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Intro to Biomolecules:
Evolutionary Timeline:
Energy Charge:
Salivary Buffering:
pH = -log[H+]
Each increase in 1 unit of pH is 10-fold difference in H+ concentration
Henderson Hasselbalch:
Amino Acid:
o Arginine
Hydrogen Bond can be formed by:
o Ser
o Thr
o Asn
o Gln
Cysteine forms disulfide bonds
Amino acids and glucose are transported together with Na+ (from lumen to blood)
o Ex: Na+/Lysine Symporter (2 Na+ in, 1 Lys in)
Zwitterionic:
o Acidic Amino Acids: have +1 charge
o Basic Amino Acids: have -1 charge
Phosphorylation can be done with OH side groups:
o Tyrosin
o Serine
o Threonine
Lysine can be acetylated or methylated
Glutamate can have a carboxyl group added to help blood glotting
N-terminals of amino acids can be acetylated
Histone proteins have modified histamine that was acetylated
Primary (sequence)
o Linear arrangement of AA
Secondary (local folding):
o Alpha helix: stabilized by H bonds
o Beta sheets:
Held by H bonds
Parallel or antiparallel
o Motifs:
EF Hand
Zinc Finger (part helix part pleated sheet)
Tertiary (overall conformation)
o Hydrophobic interactions
o Difsulfide Bridges
o H-bond
o Electrostatic interactions
Quaternary (multimeric structure)
o Ionic bond
o Hydrogen bond
o Hydrophobic (va der waals)
-turn:
Enzyme Catalysis:
Enzyme Nomenclature:
o Oxidoreductases: oxidation-reduction reactions
o Transferases: transfers C, N, or P groups
o Hydrolases: cleavage by addition of water
o Lyases: cleaves of C-C
o Isomerases: forms isomer
o Ligases: forms bond between carbon and another compound (CO2 added to pyruvate)
Coenzymes:
o Apoenzymes: inactive
o Holoenzyme: active
Cofactors: metal ions
Equilibrium constant: [product]/[reactant]
Exergonic: energy releasing
Endergonic: energy absorbing
Delta G = negative spontaneous reaction
Delta G conditions:
o 298K
o 1 atm
o pH 7.0
o Initial concentrations of 1M for all reactants and products
Reaction rate increases linearly with temperature until certain point, then decreases
Substrate binding in active site of trypsin-like serine proteases:
o Catalytic triad: ASP-102, HIS-57, SER-195
o HIS-57 deprotonates deprotonates serine
o Hydroxyl group of series mediates catalysis
o Oxygen from serine attacks peptide bond
o Aspartic Acid stabilizes peptide with negative carboxyl group
o Water comes in and hydrolyzes peptide bond
o *Specific site is only for Lysine or Arginine
Enzyme Kinetics:
Michaelis-Menton:
Glycolysis:
10 reactions
Aerobic: pyruvate acetyl CoA
Anaerobic lactic acid
Insulin regulates GLUT4, which takes in glucose to adipose/muscle
1 oxidative step where NAD becomes NADH
o G3P oxidized to 1,3-BPG
Hexokinase:
o Primary enzyme for first step
o High affinity for glucose
o In Liver/pancrease, glucokinase has high Km (low affinity)
Rate Limiting Steps:
o 3 reactions involving
Hexokinase
PFK (most important)
Inhibitors: ATP, citrate
Activators: AMP, F 2,6-BP
Pyruvate Kinase: activated by F 1,6-BP
Net ATP: 2
Pasteur Effect: inhibition of glycolysis by oxygen
o Rate of glycolysis greater in anaerobic than aerobic conditions
Warburg Effect: cancer cells have high rates of glycolysis and decreased Pasteur Effect
Anaerobic Conditions:
Gluconeogenesis:
Diabetes:
o Type 1: low levels of insulin
o Type II: resistant to insulin
o Starvation increased gluconeogenesis increased glucose
Insulin cannot stop this
o Muscle/adipose insulin dependent
o Insulin:
Stimulates glycolysis
Released after meal
Receptor: tyrosine kinase receptor
o Glucagon:
Inhibits glycolysis
