Bayo-came-stray Flashcards
accelerate chemical reactions by decreasing the energy of activation of the reaction.
Enzymes
is the amount of energy required to produce a transition state and bring about a reaction
Energy of activation (Ea)
Classes of Enzymes
Oxidoreductases
Transferases
Transferases
Hydrolases
Lyases
Isomerases
Enzymes that catalyze OXIDATIONS and REDUCTIONS
Oxidoreductases
Enzymes that catalyze TRANSFER of moieties such as glycosyl, methyl, or phosphoryl groups
Transferases
Hydrolases
Hydrolases Enzymes that catalyze HYDROLYTIC CLEAVAGE of C-C, C-O, C-N and other covalent bonds
Enzymes that catalyze CLEAVAGE of C-C, C-O, C-N and other covalent bonds by atom elimination, generating double bonds
Lyases
Enzymes that catalyze GEOMETRIC or STRUCTURAL CHANGES within a molecule
Isomerases
Enzymes that catalyze joining together (Ligation) of 2 molecules in reactions coupled to the hydrolysis of ATP
Ligases
As substrate binds, enzyme undergoes a conformational change that repositions amino acids in the active site and increases interactions with the substrate – Active site assumes shapes that are complementary to that of the substrate only after the substrate is bound
Flexible Model
the velocity approached at a saturating concentration of the substrate
Vmax
is the concentration of the substrate required to produce 1/2 Vmax
Km
Relates initial velocity to substrate concentration [S] and maximum velocity
Michaelis Menten Equation
vi = Vmax [ S]
Km + [S]
Derived from the reciprocal of the Michaelis Menten equation
Lineweaver Burk Equation
Effects of Inhibitors on Km and Vmax
Km increases and Vmax constant
Competitive Inhibition
To overcome: increase concentration of substrate
Effects of Inhibitors on Km and Vmax
Km constant and Vmax decreases
To overcome: reversible or irreversible depending on whether the inhibitor binds temporarily or indefinitely.
interferes with the active site of an enzyme so substrate cannot bind
Competitive inhibitor
- changes shape of the enzyme so it cannot bind to substrate
Non-Competitive inhibitor
Contain “active sites”
May act as the second substrate
Recover original state at the end of the reaction •
Mostly derived from vitamins (deficiencies may result to impaired metabolism)
COENZYMES
Non protein organic portion of enzyme
Heat stable, low MW
Help enzymes accelerate reactions • Accept and transfer functional group
Coenzymes that participate in transfer of H+ and electrons
- NAD/NADP 2. FAD/FMN 3. Ubiquinone or Coenzyme Q 4. Tetrahydrobiopterin
Coenzymes that participate in transfer of groups other than H+ and electrons
- Transfer of acyl groups and active aldehydes, TPP, Lipoic acid, Coenzyme A
- Amino group transfer Pyridoxal Phosphate
- Activation and transfer of CO2- Biocytin
- Transfer of one carbon compounds- Tetrahydrofolate
- Transfer of Alkyl groups – Cobamide (B12) coenzyme
Composed of a nucleotide (AMP) and a pseudonucleotide, nicotinamide
• Derived from Nicotinic Acid or Niacin
• Active site is found at C4 of the pyridine ring
• NAD is utilized by specific enzymes • Lactate dehydrogenase • Malate dehydrogenase
• NADP is involved in: Lipid and nucleic acid synthesis
• Reductive biosynthesis
• Glucose-6-PO4 dehydrogenase
Nicotinamide Adenine Dinucleotide
Composed of an isoalloxazine ring
• Contains ribitol, instead of ribose
• Derived from Vitamin B2 or Riboflavin
Flavin Mononucleotide Flavin Adenine Dinucleotide FAD/FMN
Ubiquinone (Coenzyme Q)
• Ubiquitous, lipid soluble coenzyme Of the electron transport chain
• Benzoquinone with side chains of Repeating isoprenoid units
• Involved in the reaction catalyzed by (Complex I) of the ETC
Ubiquinone (Coenzyme Q)
• Synthesized from Biopterin.
