1. Organic chemistry of metabolic pathways

2. Book: Bruice
Chapter: 20

3. 2 types: catabolism and anabolism
Metabolism - reactions that living organisms carry out to obtain the energy they need and to synthesize the compounds they require
2 types: catabolism and anabolism
Catabolism: complex molecules -> simple molecules +energy
Anabolism: simple molecules+energy -> complex molecules

4. every reaction that occurs in a living system is catalyzed by an enzyme
holds the reactants and any necessary coenzymes in place
orienting the reacting functional groups
Catalyzing amino acid side chains in such a way that the enzyme-catalyzed reaction can take place

5. Digestion
reactants required for all life processes ultimately come from our diet
Catabolism – 4 stages
1. digestion – hydrolysis (mouth, stomach, small interstine)

6. 2. conversion of products from the first stage
Converted compunds enter the citric acid cycle
compound must be either one of the compounds in the cycle itself - acetyl-CoA or pyruvate

7. 3. citric acid cycle
acetyl group of each molecule of acetyl-CoA is converted to two molecules of CO2
Metabolic energy is measured in terms of ATP
Small amount formed in first 3 stages

8. 4. every molecule of NADH formed in one of the earlier stages of catabolism is converted into three molecules of ATP in a process called oxidative phosphorylation
most of the energy (ATP) provided by fats, carbohydrates, and proteins is obtained in the fourth stage of catabolism

9. ATP - PHOSPHORYL TRANSFER REACTIONS
Without ATP, many important biological reactions could not occur
Example: reaction of glucose with hydrogen phosphate to form glucose-6-phosphate
does not occur because the 6-OH group of glucose would have to displace a very basic OH-group from hydrogen phosphate

10. ATP present - 6-OH group of glucose attacks the terminal phosphate of ATP, breaking a phosphoanhydride bond
weaker bond than the pi-bond
SN2 reaction
ADP is a very good leaving group
transfer of a phosphoryl group from ATP to glucose is an example of a phosphoryl transfer reaction

11. Conclusion: importance of ATP
provides a reaction pathway involving a good leaving group for a reaction that cannot occur (or would occur very slowly) because of a poor leaving group.

12. The catabolism of fats Fats – 3 ester groups
1. step – hydrolyzed by enzymes to glycerol and three fatty acid molecules

13. Glycerol reacts with ATP to form glycerol-3-phosphate
Enzyme for catalysis – kinase
puts a phosphoryl group on its substrate

14. Secondary alcohol group - oxidized to a ketone
NAD+ oxidizing agent
Enzyme for catalysis – dehydrogenase
Oxidizes its substrate
Product: one of the compounds in the glycolytic pathway

15. Activation of fatty acids
In order to be metabolized
activated by being converted into a thioester

16. The fatty acid reacts with ATP, in a phosphoryl transfer reaction - the product is an acyl phosphate
The acyl phosphate reacts with CoASH in a nucleophilic acyl substitution reaction

17. acyl-CoA is converted to acetyl-CoA
In repeating process – β-oxidation
Series of 4 reactions
Each removes two carbons from the fatty acyl-CoA by converting them into acetyl-CoA
Different enzymes

18. The catabolism of carbohydrates
In the first stage of catabolism - acetal groups that hold glucose subunits together are hydrolyzed
Formation of individual glucose molecules

19. Glucose is further on converted to pyruvate
Glycolysis or glycolytic pathway (biochemistry)

20. The fates of pyruvate NAD+ used as oxidizing agent in glycolysis
NADH produced – needs to be oxidized back to NAD+
If oxygen is present it serves as oxidizing agent
If it is not present (in muscle cells when intense muscle activity causes all the oxygen to be depleted) – pyruvate serves as oxidizing agent
Reduced to lactic acid

21. In aerobic conditions when oxygen is used - pyruvate is converted to acetyl-CoA
Enters the citric acid cycle
catalyzed by the pyruvate dehydrogenase system
requires three enzymes and five coenzymes

22. In anaerobic conditions pyruvate is reduced to lactate
In yeast - decarboxylated to acetaldehyde by pyruvate decarboxylase
acetaldehyde is the compound that oxidizes NADH back to NAD+
Reduced to ethanol – for the production of alcohol beverages

23. Solve the problems

24. The catabolism of proteins
First stage – proteins hydrolyzed to amino acids
Second stage - amino acids are converted to acetyl-CoA or pyruvate or citric acid cycle intermediates
Products of second stage - enter the citric acid cycle
Further metabolized

25. Example: catabolism of Phenylalanine
Phe – one of essential amino acids
Must be included in our diet
phenylalanine hydroxylase converts phenylalanine into tyrosine
Tyrosin involved in other metabolic pathways

26. Chemistry link: phenylketonuria
Babies born without phenylalanine hydroxylase
Genetic disorder – phenylketonuria
level of phenylalanine builds up - transaminated to phenylpyruvate (found in urine)
In USA - tested for high serum phenylalanine levels immediately after birth
High levels present - diet low in phenylalanine and high in tyrosine
phenylalanine level is kept under careful control for the first 5 to 10 years of life, the child will experience no adverse effects

27. If the diet is not controlled - the baby will be severely mentally retarded by the time he or she is a few months old
Untreated children - cannot synthesize melanin
Half of untreated children - dead by age 20

28. Chemistry link: Alcaptnouria
Genetic disease
results from a deficiency of an enzyme in the pathway for phenylalanine degradation
Caused by lack of homogentisate dioxygenase
only ill effect – black urine
Homogentisate they excrete immediately oxidizes in the air – forming a black compound

29. Anabolism Reverse of catabolism
acetyl-CoA, pyruvate, and citric acid cycle intermediates are the starting materials
For the synthesis of: fatty acids, monosaccharides, and amino acids
compounds are then used to form fats, carbohydrates, and proteins

30. Problems
Indicate whether an anabolic pathway or a catabolic pathway does the following:
a. produces energy in the form of ATP
b. involves primarily oxidation reactions

31. Summary Metabolism Anabolism Catabolism Catabolism of fats
Catabolism of proteins
Catabolism of carbohydrates

32. Structure of atom
Chemical bonds
PSE
Isotopes
Electronic configuration
Formal charge
Electronegativity
Bond polarity
Sigma bond
Pi bond
MO theory
Bonding/antibonding orbitals
Hybridization and molecular shapes
Conjugated Pi-bonds
Aromaticity
Non covalent interactions
Dipole moments
Boiling point and branching
Solubility
Acids and bases
pH and pKa
Resonance contributor
Resonance hybrid
Predicting stability
Delocalized electrons/energy
UV/Vis
Conjugated Pi-bonds and λmax
Chirality
Stereoisomers
Asymmetric C atom
Assigning priorities
R or S isomer?
SN1 and SN2 mechanisms
Application in enzyme catalysis
IR spectroscopy
Parts of IR spectrum (alcohols, amines, fingerprint region etc.)
Mass spectrometry
Parts of MS spectrum (base peak etc.)
Coupling GC/MS
Structure of amino acids
Zwitterion
Isoelectric point
Synthesis of amino acids
Determination of amino acids
Solution phase peptide synthesis
Solid phase peptide synthesis
Levels of protein structure
Anabolism and catabolism
Catabolism of fats, proteins and carbs
Fates of pyruvate
Stages of digestion
Enzymes
Coenzymes
Vitamins
Water and fat soluble vitamins
Importance and deficiency of vitamins