Enzimas

Fernando L. Palhano
Fernando Palhano – palhano@bioqmed.ufrj.br
Sala E42, Fone: 3938 6761
Data Tópico
28 de Outubro Estrutura de proteínas
03 de Novembro Estrutura de proteínas
04 de Novembro Estrutura de proteínas
16 de Novembro Estrutura de proteínas
17 de Novembro Estrutura de proteínas
18 de Novembro Prova (1/2) 9:00 - 12:00 hs
23 de Novembro Enzimas
24 de Novembro Enzimas
25 de Novembro Enzimas
30 de Novembro Equilibrio ácido base

01 de Dezembro Prova (1/2) 9:00 - 12:00 hs

Chave fechadura vs induced fit
A 35-year-old man is brought to the emergency department by his wife aTer ingesUng
automobile anUfreeze in an aVempt at self-harm. On presentaUon, the paUent is
somnolent. He is afebrile and has a blood pressure of 126/72 mm Hg, a pulse rate of
102 beats per minute, and a respiratory rate of 24 breaths per minute. Pulse oximetry
shows a hemoglobin saturaUon of 97% while the paUent is breathing ambient air. His
physical examinaUon is normal except for tachypnea. His serum electrolyte profile
and creaUnine level are normal except for a serum carbon dioxide level of 17 mmol per
liter. Arterial blood gas measurement reveals a pH of 7.30. Urinalysis shows microscopic
hematuria and needle-shaped crystals typical of calcium oxalate. A medical toxicologist
recommends treatment with fomepizole.
Subsequently, the paUent’s serum ethylene glycol concentraUon is determined
to be 580 mg per deciliter (93.4 mmol per liter).

•  The normal respiratory rate rate is 12-20

breaths per minute
•  ref CO2 =22-29 mmol/L
Fomepizole is a
compeUUve inhibitor of
the enzyme alcohol
dehydrogenase, found in
the liver.
 aldehydes are
highly reacKve compounds,
which can form adducts with
proteins, DNA, and lipids,
affecKng the funcKon of these
biomolecules and leading to
cell toxicity
 Aldehyde dehydrogenase (ALDH) 2

•  Aldehyde dehydrogenase (ALDH) 2 is a mitochondrial enzyme that catalyzes the

oxidaUon of acetaldehyde, an intermediate of ethanol metabolism.

•  The Glu504Lys (E504K) single nucleoUde polymorphism (SNP) of ALDH2 gene, which
occurs with an incidence of 35–57% in different East Asian subpopulaUons, causes defect
in the enzyme acUvity of ALDH2, leading to alteraUons in acetaldehyde metabolism and
markedly reduced alcohol tolerance.

Glutamic acid = E
Lysine = K
 Wt E504K

E K

E4 E3K E2K2 EK3 K4

 AKvidade AKvidade
esperada (%) real (%)
Wt 100 100
(E4)
E3K1 75 50

E2K2 50 25

E1K3 25 0

E504K 0 0
(K4)

Isoelectric focusing of human

homotetrameric and heterotetrameric
aldehyde dehydrogenases
Alosteria
M = muscle
B = brain
Lactato desidrogenase
Lactate dehydrogenases. In eukaryote cells, lactate dehydrogenases (LDHs) are tetrameric
enzymes catalyzing the reversible reducUon of pyruvate into lactate. The LDH-B gene is
consUtuUvely transcribed and encodes subunit LDH-H, whereas transcripUon of the LDH-A
gene, which is inducible by hypoxia due to the presence of a consensus HIF-1-binding moUf
(hypoxia-responsive element, HRE), encodes the LDH-M subunit. Arrangement of the subunits
to forms acUve tetramers may lead to the formaUon of five disUnct enzymes, LDH1 to LDH5.
Compared to LDH-H, LDH-M has a higher Km and a higher Vmax for pyruvate reducUon.
Consequently, LDH5/LDH-4M preferenUally catalyzes the reducUon of pyruvate into lactate,
LDH1/LDH-4H preferenUally catalyzes the oxidaUon of lactate into pyruvate, and LDH2, LDH3,
and LDH4 have intermediate enzymaUc acUviUes.
+ Before MI ATer MI

-
The heart uses primarily faVy acids (60% to 80%), lactate, and glucose (20% to 40%) as its
energy sources. Ninety-eight percent of cardiac ATP is generated by oxidaUve means; 2% is
derived from glycolysis. The lactate used by the heart is taken up by a monocarboxylate
transporter in the cell membrane that is also used for the transport of ketone bodies.