456 Chapter 15 Enzyme Regulationpro

456 Chapter 15 Enzyme Regulation
properties of the various LDH isozymes differ in terms of their relative affinities
for the various substrates and their sensitivity to inhibition by product. Different
tissues express different isozyme forms, as appropriate to their particular meta-
bolic needs. By regulating the relative amounts of A and B subunits they synthe-
size, the cells of various tissues control which isozymic forms are likely to assemble
and thus which kinetic parameters prevail.
15.2 What Are the General Features
of Allosteric Regulation?
Allosteric regulation acts to modulate enzymes situated at key steps in metabolic
pathways. Consider as an illustration the following pathway, where A is the precur-
sor for formation of an end product, F, in a sequence of five enzyme-catalyzed
reactions:
enz 1 enz 2 enz 3 enz 4 enz 5
A ⎯⎯→ B ⎯⎯→ C ⎯⎯→ D ⎯⎯→ E ⎯⎯→ F
In this scheme, F symbolizes an essential metabolite, such as an amino acid or a nu-
cleotide. In such systems, F, the essential end product, inhibits enzyme 1, the first step
in the pathway. Therefore, when sufficient F is synthesized, it blocks further synthe-
sis of itself. This phenomenon is called feedback inhibition or feedback regulation.
Regulatory Enzymes Have Certain Exceptional Properties
Enzymes such as enzyme 1, which are subject to feedback regulation, represent a
distinct class of enzymes, the regulatory enzymes. As a class, these enzymes have cer-
tain exceptional properties:
1. Their kinetics do not obey the Michaelis–Menten equation. Their v versus [S] plots
yield sigmoid- or S-shaped curves rather than rectangular hyperbolas (Figure
15.6). Such curves suggest a second-order (or higher) relationship between v and
[S]; that is, v is proportional to [S]n, where n 1. A qualitative description of the
mechanism responsible for the S-shaped curves is that binding of one S to a pro-
tein molecule makes it easier for additional substrate molecules to bind to the
same protein molecule. In the jargon of allostery, substrate binding is cooperative.
2. Inhibition of a regulatory enzyme by a feedback inhibitor does not conform to
any normal inhibition pattern, and the feedback inhibitor F bears little structural
similarity to A, the substrate for the regulatory enzyme. F apparently acts at
(a) The five isomers of lactate dehydrogenase
A4
A3B
A2B2
AB3
B4
(b) A4 A3B A2B2 AB3 B4
Liver
Muscle
White cells
Brain
Red cells
Kidney
Heart
ACTIVE FIGURE 15.5 The isozymes of
lactate dehydrogenase (LDH). Active muscle tissue
becomes anaerobic and produces pyruvate from glucose
via glycolysis (see Chapter 18). It needs LDH to regenerate
NAD from NADH so that glycolysis can continue.The
lactate produced is released into the blood.The muscle
LDH isozyme (A4) works best in the NAD-regenerating
direction. Heart tissue is aerobic and uses lactate as a fuel,
converting it to pyruvate via LDH and using the pyruvate
to fuel the citric acid cycle to obtain energy.The heart
LDH isozyme (B4) is inhibited by excess pyruvate so that
the fuel won’t be wasted. Test yourself on the con-
cepts in this figure at www.cengage.com/login.
v
[S]
Hyperbolic
Sigmoid
V max
FIGURE 15.6 Sigmoid v versus [S] plot. The dotted line
represents the hyperbolic plot characteristic of normal
Michaelis–Menten-type enzyme kinetics.

Kết quả (Việt) 1:

456 chương 15 Enzyme quy địnhthuộc tính của LDH isozymes khác nhau khác nhau trong điều kiện của duyên tương đốicho chất nền khác nhau và họ nhạy cảm với sự ức chế của sản phẩm. Khác nhauMô nhận các hình thức khác nhau isozyme, như là thích hợp để meta cụ thể của họ-nhu cầu bolic. Bởi quy định một lượng tương đối của A và B subunits họ synthe -Kích thước, các tế bào của các điều khiển mô hình thức isozymic mà có khả năng lắp rápvà vì thế những tham số động ưu tiên áp dụng.15.2 tính năng nói chung là gì Allosteric quy định?Allosteric quy định hành vi để điều chỉnh enzyme nằm ở bước quan trọng trong trao đổi chấtcon đường. Xem xét như là một minh hoạ con đường sau, nơi A là precur -Sor cho hình thành của một sản phẩm cuối cùng, F, theo một thứ tự của 5 enzyme xúc tác phản ứng:Enz 1 enz 2 enz 3 enz 4 enz 5A ⎯⎯→ B ⎯⎯→ C ⎯⎯→ D ⎯⎯→ E ⎯⎯→ FTrong chương trình này, F tượng trưng cho một chất chuyển hóa cần thiết, chẳng hạn như một acid amin hay một nu-cleotide. Trong hệ thống như vậy, F, sản phẩm cuối cùng cần thiết, ức chế enzym 1, bước đầu tiêntrong con đường. Vì vậy, khi đủ F được tổng hợp, nó chặn tiếp tục synthe-sis của chính nó. Hiện tượng này được gọi là phản hồi ức chế hay quy định thông tin phản hồi.Quy định enzym có một số đặc tính đặc biệtEnzym như enzyme 1, mà có thể để quy định thông tin phản hồi, đại diện cho mộtkhác biệt lớp của các enzym, các enzym quy định. Như là một lớp học, các enzym có cer-tain exceptional properties:1. Their kinetics do not obey the Michaelis–Menten equation. Their v versus [S] plotsyield sigmoid- or S-shaped curves rather than rectangular hyperbolas (Figure15.6). Such curves suggest a second-order (or higher) relationship between v and[S]; that is, v is proportional to [S]n, where n 1. A qualitative description of themechanism responsible for the S-shaped curves is that binding of one S to a pro-tein molecule makes it easier for additional substrate molecules to bind to thesame protein molecule. In the jargon of allostery, substrate binding is cooperative.2. Inhibition of a regulatory enzyme by a feedback inhibitor does not conform toany normal inhibition pattern, and the feedback inhibitor F bears little structuralsimilarity to A, the substrate for the regulatory enzyme. F apparently acts at (a) The five isomers of lactate dehydrogenaseA4A3BA2B2AB3B4(b) A4 A3B A2B2 AB3 B4LiverMuscleWhite cellsBrainRed cellsKidneyHeartACTIVE FIGURE 15.5 The isozymes oflactate dehydrogenase (LDH). Active muscle tissuebecomes anaerobic and produces pyruvate from glucosevia glycolysis (see Chapter 18). It needs LDH to regenerateNAD from NADH so that glycolysis can continue.Thelactate produced is released into the blood.The muscleLDH isozyme (A4) works best in the NAD-regeneratingdirection. Heart tissue is aerobic and uses lactate as a fuel,converting it to pyruvate via LDH and using the pyruvateto fuel the citric acid cycle to obtain energy.The heartLDH isozyme (B4) is inhibited by excess pyruvate so thatthe fuel won’t be wasted. Test yourself on the con-cepts in this figure at www.cengage.com/login.v[S]HyperbolicSigmoidV maxFIGURE 15.6 Sigmoid v versus [S] plot. The dotted linerepresents the hyperbolic plot characteristic of normalMichaelis–Menten-type enzyme kinetics.