Released in starvation
Receptor: G-protein coupled receptor
o Both Insulin and Glucagon act on:
Glucokinase
Phosphofructokinase
Pyruvate Kinase
Enzyme levels often elevated in plasma levels after damage to tissues
Markers of Liver Disease:
o Alanine Aminotransferase (ALT)
o Aspartate Aminotransferase (AST)
o Increased Bilirubin = liver disease
Markers of Heart Disease:
o Creatine Kinase Isozyme: rise after myocardial infarction
o Isozyme can be placed in electrophoresis:
Isozyme has 2 forms: muscle and brain
2 b subunits and 2 m subunits
o Both
Creatine Kinase MB and Cardiac Troponin are
increased in plasma after myocardial infarction
Metabolic Compartmentalization:
Malate-Aspartate Shuttle
Redox Couple: Malate and Oxaloacetate (does redox with
NADH/NAD)
ATP
NADH
FADH2
GTP
CO2
Glycolysis
2
2
-
Total
2
10
2
2
6
Oxidative Phosphorylation:
H+
o Complex 1: Rotenone
o Complex III: Antimycin A
Complex 1 + 2 are reduced (upstream)
Complex c + 3 + 4 are oxidized (downstream)
o Complex IV: Carbon Monoxide + Cyanide
o Complex V (ATP synthase): Oligomycin
o ATP/ADP Translocase (antiporter): Atractyloside
Uncouplers of Oxidative Phosphorylation:
o Dissipates proton gradient across inner membrane to prevent ATP synthesis
Protons are still moved into matrix by uncoupler protein NOT ATP synthetase
o BUT permits electron transport
o Energy is released as heat
o Ex:
2,4-DNP
Uncoupling Protein 1 (thermogenin) seen in brown adipose in babies
Diseases in Cell Respiration and Oxidative Phosphorylation:
o Result in Lactic Acidosis, Muscle and Nerve Pathology
o Ex:
Lebers Heriditary Optic Neuropathy
Defect in mitochondrial gene
Maternal inheritance
Blindness in teens and 20s
Optic Nerve affected
Leigh Syndrome:
Muscle and neurological problems
Lactic acidosis
Anaerobic conditions predominate thus lactic acid will accumulate
3 Lipids:
o Cholesteryl ester (CE) cholesterol
o Phosphatidylcholine (phospholipid PL) Glycerlphophocholine
o Triacylglycerol (TAG) 1-Monoacylglycerol
Glycocholic Acid:
o Bile salt (derivative of cholesterol)
o Cholic acid conjugated to glycine
Acetoacetate
3HB
Acetone
o 2 Acetyl CoA forms Acetoacetyl CoA
o Moved back to muscles and reverted back to 2 acetyl CoA
o Used in starvation, brain also uses ketone bodies
Carbs and proteins in exess can be converted to fatty acids stored as TAG
Fatty acid synthesis occurs in liver and lactating mammary glands
o In cytosol, whereas beta-oxidation is in mitochondria
o Grows 2 carbons at a time
o ATP and NADPH needed to synthesize fatty acid
o NADPH from pentose phosphate pathway
Metabolic Pathway in Liver:
o Glucose enters liver from GLUT-2
o Glucose becomes G-6-P by glucokinase
o G-6-P goes to PPP or to Pyruvate
o Pyruvate goes to Citric Acid Cycle or Fatty Acid Synthesis
o Inhibition of Isocitrate DH in CAC allows use of Acetyl CoA Carboxylase for fatty
acid synthesis
o High levels of Citrate will allosterically activate fatty acid synthesis
During synthesis:
o Ketone groups reduced to hydroxyl groups by NADPH
o Reduce double bonds to single bonds uses NADPH
o Adds 2 carbons at a time
o NADPH is generated by
PPP
When Malate turns to Pyruvate
Uses of NADPH:
o Reductive synthesis: fatty acids, steroids, sterols
o Cytochrome P450 system
o Detox of reactive oxygen intermediate
Further elongation of fatty acid occurs in smooth ER
o Can add cis double bonds to produce oleic acid (18:1(9))
Fatty acids regulate gene expression by binding to nuclear transcription factors: peroxisome
proliferator-activated receptors (PPARs)