Lady era

By X. Thordir. California State University, Northridge.

Type I collagen [collagen(I)] cheap 100mg lady era pregnancy and caffeine, the most abundant protein in mammals buy discount lady era 100mg line minstrel knight, is a fibrous protein that is the major component of connective tissue. It is found in the extracellular matrix (ECM) of loose connective tissue, bone, tendons, skin, blood vessels, and the cornea of the eye. Collagen(I) contains approximately 33% glycine and 21% proline and hydroxyproline. Hydroxyproline is an amino acid produced by posttranslational modification of peptidyl proline residues (see Chap- ter 7, section V. Procollagen(I), the precursor of collagen(I), is a triple helix composed of three polypeptide (pro- ) chains that are twisted around each other, forming a rope-like structure. Polymerization of collagen(I) molecules forms collagen fibrils, which provide great tensile strength to connective tissues (Fig. The individual polypeptide chains each contain approximately 1,000 amino acid residues. CHAPTER 49 / THE EXTRACELLULAR MATRIX AND CONNECTIVE TISSUE 907 Each turn of the triple helix contains three amino acid residues, such that every third amino acid is in close contact with the other two strands in the center of the struc- ture. Only glycine, which lacks a side chain, can fit in this position, and indeed, every third amino acid residue of collagen is glycine. Thus, collagen is a polymer of (Gly-X-Y) repeats, where Y is frequently proline or hydroxyproline, and X is any other amino acid found in collagen. Procollagen(I) is an example of a protein that undergoes extensive posttransla- The role of carbohydrates in colla- tional modifications. Hydroxylation reactions produce hydroxyproline residues gen structure is still controversial. These reactions The hydroxyproline residues in col- occur after the protein has been synthesized (Fig. Hydroxyproline residues are involved in hydrogen bond forma- the absence of vitamin C (scurvy), the melt- tion that helps to stabilize the triple helix, whereas hydroxylysine residues are the ing temperature of collagen can drop from 42oC to 24oC, because of the loss of inter- sites of attachment of disaccharide moieties (galactose-glucose). These aldehyde residues produce covalent cross-links between collagen molecules (Fig. An allysine residue on one collagen molecule reacts with the amino group of a lysine residue on another molecule, forming a covalent Schiff base that is converted to more stable covalent cross-links. Aldol condensation also may occur between two allysine residues, which forms the structure lysinonorleucine. Types of Collagen At least 19 different types of collagen have been characterized (Table 49. Although each type of collagen is found only in particular locations in the body, more than one type may be present in the ECM at a given location. The various types of collagen can be classified as fibril-forming (types I, II, III, V, and XI), net- work-forming (types IV, VIII and X), those that associate with fibril surfaces (types IX, XII, and XIV), those that are transmembrane proteins (types XIII and XVII), endostatin-forming (types XV and XVIII), and those that form periodic beaded fil- aments (type VI). O O N CH C N CH C prolyl hydroxylase H2 2 + α-Ketoglutarate H2 2 + Succinate C Ascorbate C H O2 CO2 Proline 4-Hydroxyproline residue residue O O N CH C H lysyl hydroxylase 2 + α-Ketoglutarate 2 + Succinate CH Ascorbate CH 2 2 O2 CO2 CH2 CH OH CH2 CH2 +NH +NH 3 3 Lysine 5-Hydroxylysine residue residue Fig. Hydroxylation of proline and lysine residues in collagen. Proline and lysine residues within the collagen chains are hydroxylated by reactions that require vitamin C. Types of Collagen + CH2 CH2 NH3 Collagen Type Gene Structural Details Localization Lysine residue I Col1A1-Col1A2 Fibrils Skin, tendon, bone, cornea II Col2A1 Fibrils Cartilage, vitreous humour III Col3A1 Fibrils Skin, muscle, associates A O2 with type I collagen lysyl oxidase IV Col4A1–Col4A6 Nonfibrillar, mesh collagen All basal laminae (basement NH + OH– membranes) 3 V Col5A1-Col5A3 Small fibers, N-terminal Associates with type I O globular domains collagen in most δ ε ε δ interstitial tissues CH2 C + H2N CH2 CH2 VI Col6A1-Col6A3 Microfibrils, with both N Associates with type I H and C-terminal globular collagen in most Allysine residue Second lysine residue domains interstitial tissues VII Col7A1 An anchoring collagen Epithelial cells; dermal– epidermal junction VIII Col8A1-Col8A2 Nonfibrillar, mesh collagen Cornea, some endothelial B cells H2O IX Col9A1-Col9A3 Fibril-associated collagens Associates with type II with interrupted triple collagen in cartilage and helices (FACIT); vitreous humour δ ε ε δ N-terminal globular CH2 CH N CH2 CH2 domain X Col10A1 Nonfibrillar, mesh collagen, Growth plate, hypertrophic with C-terminal globular and mineralizing cartilage Schiff base domain XI Col11A1-Col11A3 Small fibers Cartilage, vitreous humor O HO XII Col12A1 FACIT Interacts with types I and II δ ε εδ collagen in soft tissues CH2 C + C CH XIII Col13A1 Transmembrane collagen Cell surfaces, epithelial cells H H XIV Col14A1 FACIT Soft tissue Allysine Allysine XV Col15A1 Endostatin-forming collagen Endothelial cells (aldo form) (enol form) XVI