Ординатура / Офтальмология / Английские материалы / Biochemistry of the Eye 2nd edition_Whikehart_2003

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Library of Congress Cataloging-in-Publication Data

Whikehart, David R.

Biochemistry of the eye/David R. Whikehart.–2nd ed. p. ; cm.

Includes bibliographical references and index. ISBN 0-7506-7152-1

1. Eye–Metabolism. 2. Eye–Physiology. I. Title.

[DNLM: 1. Eye–chemistry. 2. Eye–physiopathology. WW 101 W561b 2003]

QP475 .W48 2003 612.8′4–dc21

2002026298

Publishing Director: Linda Duncan

Managing Editor: Christie M. Hart

Project Manager: Mary B. Stermel

Printed in USA

Last digit is the print number: 9 8 7 6 5 4 3 2 1

Color Plate 1

One of several proposed structures for

α-crystallin. The model shows bound rings of crystallin subunits laid on top of each other. The large subunit spheres are hydrophilic C-terminal domains while the small subunit spheres are hydrophobic N-terminal domains. Extending from the C-terminal domains are C-terminal peptide extensions that cover the central cavity where chaperone activity may take place. (Redrawn from Carver JA, Aquilina JA, and Truscott RJW: A possible chaperone-like quaternary structure for a-crystallin. Exp Eye Res 59: 231–234, 1994.)

C

cytosol

Glu #129, the site of attachment for the Schiff base 129 counterion

Color Plate 2

Diagram of a red or green cone pigment protein inserted into a cone membrane showing the site of attachment of the Schiff base counter ion and covalent attachment for the 11-cis retinal. Also illustrated are shifts in color vision produced by a substitution of certain amino acids (e.g., Thr for Ala to produce a shift of 18 nm). (The figure was redrawn from Nathans J: The evolution and physiology of human color vision: insights from molecular genetic studies of visual pigments, Neuron 24:299–312, 1999.)

PANCREAS

ISLET

A or α cell (glucagon)

B or β cell (insulin)

D or δ cell (somatostatin)

Color Plate 3

Diagram of islet cells in the human pancreas. Essentially, three types of cells produce insulin (β cells), glucagon (α cells), and somatostatin (δ cells). A fourth type of cell (F) produces pancreatic polypeptide. All cell types secrete hormones that deal with carbohydrate (and other intermediate) metabolic control. (Based on a drawing in Williams G, Pickup JC: Handbook of diabetes, ed 2, Oxford, 1999, Blackwell Science; 27.)

capillary all-trans RETINOL (t)

Color Plate 4

The processing and transport of vitamin A at PE (pigment epithelial) cells and photoreceptor outer segments. At PE cells retinol may be stored as an ester or transported to the outer segment. The transport between and within PE cells and photoreceptor outer segments of 11-cis retinal as well as between photoreceptor cells and PE cells of all-trans retinol makes use of other transport binding proteins (t), an interstitial retinol binding protein (IRBP) as well as an intracellular retinal binding protein (CRBP) as described by Hollyfield et al (1985). Metabolic transformations of the different vitamin A forms are enzymatically catalyzed (*) in both the PE and photoreceptor cells. See text for further explanations.

M

G2

Checkpoints

Go

S

G1

Color Plate 6

The cell cycle and some of the many biochemical pathways that influence it. A diagram of the cell cycle is shown in the upper part of the figure. In the resting stage, G1 or gap one, no synthetic processes leading to cell division occur. A subdivision of the G1 phase, known as Go also occurs in which the cell cannot enter into a synthetic process leading to cell division. Cells may be in Go, for example, when there is insufficient nourishment to begin DNA synthesis. In the S or synthesis phase, synthesis of new DNA (replication) occurs prior to cell division. The G2 phase (gap two), is an interphase prior to mitosis or cell division. In this phase there are four sets of chromosomes present. In mitosis (the M phase), the complex process of cell division occurs (see, for example, Lodish et al, 2000). The movement or commitment of a cell into its next phase occurs by passage through so called “checkpoints” or “restriction points,” which are determined by a variety of biochemical mechanisms. The lower part of the Figure illustrates one phase commitment mechanism for passage though the checkpoint from the G1 to the S phase. Such a mechanism involves the proteins E2F and Rb (right). When E2F and Rb are bound together, the cell is held at the G1 phase. When the Rb protein is phosphorylated by cyclin dependent kinase 4 (when cyclin D is bound to the kinase) the Rb and E2F proteins are released from each other and both promote checkpoint passage by the stimulation of mRNAs to make proteins necessary for the S phase of the cell cycle. Obviously any influence on the activity of the cyclin D/CDK4 complex will influence the ability of the cell to divide (i.e., to enter the S phase). Three proteins (of many such as KIP [kinase inhibitor proteins]) that are known to influence this complex are p53, p63, and p73. These proteins cause the synthesis of mRNA for p21 a protein that inhibits the cyclin D/CDK4 enzyme complex. Any defect in p53, for example, may allow the cyclinD/CDK4 enzyme complex to carry out unchecked catalysis to separate E2F and Rb at a high rate and allow uncontrolled cell division. This, in fact, occurs in some cancer cells in which p53 occurs in mutated and useless forms.