Week 1 Flashcards
What is made from organic material?
Amino acids, nucleic acids, lipids, sugars, phosphate
What does metabolism do?
Breaks down macromolecules to simple, cell usable molecules.
What elements makeup 99% of cell mass?
H (1 bond)
O (2bond)
N (3 bonds)
C (4 bonds)
What are stereoisomers?
- stereospecific
- cis or trans
What is a mirror image stereoisomer?
Enantiomer, has identical chemical characterisitics.
What is not a mirror image stereoisomer?
Diastereomer, different chemical characteristics.
What is an example of a stereoisomer?
Glucose with hexokinase, ligand with hormone, antibody with antigen
When gibbs free eneregy is negative, the reaction proceeds?
Forward
When gibbs free energy is zero, the reaction proceeds?
Equilibrium
When gibbs free energy is postivive, the reaction proceeds in ?
Reverse
What are the 5 reaction types in metabolism?
make/break C-C bond Internal rearrangements free radical reactions group transfers oxidation-reduction reactions
What are the 2 ways to break a covalent bond?
Homolytic(even distribution)
Heterolytic (uneven distribution of e-)
Nucleophiles are rich in ? and donate what?
Electrons
Electrophiles are deficient in? and accept what?
Electrons
What is both an electrophile and a nucleophile?
Carbon
What is the increase in electronegativity gradient?
H
What are more reduced compounds rich in ?
Hydrogen
What are more oxidised compounds rich in ?
Oxygen
What is the most oxidised carbon state?
Carbon dioxide
What is the most reduced carbon dioxide?
CH4
What happens to metabolism energy ?
It is harvested and reutilised.
What type of classification do humans have based on their energy source?
chemoheterotroph
What is strongly favourable?
The complete oxidation of reduced compounds (glucose) is strongly favorable.
What can energy stored in reduced organic compounds do?
It can be used to reduce cofactors such as NAD+ and FAD, which serve as universal electron carriers.
What are the four ways in which electrons are passed from electron donors to electron acceptors?
- directly as electrons
- as hydrogen atoms
- as hydride ions (2 electrons)
- by a combination of organic reductants with O2.
What electrons carrriers are also coenzymes that undergo oxidation/reduction reactions in electron transfer reactions?
NAD, NADP, FAD, FMN
What is catabolism?
Primarily energy-producing
What is anabolism?
Primarily using energy to build complex structures –> anabolism/biosynthesis
What does cellular metabolism provide ?
energy:
- electrons, reducing power: NADPH, NADH, FADH
- chemical energy - ATP
- Inorganic phosphate
- other carriers
What cofactors drive proton motive force and in what process? What do they produce?
NADH, FADH
Process: oxidative phosphorylation
ATP
What can ATP be regenerated from?
Substrate level phosphorylation by kinase enzymes
What are the two bonds in ATP?
Phosphoanhydride bonds
What drives reaction such as muscle contraction?
Hydrolysis of ATP
What does all catabolism and anabolism converge on ?
Acetyl Co A oxidation, pxphos to produce ATP and Co2
What are the smallest components of proteins and what are they linked by ?
Amino acids and peptide bonds
What are the smallest components of nucleic acids and what are they linked by ?
Nucelotides and phosphodiester bonds
What are the smallest components of polysaccharides and what are they linked by?
monosaccharides and glycosidic bonds
What are the two types of enzymes?
proteins and catalytic RNAs
What is an energy-requiring reaction called?
endergonic
What is an energy-releasing reaction called?
exergonic
What is the energy of hydrolysis for each inorganic phosphate?
-7.3kcal/mol
What are metabolic pathways?
They are conserved and are interconnected
What are the catabolic/convergent pathways?
transform fuels into cell energy, glycolysis and TCA cycle
What are the divergent/anabolic pathways?
Fatty acid biosynthesis
What are the waste disposal pathways?
Removal of NH3 during the catabolism of amino acids via the urea cycle
What do metabolic pathways converge on?
Acetyl co A
What effects on the fed/fasted state are on glycolysis?
There is a need to increased the capacity of glycolysis during the action (fed state), there is then a need to reduce the capacity of glycolysis after the action (fasted state). Need to increase the capacity of a different reaction, gluconeogenesis after successful action (when blood glucose is low in fasted state)
Are cells isothermal and if so what does it mean?
They maintain a constant temperature and there is a controlled energy release.
Irreversible reactions are?