Col16A1 Other Ubiquitous XVII Col17A1 Transmembrane collagen Epidermal cell surface XVIII Col18A1 Endostatin-forming Endothelial cells XIX Col19A1 Other Ubiquitous Aldol C condensation See the text for descriptions of the differences in types of collagen. H ε O All collagens contain three polypeptide chains with at least one stretch of triple HO C δ ε δ helix. The non–triple helical domains can be short (such as in the fibril-forming col- CH2 CH CH lagens) or can be rather large, such that the triple helix is actually a minor compo- nent of the overall structure (examples are collagen types XII and XIV). The FACIT (fibril-associated collagens with interrupted triple helices, collagen types IX, XII, H2O and XIV) collagen types associate with fibrillar collagens, without themselves form- ing fibers. The endostatin-forming collagens are cleaved at their C-terminus to form endostatin, an inhibitor of angiogenesis. The network-forming collagens (type IV) H ε O C form a mesh-like structure, because of large (approximately 230 amino acids) non- δ ε δ collagenous domains at the carboxy-terminal (Fig. And finally, a number of CH2 CH C collagen types are actually transmembrane proteins (XIII and XVII) found on epithe- lial or epidermal cell surfaces, which play a role in a number of cellular processes, Lysinonorleucine including adhesion of components of the ECM to cells embedded within it. Formation of cross-links in colla- Types I, II, and III collagens form fibrils that assemble into large insoluble fibers.

An alcoholic is brought to the Emergency Room for a hypoglycemic coma buy lady era 100 mg otc menstrual 5 days early. Because alcoholics are frequently malnourished best 100 mg lady era womens health 7 day eating plan, which of the following enzymes can be used to test for a thiamine deficiency? Intravenous fructose feeding can lead to lactic acidosis caused by which of the following? The polyol pathway of sorbitol production and the HMP shunt pathway are linked by which of the following? The pathways for oxidation of fatty acids, Krebs first formulated its reactions glucose, amino acids, acetate, and ketone bodies all generate acetyl CoA, into a cycle. It is also called the “citric acid which is the substrate for the TCA cycle. As the activated 2-carbon acetyl cycle” because citrate was one of the first group is oxidized to two molecules of CO2, energy is conserved as NADH, compounds known to participate. The most common name for this pathway, the tricar- FAD(2H), and GTP (Fig. NADH and FAD(2H) subsequently donate boxylic acid or TCA cycle, denotes the electrons to O2 via the electron transport chain, with the generation of ATP involvement of the tricarboxylates citrate from oxidative phosphorylation. Thus, the TCA cycle is central to energy gen- and isocitrate. Within the TCA cycle, the oxidative decarboxylation of -ketoglutarate is cat- The major pathways of fuel oxida- alyzed by the multisubunit -ketoglutarate dehydrogenase complex, which con- tion generate acetyl CoA, which is tains the coenzymes thiamine-pyrophosphate, lipoate, and FAD. In plex, the pyruvate dehydrogenase complex (PDC), catalyzes the oxidation of the first step of the TCA cycle, the acetyl por- pyruvate to acetyl CoA, thereby providing a link between the pathways of glycoly- tion of acetyl CoA combines with the 4- sis and the TCA cycle (see Fig. In the next two oxidative transferred to NAD and FAD and also the carbon in the two CO2 molecules that decarboxylation reactions, electrons are are produced. Oxaloacetate is used and regenerated in each turn of the cycle (see transferred to NAD to form NADH, and 2 Fig. However, when cells use intermediates of the TCA cycle for molecules of electron-depleted CO2 are released. Subsequently, a high- energy phosphate bond in GTP is generated from Glucose Fatty acids substrate level phosphorylation. In the Pyruvate remaining portion of the TCA cycle, succi- Ketone bodies nate is oxidized to oxaloacetate with the generation of one FAD(2H) and one NADH. CO2 The net reaction of the TCA cycle, which is the sum of the equations for individual Acetate Acetyl CoA Amino acids steps, shows that the two carbons of the CoASH acetyl group have been oxidized to two mol- OxaloacetateOxaloacetate + (4c)(4c) ecules of CO2, with conservation of energy NADH + H Citrate (6c)Citrate (6c) as three molecules of NADH, one of Malate (4c)Malate (4c) Isocitrate (6c)Isocitrate (6c) FAD(2H), and one of GTP. Fumarate (4c)Fumarate (4c) Tricarboxylic acid NADH + H+ FAD (2H) (TCA) cycle Succinate (4c)Succinate (4c) CO 2 αα-Ketoglutarate (5c)-Ketoglutarate (5c) GTP Succinyl-Succinyl- NADH + H+ GDP CoACoA (4c) CO2 Net reaction Acetyl CoA + 3NAD+ + FAD 2CO + CoASH + 3NADH + 3H+ 2 + GDP + P + 2Hi 2O + FAD (2H) + GTP Fig. The TCA cycle occurs in the mitochondrion, where its flux is tightly coordi- nated with the rate of the electron transport chain and oxidative phosphorylation through feedback regulation that reflects the demand for ATP. The rate of the TCA cycle is increased when ATP utilization in the cell is increased through the response of several enzymes to ADP levels, the NADH/ NAD ratio, the rate of FAD(2H) oxidation or the Ca2 concentration. For example, isocitrate dehydro- genase is allosterically activated by