如果这种基因突变恰好发生在生殖细胞或受精卵中,就有可能传递给 后代,从而使后代产生相应的先天性代谢缺陷( inborn errors of metabolism)或遗传性酶病( hereditary enzy mopathy)。 Enzyme Deficiencies and Disease: General Descriptions 1. Enzy mopathies are almost always recessive Most enzymes are produced in quantities significantly in excess of minimal biochemical requirements, so that heterozy gotes with about 50%0 of residual activ ity are clinically normal. In fact, many enzymes may maintain normal substrate and product level with activ ities of less than 10%. The enzymes of porphyrin synthesis are exceptions, an observation which is understandable when it is recognized that they can each limit the rate of porphyrin synthesis 2. Substrate accumulation or product deficiency Because the function of an enzyme is to convert a substrate to a product, all of the pathophysiological consequences of enzymopathies can be attributed either to the accumulation of the substrate. to the deficiency of the product, or to some combination ofthe two 3. Diffusible versus macromolecular substrate An important distinction can be made between enzyme defects in which the substrate is asmall molecule, such as pheny lalanine that can be readily distributed throughout body fluids by diffusion or transport, and defects in which the substrate is a macromolecule. such as a mucopolysaccharide, that remains trapped within its organelle or cell. The anthology of the macromolecular diseases is confined to the tissues which the substrate accumulates. whereas the site of the disease in the small molecule disorders is often unpredictable because the unmetabolized substrate, or its derivatives, can move freely throughout the body damaging cells that may normally have no relationship to the affected enzyme 4. Loss of multiple enzy me activities A single patient may have defects in more than one enzyme. There are several possible mechanisms: (1 several enzymes may utilize the same cofactor(e.g, BH4 deficiency ):@2 two or more enzymes may share a common subunit or activating, processing, or stabilizing protein(e.g, the GM2 gangliosidoses ) multiple enzymes may be processed by a common modify ing enzyme, and in its absence they may not become active, or their uptake into an organelle may be impaired (e.g, I-cell disease);and(4 a group of enzymes may be absent or ineffective if the10 如果这种基因突变恰好发生在生殖细胞或受精卵中，就有可能传递给 后代，从而使后代产生相应的先天性代谢缺陷（inborn errors of metabolism）或遗传性酶病（hereditary enzymopathy）。 Enzyme Deficiencies and Disease: General Descriptions 1.Enzymopathies are almost always recessive. Most enzymes are produced in quantities significantly in excess of minimal biochemical requirements, so that heterozygotes with about 50% of residual activity are clinically normal. In fact, many enzymes may maintain normal substrate and product level with activities of less than 10%. The enzymes of porphyrin synthesis are exceptions, an observation which is understandable when it is recognized that they can each limit the rate of porphyrin synthesis. 2.Substrate accumulation or product deficiency. Because the function of an enzyme is to convert a substrate to a product, all of the pathophysiological consequences of enzymopathies can be attributed either to the accumulation of the substrate, to the deficiency of the product, or to some combination of the two. 3.Diffusible versus macromolecular substrate. An important distinction can be made between enzyme defects in which the substrate is a “small” molecule, such as phenylalanine, that can be readily distributed throughout body fluids by diffusion or transport, and defects in which the substrate is a macromolecule, such as a mucopolysaccharide, that remains trapped within its organelle or cell. The pathology of the macromolecular diseases is confined to the tissues in which the substrate accumulates, whereas the site of the disease in the small molecule disorders is often unpredictable because the unmetabolized substrate, or its derivatives, can move freely throughout the body, damaging cells that may normally have no relationship to the affected enzyme. 4.Loss of multiple enzyme activities. A single patient may have defects in more than one enzyme. There are several possible mechanisms:① several enzymes may utilize the same cofactor (e.g., BH4 deficiency); ② two or more enzymes may share a common subunit or activating, processing, or stabilizing protein (e.g., the GM2 gangliosidoses); ③ multiple enzymes may be processed by a common modifying enzyme, and in its absence they may not become active, or their uptake into an organelle may be impaired (e.g., I-cell disease); and ④ a group of enzymes may be absent or ineffective if the