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Lecture notes of 51 pages for the course human and animal physiology at WUR (whole bag.)

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HUMAND AND ANIMAL PHYSIOLOGY
1.2- Energy metabolism and thermoregulation
Two critical concepts drive the control of energy metabolism:

1. Because food intake is intermittent, the body must store nutrients during periods of intake and then
break down these stores during period between meals.
2. Because the brain depends on glucose as its primary energy source, blood glucose levels must be
maintained at all times even between meals.

anabolism: using the same small biomolecules that provide energy, to synthesize larger biomolecules.

When energy is released in a reaction it must be ‘captured’ in certain forms before it can be used to do work,
otherwise it is simply released as heat into the environment.

• Energy metabolism: all chemical reactions in the body which are involved in energy storage and usage.
- Catabolism: break down and energy producing
- Anabolism: building and energy storage

Regulation of metabolic pathways:

Controlled by anabolic, catabolic and compartmentations.

ATP – adenosine triphosphate

Is a universal energy carrier that captures fee energy by catabolism of
macro nutrients, which is needed for labor of storage → ATP is
synthesized from the nucleotide adenosine diphosphate and a
phosphate: ADP + Pi + energy → ATP (+ H2O), so a condensation
reaction, in order to make one mole of ATP you 7kcal.
The formation of ATP is a phosphorylation reaction, because of the addition of a phosphate group. ATP
synthesis occurs through 2 processes:

1. Substrate- level phosphorylation; a phosphate is transferred from a metabolic intermediate to ADP, to
form ATP; X - P + ADP → X + ATP
2. Oxidative phosphorylation; ADP binds with a free inorganic phosphate to form ATP: ADP + P →ATP,
requires the electron transport system in mitochondria and oxygen

Loss of ATP is called hydrolysis because water is a reactant: ATP (+ H2O) → ADP + Pi + energy
Because ATP hydrolysis releases energy and involves the splitting of a single bond—the bond between ATP and
one of the phosphate groups—that bond is commonly termed a high-energy phosphate bond.

• Aerobic
- C6H12O6 + 6 O2 + 32 ADP + 32 Pi → 6 CO2 + 6 H2O + 32 ATP
- Released energy during glucose oxidation = 686 kcal
- Energy storage of 1 ATP molecule is 7 kcal
- Efficiency ATP production is 32,7%
• Anaerobic
- Low oxygen so no O2 available as an electron acceptor
- No activity of krebs cycle and ox-phos
- Accumulation of pyruvate and NADH → shutdown glycolysis
- Glucose oxidation: Pyruvate → lactate : 2 ATP + 2 NAD+
- Cori cycle: liver converts lactate into glucose
- Efficiency ATP production Is 2 %

ATP is built from the base adenosine, a ribose and triphosphate groups.
ATP synthesis involves a positive energy change and thus does not occur spontaneously.

, HUMAND AND ANIMAL PHYSIOLOGY
ATP is released by catabolism, also glucose
oxidation:

1. Glycolysis in cytosol
2. Krebs cycle (TCA) in mitochondrial matrix
3. Oxidative phosphorylation in inner
mitochondrial membrane

Glycolysis: splitting of sugar by a metabolic pathway.

- At the end of glycolysis each glucose has been split into 2 molecules of pyruvate
- During this process, 2 ATP molecules are consumed (step 1 &3). 4 ATP is produced by the substrate-
level phosphorylation (2 in step 7 and 2 in 10), which gives a net synthesis of 2 ATP for each
molecule glucose consumed.
- 2 molecules of NAD+ are reduced in step 6, yielding 2 molecules of NADH for every glucose
molecule.

Overall: glucose + 2 NAD+ + 2 ADP + 2 Pi → 2 pyruvate + 2 NADH + 2 H+ + 2 ATP

C6H12O6 + 6 O2 → 6 CO2 + 6 H2O + energy - released energy per mole glucose is 686 kcal.
Cells are able to synthesize ATP using energy from glucose oxidation because it has a negative energy change,
and therefore occurs spontaneously. The oxidation of one mole of glucose releases enough energy to make 98
moles of ATP, but the actual used amount is 38 moles of glucose → C6H12O6 + 6 O2 + 38 ADP + 38 Pi → 6 CO2
+ 6 H2O + 38 ATP. Little explanation: 38n x 7kcal/mole= 266 kcal, then -686 kcal + 266 kcal = -420 kcal, since
the net energy is negative the reaction can proceed in a forward reaction to yielding ATP.

The Krebs cycle: circular.
after glycolysis where pyruvate enter the mitochondrial matrix, it
is converted into acetyl CoA in a reaction that reduces NAD+ to
NADH + H+ and produces a CO2- linking step since Acetyl CoA is
the initial substrate for the Krebs cycle = 2 pyruvate + 2 CoA + 2
NAD+ + 2 H2O → 2 acetyl CoA + 2 NADH + 2 H+ + 2 CO2

- End of the turn in the Krebs cycle a total of 2 CO2
been generated as end products (step 3-4)
- Only 1 ATP is generated directly by substrate- level
phosphorylation (step 5)
- In a single turn of the cycle, total 4 reduced
coenzymes- 3 NADH + H+ and 1 FADH2 are
produced (step 3,4,6 and 8)
- Final product is oxaloacetate, which reacts with
acetyl CoA to start the cycle again.