ADP. There are two general consequences to impaired functioning of the TCA cycle: (1) an inability to generate ATP from fuel oxidation, and (2) an accumulation of TCA cycle precursors. For example, inhibition of pyruvate oxidation in the TCA cycle results in its reduction to lactate, which can cause a lactic acidosis. The most common situation leading to an impaired function of the TCA cycle is a rela- tive lack of oxygen to accept electrons in the electron transport chain. THE WAITING ROOM Otto Shape, a 26-year-old medical student, has faithfully followed his diet and aerobic exercise program of daily tennis and jogging (see Chapter 19). He has lost a total of 33 lb and is just 23 lb from his college weight of 154 lb. His exercise capacity has markedly improved; he can run for a longer time at a Vitamins and minerals faster pace before noting shortness of breath or palpitations of his heart. Even his required for the TCA cycle test scores in his medical school classes have improved. In Riboflavin (FAD) addition to a low body weight, decreased muscle mass, glycogen, and fat Pantothenate (CoA) stores, she has iron-deficiency anemia (see Chapter 16). She has started to Thiamine gain weight, and is trying a daily exercise program.

Autopsies of patients with Alzheimer’s disease show protein aggregates called neurofibrillary tangles and neuritic plaques in various regions of the brain generic 100mg lady era overnight delivery women's health clinic indooroopilly. These plaques exhibit the characteristic staining of amyloid proven 100 mg lady era pregnancy costumes. Which of the following struc- tural features is the most likely characteristic of at least one protein in these plaques? While studying a novel pathway in a remote species of bacteria, you discover a new globular protein that phosphorylates a sub- strate, using ATP as the phosphate donor. This protein most likely contains which of the following structures? Enzyme catalysts bind reactants (substrates), con- in the absence of enzyme vert them to products, and release the products. Although enzymes may be modi- fied during their participation in this reaction sequence, they return to their origi- nal form at the end. In addition to increasing the speed of reactions, enzymes provide a means for regulating the rate of metabolic pathways in the body. This 8 ft chapter describes the properties of enzymes that allow them to function as cata- lysts. The next chapter explains the mechanisms of enzyme regulation. An enzyme binds the substrates of the reaction and con- verts them to products. The substrates are bound to specific substrate binding sites on the enzyme through interactions with the amino acid residues of the enzyme. The spatial geometry required for all the interactions between the sub- strate and the enzyme makes each enzyme selective for its substrates and ensures that only specific products are formed. The substrate binding sites overlap in the active catalytic After one second site of the enzyme, the region of the enzyme where the reaction occurs. Within the with one molecule of enzyme catalytic site, functional groups provided by coenzymes, tightly bound metals, and, of course, amino acid residues of the enzyme, participate in catalysis. The functional groups in the cat- alytic site of the enzyme activate the substrates and decrease the energy needed to 8 ft form the high-energy intermediate stage of the reaction known as the transition state complex. Some of the catalytic strategies employed by enzymes, such as gen- eral acid-base catalysis, formation of covalent intermediates, and stabilization of the transition state, are illustrated by chymotrypsin. Enzymes have a functional pH range determined by the pKas of functional groups in the active site and the interactions required for three-dimensional structure. Non-denaturing increases of temperature increase the Fig. The effectiveness of many drugs and toxins 11 tion by a factor of 10 or higher. To appreciate depends on their ability to inhibit an enzyme. The strongest inhibitors are covalent an increase in reaction rate by this order of inhibitors, compounds that form covalent bonds with a reactive group in the magnitude, consider a room-sized box of golf enzyme active site, or transition state analogues that mimic the transition state balls that “react” by releasing energy and turn- complex. If the rate of the reaction in a common name and a systematic classification that includes a name and an the absence of enzyme were 100 golf balls per Enzyme Commission (EC) number. Some of the effects of alcohol ingestion, such as A year after recovering from salicylate poisoning (see Chapter 4), Dennis the psychotropic effects on the brain or inhi- “the Menace” Veere was playing in his grandfather’s basement. Dennis bition of vitamin transport, are direct effects drank an unknown amount of the insecticide malathion, which is some- caused by ethanol itself. However, many of times used for killing fruit flies and other insects (Fig. Sometime later when the acute and chronic pathophysiologic he was not feeling well, Dennis told his grandfather what he had done. Veere effects of alcohol relate to the pathways of retrieved the bottle and rushed Dennis to the emergency room of the local hospital.

