Enzyme Structure and Function
Enzyme Structure
Enzymes are primarily made up of hydrogen, nitrogen, carbon, oxygen, sulfur, and phosphorus
all hydrated forms are gaseous (H
2
, NH
3
, CH
4
, H
2
S) except water (H
2
O, due to hydrogen bonding)
Oxidation Spectrum of Carbon
(from least oxidized to most oxidized - less oxidized form produces more energy when oxidized):
CH
4
(methane) – fatty acids, hydrophobic
CH
3
OH (methanol) – sugars
CH
2
O (formaldehyde) – amino acids
HCO
2
H (formic acid)
CO
2
(carbon dioxide)
Hydrophilic vs. hydrophobic
– determined by hydrogen bonding and size (larger is less hydrophilic)
Bonds
(1) ether
– alcohol + alcohol
(2) ester
– acid + alcohol – e.g. acetyl CoA or peptide bond
sulfur ester (Acetyl CoA) is high energy and unstable; nitrogen (peptide) and oxygen are low energy and stable
(3) anhydride
– acid + acid – e.g. phosphodiester bond – high energy
Amino Acids
– very stable due to resonance (double bond can be O=C-N or O
-
-C=N
+
)
have an amino (-NH
3
+
) and an acid (-COO
-
) end – at neutral pH, both are charged –
zwitterion
pK
a
is the pH at which 50% of the acid is ionized
affected by amino acid side groups
some common pK
a
’s:
ionized at physiological pH:
-COOH
(pK
a
= 4)
ionizable at physiologial pH:
histidine ring
(pK
a
= 6),
-SH
(pK
a
= 8)
unionized at phys. pH:
tyrosine (phenyl-OH)
(pK
a
= 10),
-NH
3
(pK
a
= 11),
lysine side chain
(pK
a
= 13)
metabolism of amino acids – lose amino, become lipid or carbohydrate
glycine, alanine
(2-3 carbons)
Þ
pyruvate (CH
3
-CO-CO-OH)
aspartic acid, asparagine
(4 carbons)
Þ
oxaloacetate (HOOC-CO-CH
2
-COOH)
glutamic acid, glutamine
(5 carbons)
Þ
a
-ketoglutarate (HOOC-CO-CH
2
-CH
2
-COOH)
serine,
threonine,
and
tyrosine
are targets of phosphorylation
valine, leucine,
and
isoleucine
are branched chain (isoleucine branches earlier)
phenylalanine
and
tyrosine
contain a phenyl group
cysteine
and
methionine
contain sulfur
glutamine
and
asparagine
do not ionize – have resonance structure (O=C-N or O
-
-C=N
+
)
proline
– secondary amine – disrupts sheets and helices
Enzyme Function
– entirely dependent upon linear sequence of amino acids
Enzymes speed up reactions, often by bringing reactants close together (making it an intramolecular reaction)
ribonuclease
– reaction takes 4 hours at pH 13 to occur spontaneously; enzyme takes minutes at neutral pH
two histidines in close proximity carry out hydrolysis reaction
serine proteases hydrolyze peptide bonds:
trypsin
– C side of basic amino acids – active site has acid
chymotrypsin
– C side of hydrophilic amino acids – active site has hydrophilic phenyl rings
Often, the optimal pH for an enzyme will be different from the pH at its physiological site of action
e.g., trypsin prefers pH = 7.5, but intestinal pH is much higher