Zellbiologie

Metabolism (1) : Glycolysis and fermentation/respiration Metabolism (2) : Lipid metabolism / Amino acids metabolism Introduction to immunology

Metabolism (1) : Glycolysis and fermentation/respiration Metabolism (2) : Lipid metabolism / Amino acids metabolism Introduction to immunology


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Metabolism

Metabolism (from Greek: μεταβολή metabolē, "change") is the set of life-sustaining chemical transformations within the cells of living organisms.

Metabolism is a combination of breaking large molecules into bricks and rebuild large molecules with those bricks, that consumes energy, and/or produces some

anabolism

Precursors (e.g. glucose, amino acids, fatty acids, bases) are “transformed” into complex molecules
(e.g. carbohydrates, proteins, lipids, DNA, RNA) by using the energy received from catabolism.

catabolism

Catabolism (from Greek κάτω kato, "downward" and βάλλειν ballein, "to throw") is the set of metabolic pathways that breaks down molecules into smaller units that are either oxidized to release energy

Energy units

Kilocalorie: (kcal or Cal) is 1000 cal or the amount of energy to elevate the temperature of 1 kg of water of 1°C

KiloJoule: (kJ) is roughly 4.2 kcal

bond energy

princip of catabolism

oxydation of high energy bond to low ones

enery in food

energy transfer

ATP ADP

phosphoanhydride bonds
Water can be added to ATP to form ADP
Delta G0 = -30.5KJ/mol
 

ATP reaction coupling

Proton carriers

  • > Important carrier molecules
  • > Oxydation/reduction reaction require protons/electrons
  • > Proton carriers accept temporarily protons (H + ) and high energy electrons (e - )
  • > NADPH, NAD+ and FAD

Energetically unfavourable reactions

Energetically unfavourable reactions (ΔG > 0 edergonic) can only occur if they are coupled to an
energetically favourable (exergonic) reaction and the net free-energy change for the pair of coupled reactions
is less than zero.

Digestion of the most important nutrients

  • Carbohydrates: Starch is hydrolysed by α-amylase (produced by pancreas) to disaccharides. The disaccharides are hydrolysed to monosaccharaides which can be absorbed from the intestine
  • Lipids: Must be emulgated by bile from the liver. Then they are hydrolysed by lipases to fatty acids and glycerol and taken up into the cells
  • Proteins: Are first denatured in the stomach by acids and shaking. In the next steps they are hydrolysed to polypeptides by pepsin and t

Biological oxidation: carbohydrates

Glycolysis

The glycolysis can be divided into three parts:

  • In the first step, energy (2 ATP) is invested to make one molecule of fructose 1,6-biphosphat out of one molecule of glucose
  • In the second step, the six-carbon sugar is cleaved to two molecules of glyceraldehyde-3-phosphate (three-carbon-sugars)
  • In third step, energy is generated (4 ATP) by making two pyruvate molecules out of the two glyceraldehyde-3-phosphates.

Alternative glycolysis

lactate is release in blood and reach the liver. There the lactate is re-cycle in pyruvate that can be retransformed into glucose

Formation of (activated) acetic acid (in mitochondria)

 

  • A carbon is cleaved from the pyruvate to form acetic acid. The cleaved carbon is released as CO 2 .
  • Activation of acetic acid with CoA (a derivative of pantothenic acid = vitamin B 5 ) to form acetyl-CoA
  • Formation of NADH+H+

--> This processes are all done by one multienzyme complex called pyruvate dehydrogenase

TCA-Cycle (Krebs-Cycle, Citrat-Cycle --> in mitochondria):

E4&4)+1&7#7.34&4).&
E4&4)+1&7#7.34&4).&
 

  • Degradation of (activated) acetic acid to CO2 and H2 (in form of NADH or FADH 2 )
  • Transfer of the bound H2 to respiratory chain

--> It is the link between glycolysis and respiratory chain and the metabolic link between metabolism of carbohydrates, lipids and amino acids

Respiratory Chain (inner mitochondrial membrane):

  • NADH gives two electrons to the first complex (NADH dehydrogenase complex) of the respiratory chain: NADH --> NAD+ + H+ + 2e- , the H+ remain in the matrix of the mitochondrion
  • The electrons are passed on through the different complexes of the respiratory chain, going to a lower level energy each time they “pass” a complex. The energy from the electrons is used by the complexes to transfer H+ form the matrix to the intermembrane space of the mitochondrion against the concentration gradient
  • At the end of the electron transport chain, the electrons from, together with the H+ which remain in the matrix and with 1⁄2 O2 , H2O
  • The H+ which are in the intermembrane space can flow along their concentration gradient back into the matrix through a transmembrane protein called ATP synthase which uses the energy of the H+ flow to produce ATP from ADP.
  • ATP synthase can also transport H+ against the concentration gradient from the matrix to the intermembrane space (energy provided by the break down from ADP to ATP)

Glycogenin

An enzyme involved in converting glucose to glycogen. It acts as a primer, by polymerizing the first
few glucose molecules, after which other enzymes take over. Thus it is found in the middle of a glycogen
molecule.