Then order lady era 100 mg otc breast cancer 1749, a fracture of the lateral cortex is produced with correction of the valgus deformity purchase 100mg lady era visa menstruation flow, and the osteotomy is stabilized with a K-wire (Figure S5. There is overlapping of the plantar medial joint capsule to align the sesamoids under the distal end of the first metatarsal (Figure S5. The first metatarsal joint is now aligned to neutral, and the distal- based flap is sutured back to the metatarsal to maintain this correc- tion (Figure S5. All the wounds are closed and a soft dressing is applied, with a bulky dressing between the first and second metatarsal. Usually, a short-leg cast is applied because this procedure almost al- ways is performed in combination with hindfoot correction. A small wrap is placed around the great toe to hold it in correct alignment. Immobilization is required for 4 to 6 weeks until the osteotomies have healed. Postoperative orthotic use usually is not indicated. If the articular surface has severe degenerative changes, or if the child is a nonambulator, a metatarsal phalangeal joint fusion is indicated. Cartilage should be removed utilizing an oscillating saw and resect- ing only the distal half of the articular surface of the first metatarsal. This cartilage should be transected in a plane that will be vertical with the foot, usually with a 15° to 20° dorsal angulation to the longitudinal axis of the metatarsal. This distal phalanx then has its cartilage and surface resected par- allel to the distal phalanx. The two flat surfaces now will meet with the toe being in approximately 15° to 20° of dorsiflexion rel- ative to the longitudinal axis of the metatarsal. Additional dorsi- flexion at the first metatarsal phalangeal joint is indicated if there is any weight bearing on the proximal phalanx with the foot in neutral position. If this is a fully adult-sized patient, the ideal fixation is performed by using a 6. This screw provides excellent fixation but only works in an adult- sized foot (Figure S5. The hole for this screw is drilled retro- grade from the middle of the distal end of the metatarsal. The hole in the metatarsal is also tapped retrograde. A hole in the middle of the phalanx is opened with the drill, but tapping in not usually required. The other option for fixation is to use crossed K-wires or to use a four-hole plate on the dorsum of the metatarsal phalangeal joint. After the cast is re- moved, full activity is allowed as tolerated. Correction of Clawed Toes Indication Correction of claw toes in children with CP is only required if the toes are having nail problems from chronic pressure or are painful in shoes. If contracted flexor tendons are present with the clawed toes demon- strating flexion of the metatarsal phalangeal joint and interphalangeal joints, a direct plantar tenotomy with a number 11 knife is used, and the flexor tendons are cut just distal to the metatarsal phalangeal joint (Figure 5. This cut should allow full correction of the toes, and if any contrac- tures still are present in the joints, the correction can be fixed with K-wires crossing the interphalangeal joints and extended into the metatarsal joint if needed. Only 2 to 3 weeks of fixation with K-wires is necessary. If the clawed toes are cocked up with extension of the first metatarsal phalangeal joint and flexion of the interphalangeal joint, resection of the proximal interphalangeal joint usually is required. This resection is made through a middorsal incision with the joint being resected uti- lizing a rongeur. Then, the toes are corrected and fixed with K-wires for approximately 4 weeks (Figure S5. Postoperative Care No cast immobilization is needed. Medial Border Great Toenail Resection Indication This procedure is indicated if there have been repeat inflammations with an ingrown toenail.