Jedziniak J A, Chylack L T, Cheng H M, Gillis M K, Kalustian A A, Tung W H
Invest Ophthalmol Vis Sci. 1981 Mar;20(3):314-26.
The sorbitol pathway in human lenses is evaluated on the enzymic level. Adult lenses, normal and nondiabetic as well as diabetic cataracts, are found to contain limited levels of aldose reductase (AR) and high levels of polyol dehydrogenase (PD) relative to the animal lens. AR is confined primarily to the lens epithelium and is two to three times higher in juvenile lenses than in the adult lens. The level of AR in the epithelium of juvenile lenses is sufficient to cause significant osmotic stress. The Km of glucose of AR is roughly 200 mM, whereas the Km for NADPH is 0.06 mM. NADP inhibits human lens AR noncompetitively and has a Ki equivalent to the Km for NADPH. PD occurs in both the lens epithelium and cortex, remains persistently high with age, and decreases with increased cortical involvement. The Km of sorbitol for PD is 1.4 mM and for NAD is 0.06 mM. NADH (Ki 0.002 mM) competitively inhibits PD in the forward direction. PD purified 100-fold from diabetic and nondiabetic cataracts and normal lenses exhibit similar kinetic constants. PD has an extremely high Vmax in the fructose-to-sorbitol direction. The Km of fructose is 40 mM and for NADH is 0.02 mM. At high enough concentration, alrestatin also inhibits PD. The added activities of AR and PD in producing sorbitol and fructose in combination with decreased hexokinase with age may account for diabetic cataract formation in human lenses exposed to a high glucose stress. Nucleotide levels are reported for senile cataractous lenses.
在酶水平上评估了人晶状体中的山梨醇途径。发现相对于动物晶状体，正常和非糖尿病性以及糖尿病性白内障的成人晶状体中醛糖还原酶（AR）水平有限，而多元醇脱氢酶（PD）水平较高。AR主要局限于晶状体上皮，在幼年晶状体中的含量比成人晶状体高两到三倍。幼年晶状体上皮中的AR水平足以引起显著的渗透应激。AR对葡萄糖的Km约为200 mM，而对NADPH的Km为0.06 mM。NADP对人晶状体AR有非竞争性抑制作用，其Ki相当于NADPH的Km。PD存在于晶状体上皮和皮质中，随着年龄的增长持续保持高水平，并随着皮质受累程度的增加而降低。PD对山梨醇的Km为1.4 mM，对NAD的Km为0.06 mM。NADH（Ki 0.002 mM）在正向反应中竞争性抑制PD。从糖尿病性和非糖尿病性白内障以及正常晶状体中纯化100倍的PD表现出相似的动力学常数。PD在果糖向山梨醇方向具有极高的Vmax。果糖的Km为40 mM，对NADH的Km为0.02 mM。在足够高的浓度下，阿雷司他汀也抑制PD。AR和PD联合产生山梨醇和果糖的活性增加，以及随着年龄增长己糖激酶活性降低，可能是暴露于高葡萄糖应激的人晶状体中糖尿病性白内障形成的原因。报告了老年性白内障晶状体的核苷酸水平。
