Amino acid structure
Zwitterionic properties of amino acids
hydrophobic, aliphatic side chains
hydrophobic, aromatic side chains
polar, neutral side chains
aromatic amino acids absorb UV light
negatively charged side chains
at physiological pH
positivly charged side chains
Histidin can accept or donate protons at physiological pH
7 of the 20 amino acids have readily (leicht) ionizable side chains
Amino acids are linked by peptide bonds to form polypeptide chains
Amino acid sequences have direction
polypeptide bond has directionality (polarity)
amino terminal = beginning of polypeptide chain
polypeptide consists of repeating part = backbone + variable part = amino acids
secondary structure: Alpha helix
essentially all alpha helices in proteins are right handed
hydrogen bonds between C=O and NH in i and i+4
side chains on beta carbon have destabilising effect
Prolin breaks the helix
secondary structure: beta strands form beta sheets
beta sheets are formed by adjacent beta-strands
polypeptide in beta-strand is fully extended
hydrogen bonds link strands in beta-sheet
tertiary structure: water-soluble proteins fold into compact structures with nonpolar cores
spatal arrengement of amino acids
amino acids that are far apart in primary structure can be neighbours
globular proteins are very compact
interior of globular proteins consists mainly of hydrophobic amino acids
exterior of globular proteins consists charged and poalr amino acids
membrane proteins have the reverse distribution of hydrophilic and hydrophobic amino acids
tertiary structures: motifs and domains
motifs (secondary structures) are combinations of secondary structures that are found in many proteins
some proteins have two or more identical or similar compact structures called domains
quarternary structure: complex assemblies from subunits
many proteins are composed of multiple polypeptide chains (subunits)
Quarternary structure can be as simple as two identical polypeptide chains or ascomplex as dozen of different polypeptide chains
Life cycle of a protein - cellular proteostaisis
The amino acid sequence of a protein determines its 3D structure
proteins dont fold by trying all possible conformations
real folding time is 1s
Protein folding
proteins fold spontaneously
native and refolded protein have identical properties
folding information is coded in sequence
nucleation-condenstation model: progressive stabilisation of folding intermediates
some proteins need help folding
-> generally requires ATP
Protein targeting: Compartimentalisation creates transport problems
signal sequences are necessary and sufficient for protein targeting
organelle specific receptors or soluble targeting factors
Protein conducting channels formed by integral membrane proteins
driving force for ranslation
molecular chaperons
protein degradation
peptide bond cleavage is exergonic
proteases are not ATP dependent
catalytic mechanism:
transfer of protons
nucleophilic attack on the carbonyl-C atom of the peptide substrate
covalent intermediate or not (depends on class)
Metabolic pathways: Glycolysis and Krebs Cycle
3 steps of energy extraction
digestion, Production of acetyl-CoA, complete oxidation of acetyl-group to CO2
Catabolism and anabolism
Phototrophic organisms: get energy from sunlight
Chemotrophic organisms: get energy through oxidation of nutrients
energy carrier: ATP, NADH, NADPH, FADH2
Thermodynamic principles in metabolism
Gibbs free energy is determined by concentration of reaction partners
deltaG kleiner 0 -> exergonic
deltaG größer 0 -> endergonic
What happens in equilibrium
deltG=0+
Universal energy and electron carriers
ATP/ADP
high posphorylation potential of ATP is achieved by
resonance stabilization
electrostatic repulsion of the 4 negative charges at ATP
stabilisation through hydration of ADP and Pi
gain in entropy
carriers molecules in metabolism
carriers are kinetically very stable
exchange of activated groups is carried out by a small set of carrier molecules (economical and elegant)
based on watersoluble vitamins
FADH, FMN -> Vitamin B (Riboflavin)
NADH, NADPH -> Vitamin B3 (Niacin)
Coenzym A -> B5 (Pantothenate)
NAD+/NADH in catabolic processes
NADP+/NADPH+ in anabilic processes
ATP, NADH, CoA, FAD all contain an ADP
Glycolysis overview
Glycolysis steps and Thermodynamic
open system equilibrium
hexokinase, phosphofructokinase and pyruvate kinase
speed-determining steps
pacemaker reactions
flow of intermediates is constant in steady state
synthesis and degradation are in balance
Gluconeogenesis takes place in liver
formation of glucose from non carbonhydrates via pyruvate to keep blood sugar levels constant
relevant during hunger
can not produce glucose from acetyl-co
exergonic reactions are bypassed
3 cell compartments: cytosol, mitochondria, ER
costs more energy than glycolysis
Glycolysis/Glyconeogenesis overview
Pyruvate and than?
Pyruvate needs to be further processed to generate NAD+ and maintain redox balance
Pentose phosphate pathway
takes place in all cells
supplies riboses for DNA and RNA
delivers NADPH/H+
tasks of NADH and NADPH
NADH
used to produce ATP in the respiratory chain
is predominantly oxidized as needed in Glycolysis
NADPH
for reductive biosynthesis
protects the erythrocyte membrane and liver cells from dell toxins
preferably present in the reduced form
Acetyl-CoA interface of ATP generation
Acetyl-CoA
smallest common product of degradation of amino acids, fatty acids and carbohydrates
takes C2-molecules into Krebs cycle
produced in mitochondrium
Pyruvate-dehydrogenase complex
localised in the mitochondiral matrix
catalysis the oxidative decarboxylation of pyruvate to acetyl CoA
is a multi enzyme complex
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