Overall: acetyl CoA + 3 NAD+ + FAD + ADP + Pi + 3 H2O S 2 CO2 +
3 NADH + 3 H+ + FADH2 + ATP

Oxidative phosphorylation: most ATP made in cells

- NADH and FADH2 release electrons and protons to
the ETC and return NAD+ and FAD
- Released electrons move through the chain, the energy is used to transport H+ across inner
mitochondrial membrane – stores energy
- stored energy is released when hydrogen ions flow through ATP synthase, which uses the energy to
make ATP → 3 ATP from NADH and 2 ATP from FADH2
- The released electrons and protons come together again in the mitochondrial matrix to form water
as an end-product.

, HUMAND AND ANIMAL PHYSIOLOGY
The transport in the inner mitochondrial membrane of hydrogen atoms or electrons which release energy –
using an electron transport chain
Electrons are carried to the electron transport chain by reduced coenzymes (NADH and FADH2) from
glycolysis, the linking step, and the Krebs cycle. These reduced coenzymes then release their electrons to the
chain that functions as electron acceptors. These electron acceptors donate their electrons to other electron
acceptors, which pass them on to other acceptor. Each time electrons move from one component to the next,
they lose some energy—energy that is used in making ATP.

The harnessing of this energy to make ATP, which is carried out by a mechanism; chemiosmotic coupling
Couples electron transport to ATP synthesis, known as chemiosmotic coupling; first uses the energy released
in the electron transport chain to transport hydrogen ions across the inner mitochondrial membrane against
their concentration gradient, and then uses the energy stored in this gradient to make ATP.

Overall: 10 NADH + 10 H+ + 2 FADH2 + 34 ADP + 34 Pi + 6 O2 → 10 NAD+ + 2 FAD + 12 H2O + 34 ATP

- Any drop in NAD+ levels in a cell is a potential threat to all
ATP production because a supply of NAD+ is necessary for
proper operation of both the glycolysis pathway and the
Krebs cycle → this threat can be prevented because most
cells contain lactate dehydrogenase (LDH), which converts
pyruvate to lactate; pyruvate + NADH + H+ →LDH→ lactate +
NAD+
- Because lactate is potentially harmful to cells, they must get
rid of it. When oxygen availability to a cell returns to normal,
pyruvate begins to proceed to the Krebs cycle as it usually
does, and the concentration of pyruvate in cells decreases.
- Cori cycle: Most of the lactate is produced in muscle cells,
transported by the blood to the liver, converted to glucose,
and then transported in blood back to muscle cells.

Metabolism of macronutrients
Glycogen: through glucose

1. Uptake: glucose transporters
2. Used for energy
3. Metabolized via other routes;
glycerol, fatty acids, nucleotides
4. Storage; forming & storing
glycogen (glycogenesis) mainly
muscle, liver and brain
5. Glycogen broken down into
glucose for energy (glycogenolysis) - When glycogen is
broken down, glucose-6- phosphate, an intermediate
of glycolysis

Gluconeogenesis: formation of new glucose mainly carried
out in the liver since it needs all enzymes to run glycolysis in
reverse, 3 ways:

1. Glycerol → glycerol phosphate → glycolysis in reverse
2. Lactate → pyruvate → glycolysis in reverse
3. Amino acids →pyruvate after entering Krebs cycle→ oxaloacetate → phosphoenolpyruvate →
glycolysis in reverse

, HUMAND AND ANIMAL PHYSIOLOGY
Fats: through triglycerides
In adipose tissue storage depot for fats
Triglycerides broken down (lipolysis) Is the first stage of fat breakdown, where
fatty acids separate from the glycerol.

1. Lipoproteins in blood are broken down to free fatty acids and
monoglycerol (lipoproteins lipase)
2. Uptake: diffusion into cell
3. Used: fatty acids broken down into acetyl CoA ( Beta- oxidation in
mitochondrial matrix) and oxidized
4. Storage: fatty acids and glycerol assembled into triglycerides
(lipogenesis; fats from other nutrients)



Proteins: through amino acids

1. Uptake: specialized transporters
2. Storage: assembled to proteins in muscle
3. Used: deamination NH3
4. Proteins degraded to amino acids (proteolysis) if
necessary, those AC are deaminated where3 NH2
is removed and ammonia NH3 forms.

Note! Proteins always have a functional role!

An essential nutrient is any biomolecule necessary
for proper body function that cannot be
synthesized in cells and, therefore, must be obtained from dietary sources.




Energy balance

Blood flow distributes these nutrients to tissues where cells take them up, these molecules undergo possible
one of the 3 fates:

1. Biomolecules can be broken down into smaller molecules in which energy is released, that can be used
for cellular processes.
2. Biomolecules can be used as substrates to synthesize other molecules needed by cells and tissues for
normal function, growth and repair
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