells

PROTEINS
- not considered storage forms of amino
acids (Their principal function is not to
provide energy but to provide structure)

ATP & Phosphorylation


ATP (Adenosine Triphosphate)
- Cellular form of energy
- Has phosphoanhydride bonds, which
makes it capable of supplying energy for
cellular activities
- Phosphate group attached to carbon 5,
other phosphate groups bind to each
other through phosphoanhhydride bonds
- Energy is specifically derived from the
hydrolysis of the phosphoanhydride
bonds
- ATP can never be stored- 100g in blood
ATP is continually synthesized
ATP -> ADP + Pi (inorganic phosphate)
ATP -> AMP + Pp (pyrophosphate)
Resting state : 40 kg of ATP daily
Strenuous exercise: 0.5 kgs/min of ATP
PHOSPHORYLATION
ATP Production process
- ADP is the substrate, PO4 is added

acceptor
Tissue Specific Metabolism
Brain
- Dependent on glucose for energy
- Neurons are continuously firing; need
for glucose is high; adequate supply is
needed; amount of glucose is dependent
on how often we eat
Small intestine
- Site of absorption of monosaccharides
(Glucose, Galactose, Fructose).
- Travels to liver through portal circulation
b. Oxidative Phosphorylation
- Glucose crosses the small intestine
- Occurs in the mitochondria
through transporters SGLT1, GLUT 5,
- Transfer of high energy phosphate
and GLUT2
group requires the presence of electrons; Fatty acids and cholesterol
electrons will enter mitochondria via
transported from the small intestines with
proton pump
the use of lipoproteins (Chylomicrons) by
- In the process, the proton pump will
means of lymph circulation
allow for the ATP synthase to attach the Pancreas- Regulates energy-related
high energy phosphate bonds to
metabolic activities
regenerate ATP
- Secretes insulin (fed state) and
- Not substrate, but movement of
Glucagon (starved state)
electrons that will propel ATP
Insulin allows transport of glucose to
generation
insulin- dependent organs
- No involvement of intermediate, but
Glucagon mobilizes the glucose in the
oxygen is the final hydrogen/electron
liver for it to be able to provide the
a. Substrate - Level Phosphorylation
- Occurs in the cytosol
- Need of substrates/ intermediate
- Enzyme has ability to capture/harvest
inorganic phosphate from cytosol and
attach it to ADP, coupled with an
intermediate PEP Phosphoenolpyruvate
that will be converted into pyruvate (ATP
and pyruvate are formed using same
enzyme, therefore, substrate - level)

necessary ATP source for the brain


Liver Metabolic Hub
- Distributes the different nutrients to the
different organs

Principles of Energy Metabolism


Energy metabolism relates energy input
in the whole organism to energy
expenditure; positive and negative
Brain: transports ions to maintain
energy balance
membrane potential; integrates inputs
- There should be a balance between
form body and surroundings sends
intake and expenditure.
signals to other organs
If intake > expenditure, balance is tilted to
Lymphatic System: Carries lipids from
more storage than usage and can lead to
intestines to liver
obesity or metabolic syndrome
Adipose Tissue: Synthesizes, stores, and - Carbon in fuel molecules is oxidized to
mobilizes triacyl glycerols
CO2 to regenerate ATP from ADP and Pi
Skeletal Muscle: Uses ATP to do work
Small Intestine: Absorbs nutrients from
HIGH Energy content in metabolic fuels
the diet, moves them into the blood or
HIGH Amt of energy expended through
into the lymphatic system
endergonic reactions
Portal Vein: Carries nutrients from
intestine to liver
Acetyl CoA - substrate for Krebs Cycle
Liver: Processes fats, CHO, CHON from Krebs Cycle - produce electrons that are
diet; synthesizes and distributes lipids,
transported by NAD and FAD so that they
ketone bodies and glucose for tissues.
will be able to enter the oxidative
Converts excess Nitrogen to Urea
pathway in Electron Transport Chain;
Pancreas: Secretes insulin and glucagon common pathway
in response to change to glucose conc.
- Metabolic pathways are irreversible
- Every MP has a first committed step

- All metabolic pathways are regulated


OXIDATION REDUCTION REACTION
- Involves the loss or gain of electrons
- Use of coenzymes NADH and FADH2
- Transfer one or two electrons
- Terminal electron acceptors for different
organisms (O2, NO3-, Fe3+)
Stage 1 - macromolecules are broken
down to monomeric units
Stage 2 - monomeric units undergo
oxidation to produce a common product,
which is Acetyl CoA
Stage 3 - oxidative phosphorylation electrons from Krebs cycle produce ATP;
occurs in mitochondria; produces the
most ATP compared to other pathways;
final acceptor is water

REGULATION OF METABOLISM
- Utilization of metabolic fuels by different
organs in the human body is controlled at
the cellular level as a function of nutrient
availability
Allosteric Modulation
- Allosteric effectors bring about catalytic
modification by binding to the enzyme at
distinct allosteric sites.
- The hallmark of effectors is that when
they bind to enzymes, they alter the
catalytic properties of an enzyme's active
site.
- Vmax can be increased or decreased,
or the Km can be raised or lowered
Covalent Modification
- Addition of or removal of phosphate or
adenylate - Protein kinase
- Use of ATP

Gene expression
- Important regulatory mechanism of
enzymes
- Longest to happen; nucleus needs to
express the gene, transcribe to mRna,
and mRna to ribosome
Endocrine Secretions
- Hormones, hypothalamic hormones,
adipose tissues (produces adiponectin,
lectin)
Amount of Enzymes
- Dependent on rate of synthesis/
degradation
Accessibility of Substrates
- Compartmentalization/ controlling flux of
substrates

Metabolism at Different States


1. Fed State
- Organs are active
- Consumption of food leads to dietary
supply; nutrients will enter the liver; the
liver distributes

2. Overnight Fast
- Liver will still send glucose to the brain
but it's coming from glycogen
- Glucose does not come from dietary
supply

3. Starved State - Prolonged starvation glucose still being produced; coming from
carbon skeleton of amino acids; amino
acids have carbon chains and will be
dependent on the side chain of amino
acid
- Ammonia production; toxic, will cross
blood brain barrier and damage neurons;
converted to urea, a non toxic form
- BUN and creatinine are measured in
blood
Ketone bodies (from degradation of
amino acids) - by products in prolonged
starvation