Involved in hydroxylation reactions catalyzed by:
1-Phenylalanine Hydroxylase
2- Tryptophan Hydroxylase
Tetrahydrobiopterin
Derived from vitamin B1 (thiamine)
• Consists of a substituted pyridine linked to thiazole ring with a terminal phosphate
• Requires Mg ++ for activity
• Inactivated by thiaminase found in raw fish
THIAMINE PYROPHOSPHATE
3 Enzyme catalyzed reactions that require TPP
- Non-oxidative Decarboxylation of Pyruvic Acid – Pyruvic acid decarboxylase
- Transketolation – transketolase
- Oxidative Decarboxylation of Pyruvic Acid- dehydrogenase
> Derived from Pantothenic acid
>Participates in acyl group transfer
Coenzyme
Composed of:
§ AMP linked to a pyrophosphate
§ Pantoic Acid + b-Alanine
§ Thioethanolamine
Involved in reactions catalyzed by:
§ Fatty Acyl CoASH synthase
§ Pyruvate dehydrogenase Complex
Derived from Biotin • Consists of:
– Imidazole ring fused with tetrahydrothiophene – Valeric Acid
• Synthesis is inhibited by Avidin, a protein in raw egg white Pyruvate
• Associated with Carboxylation reactions or transfer of Carboxyl groups
1. Acetyl CoA Carboxylase
2.Pyruvate Carboxylase
Biocytin
Involved in Amino Acid Reactions:
ü Transamination-
ü Decarboxylation-
ü Racemization-
Transamination- Alanine transaminase
Decarboxylation- Amino Acid decarboxylase
Racemization- Amino Acid racemase
Involved in one-Carbon group transfer except CO2
Synthesis is inhibited by folate antagonists e.g. methotrexate, sulfonamides
Tetrahydrofolic acid
Derived from Folic Acid • Consists of:
– Substituted Pteridine – P-Amino benzoic Acid (PABA)
– Glutamic Acid
Tetrahydrofolic acid
1.Derived from Vitamin B12 or Cyanocobalamin 2.Consists of a tetrapyrrole ring with a central Cobalt atom
Cobamide Coenzyme
Two coenzyme forms:
- Deoxyadenosylcobalamin (Isomerization)
* Methylcobalamin (Methyl Transferase Reaction)
PEROXISOMES / PIPECOLATE OXIDASE
ZELLWEGER DISEASE
GLUCOSE-6-PHOSPHATASE
VON GIERKE’S - GSD TYPE I
LYSOSOMAL ACID MALTASE
POMPE’S - GSD TYPE II
α-1,6-GLUCOSIDASE
CORI’S - GSD TYPE III
CANAVAN DISEASE
ASPARTOACYLASE
MUSCLE PHOSPHORYLASE
McArdle’s - GSD TYPE V
TARUI’S DISEASE
PHOSPHOFRUCTOKINASE
> At physiological pH (~7), >Doubly-charged species –
zwitterion
At physiological pH (~7),
Can act either as acid or base –
AMPHOTERIC
Major Pathway for Glucose Metabolism
Glycolysis
Embden Meyerhoff Parnas Pathway)
Occurs in cells with mitochondria
With adequate supply of oxygen
2 molecules of NADH are formed when pyruvate is produced
AEROBIC GLYCOLYSIS
Tissues without mitochondri With adequate supply of oxygen mitochondria
Without oxygen
NADH is reconverted to NAD + when lactate is the end product
ANAEROBIC GLYCOLYS
Functions of Glycolysis
Tissues that depend on glycolysis as their major mechanism for ATP production:
– RBC, cornea, lens, regions of the retina= they lack mitochondria
– Kidney medulla, testis, leukocytes and white muscle fibers= few mitochondria
- almost totally dependent on glycolysis
WHICH OF THE FOLLOWING REACTIONS IS INHIBITED BY ITS PRODUCT? WHAT IS THE ENZYME?
A. GLUCOSE 6-PHOSPHATE → FRUCTOSE 6-PHOSPHATE
B. GLUCOSE → GLUCOSE 6-PHOSPHATE
C. FRUCTOSE 6-PHOSPHATE → FRUCTOSE 1,6-BISPHOSPHATE
• ↓glucagon, ↑ insulin = ↑ fructose 2,6 bisphosphate = ↑ glycolysis
Well fed state
↑ glucagon, ↓ insulin = ↓ fructose 2,6 bisphosphate = ↓ glycolysis
Starvation
MOA: competing with inorganic phosphate as substrate for G3P dehydrogenase → complex that spontaneously hydrolyzes to form 3-phosphoglycerate
• Bypassing of the synthesis and dephosphorylation of 1,3 BPG: cell deprived of energy
ARSENIC POISONING
dependent on the presence if Mg or Mn)
• Redistributes the energy within the 2-phosphoglycerate molecule
• Phosphoenolpyruvate (PEP): contains high energy enol phosphate
• Reversible
• Inhibited by Fluoride
Enzyme: Enolase
Potent inhibitor of ENOLASE
FLUORIDE
Inhibits those enzymes which require LIPOIC ACID as coenzyme like pyruvate dehydrogenase, alpha ketoglutarate dehydrogenase
ARSENIC POISONING
• 2nd most common cause of enzymatic related hemoyltic anemia • Restricted to erythrocytes, producing mild to severe hemolytic anemia
Severity : depends on the degree of enzyme deficiency and on the extent to which individual’s compensate by synthesizing 2, 3 BPG
• Mutant enzyme with abnormal properties
PYRUVATE KINASE DEFICIENCY