Thermodynamically unfavourable
How do cells regulate catabolism and anabolism?
irreversible reactions
unique enzymes
compartmentalization
feedback control
What is allostery?
This is where allosteric enzymes are regulated by molecules called effectors that bind non-covalently at a site other than the substrate binding/active site
What is the rate limiting enzyme for the conversion of threonine to isoleucine?
Isoleucine
What inhibits the commitment step of glycolysis?
ATP
What processes occur in the mitochondria?
TCA cycle
Fatty acid oxidation
Oxidation of pyruvate
What processes occur in the cytosol?
Glycolysis
PP pathway
Fatty acid synthesis
What are the three functions of carbohydrates?
Energy storage, membrane components - signaling and structure, exoskeleton and cellulose
What is a branched polymer of glucose?
Glycogen and cellulose
What is an unbranched polymer of glucose?
Cellulose
What enzyme joins hexoses together to form disaccharides?
glycosyltransferases
What enzymes are involved in the hydrolysis of a glycosidic bond?
glycoside hydrolases
Glycosidases:
alpha amylase - a(1-4)
no enzyme for - B(1-4)
What are the four specific disaccharides involved in the digestion of carbohydrates in food?
isomaltose
maltase
sucrase
trehalose
What are the specific transporters for different sugars?
GLUT - glucose transporter
SGLT - sodium dependent glucose transporter
What does GLUT 2 do?
brings glucose from cells to portal circulation (glucose release to blood)
What does glut 4 do?
transports glucose to the muscles and adipose tissue, increased uptake with insulin
What are the 4 significant fates of glucose?
structure, storage (FED), nucleic acid synthesis, energy and metabolic intermediates (pyruvate to acetyl co A and Glycolysis (FED/FASTED)
Describe aerobic glycolysis?
glycolysis - pyruvate to acetyl Co A to mitochondria to ATP, ETC, OXPHOS
Describe anaerobic glycolysis?
glycolysis - pyruvate - lactate, occurs in cells lacking mitochondria and oxygen such as erythrocytes
What does glycolysis do?
It is where reduced NADH needs to be recycled.
What is the first step of glycolysis?
Phosphorylation of glucose to glucose 6 phosphate, traps glucose in the cytosol.
What is the net yield of glycolysis?
2 pyruvate from one glucose
2 ATP from 2 ADP
2 NADH from 2 NAD
In the prep phase what is the phosphoryl donor?
ATP
In the pay off phase what is the phosphoryl donor?
Inorganic phosphate
Where does the energy payoff come through?
ATP formation
NADP formation
What are some examples of negative feedback on glycolysis?
glucose 6 P
High ATP
Citrate
Glucokinase regulatory protein
Under anaerobic conditions, what is pyruvate reduced to?
Lactate and ethanol
What is lactic acidosis?
- elevated concentrations of lactate in the plasma when there is a collapse in the circulatory system - lack of oxygen supply to the tissues and cells - myocardial infarction, pulmonary embolism, uncontrolled hemorrhage
Can lactate be used to synthesise glucose?
Yes
What is the Warburg Effect?
Cancer cells and tissues have a very active anaerobic glucose catbolism even in the presence of oxygen.
What glycolytic enzyme was at an increased level in cancer tissues?
Hexokinase and glucose transporters
What is the role of HIFa in the Warburg Effect?
Hypoxia Inducing Factor - transcription factor strong role in the upregulation of HK and GLuT in tumours
What are the 3 therapies which exploit glycolysis?
2 deoxyglucose
Ionidamine
3-bromopyruvate
What are the three regulatory enzymes in glycolysis?
Hexokinase
phosphofructokinase
pyruvate kinase
What is an acetyl group?
COCH3
What do you see in the fed state?
Insulin ATP levels NADH and NADPH levels Citrate Oxaloacetate
What do you see in the fasted state?
Glucagon
ADP levels and Pi
NAD and NADP levels Ca2+
Which GLUT transporter is seen with increased uptake of insulin?
Glut 4 –> Muscles and adipose tissue
Where does glycolysis occur?
In the cytoplasm
The addition of what to glucose by the enzyme traps glucose inside the cell for glycolysis?
Charged Phosphate Group
What are the three possible fates of pyruvate?
- 2 acetyl CoA
- 2 Lactate
- 2 ethanol and 2 CO2
Which glucose transporter is not released into the plasma membrane in type 1 diabetes?
GLUT 4
What happens if too much insulin is released?
Hyperinsulinemia… irreversible brain damage.