glucose storage

liver 150g
muscle 250g

energy regulation

pancreas secrete insulin in case of high glucose concentration in blood
pancreas secrete glucagon in case of low glucose concentration in blood

main component of bile acid

cholesterol from fat

Fat Digestion

Triglycerides a cleaved hydrolytically (step-by-step) by lipases. The result is one molecule of glycerol and three
free fatty acids. The glycerol is channelled into glycolysis. The fatty acids are not soluble in water but can be
emulsified by bile acids such as cholic acids (derived from cholesterol) and their conjugated bile acids
gylocholic acid and taurocholic acid. The “output” of this process are mixed micelles of about 5nm diameter
which consist of bile salt on the outside and cholesterol and the free fatty acids on the inside. These micelles
can now be taken up by the intestine. Once in the body, the fatty acids are processed further on.

Chylomicrons

They transport dietary lipids from
the intestines to other locations in
the body. Chylomicrons are one of
the five major groups of lipoproteins

Fat Digestion and Utilisation

The fatty acids are, as described above, hydrolysed by lipases. In a next step, the fatty acids are activated in
order to produce Acyl-CoA by transferring the fatty acids to CoA. The acyl is cleaved again from CoA and added
to carnitine. The Acyl-Carnitine complex is transported into the mitochondrion. There, the complex is cleaved
again, the carnitin leaves the mitochondrion again and the acyl is once again bound to CoA. In the β-oxidation
process itself, the Acyl-CoA is (in several steps) “cleaved” in an Acetyl-CoA, which is transferred to the TCA-
cycle and another Acyl-CoA (Acly is now shorter by 2 C-atoms).

proteasome

Das Proteasom (auch: Macropain) ist ein Proteinkomplex von 1700 kDa, der im Cytoplasma und bei Eukaryoten auch im Zellkern Proteine zu Fragmenten abbaut und daher zu den Peptidasen (auch Proteasen) zählt.

Eucaryotic Cells
> ATP-dependent
> > Proteins are first „marked“ Ubiquitin
> very conserved mechanism
> Degradation by a very large cytosolic Enzyme complex = Proteasome

amino acid catabolism

fat digestion easy

  1. digestion -->micelle (with bile acid (cholesterol))
  2. activatein cytosol-->acyl-CoA
  3. transport mitochondria
  4. Beta-oxidation-->acetyl-CoA
  5. TCA-cycle -->NADH etc
  6. oxidative phosphorylation-->ATP
     

lysosome

protein cycle

Since synthesis and degradation of body proteins (total about 10 kg) takes place all the time and there is also a
continuous excretion and uptake of proteins , there are about 70 to 100 g of free amino acids in our body at
any given time.

Proteolysis:

Proteolysis: Hydrolysis of the peptide bonds between amino acids.

There are several reasons why proteins are degraded:

  • Digestion (gastrointestinal tract): Enables absorption of amino acids, provide amino acids for protein biosynthesis or as sources of energy
  • Quality control: “aging”/damaged proteins or newly synthesised proteins with defects
  • Regulation of biologically processes such as cell cycle, signal pathways (receptors and their ligands) and tissue remodelling

--> Proteins are typically degraded by lysosomes but there is also a lysosomal-independent degradation, which is ATP-dependant

Two part in the immune system
 

Two part in the immune system
— Innate immunity
— Adaptive immunity

Immunity starts by a physical barrier
 

Immunity starts by a physical barrier
— skin
— respiratory tracts
— digestive tracts

Self Vs Nonself

> Once inside, pathogens are recognized as “foreign” molecules
> Immune system is constantly “scanning” the inner environment for organism that are not produced by the body
> Immune cells interact with other cells by cell-cell contact
> “Self” molecules induce a neutral reaction when “nonself” induce an activation

pathogen detection

 

  • Foreign or Non-self molecules are recognized by receptors
  • Pattern recognition receptor (PRR)
  • Main family: Toll-like receptors (TLR)
  • Recognize broadly shared pathogen molecules (PAMPs)
  • it is a “super” protein family

Toll-like receptors (TLR)

  • TLR-1:- Bacterial lipoprotein
  • TLR-2:- Bacterial peptidoglycans
  • TLR-3:- Double stranded RNA
  • TLR-4:- Lipopolysaccharides
  • TLR-5:- Bacterial flagella
  • TLR-6:- Bacterial lipoprotein
  • TLR-7:- Single stranded DNA

Polymorphonuclear leukocytes

  • White blood cells (leukocytes)
  • 3 types: Neutrophils (60%) Eosinophil (5%) Basophil (<0.5%)
  • First line of active defense
  • Respond to foreign molecule recognition by degranulation or phagocytosis

neutrophils

  • Very aggressive cells
  • Short life span (around 5 days)
  • Attack pathogen by phagocytose
  • granules contain anti-bacterial agents

— defensins (make pores in bacterial membranes)
— proteolytic enzymes (e.g. Cathepsin G)
— lysozyme (enzyme digesting the bacterial wall)

  • Remain at the infection site and are degraded by macrophages or excreted in pus.