Pathway: Keratan sulfate degradation
Reactions in pathway: Keratan sulfate degradation :
Keratan sulfate degradation
Keratan sulfate proteoglycans (KSPGs) are degraded in lysosomes as part of normal homeostasis of glycoproteins. Glycoproteins must be completely degraded to avoid undigested fragments building up and causing a variety of lysosomal storage diseases. KSPGs are Asn-linked glycoproteins and are acted upon by exo-glycosidases to release sugar monomers. The main steps of degradation are shown representing the types of cleavage reactions that occur so the full degradation of KS is not shown to avoid repetition. The proteolysis of the core protein of the glycoprotein is not shown here (Winchester 2005, Aronson & Kuranda 1989).
Starches and sugars are major constituents of the human diet and the catabolism of monosaccharides, notably glucose, derived from them is an essential part of human energy metabolism (Dashty 2013). Glucose can be catabolized to pyruvate (glycolysis) and pyruvate synthesized from diverse sources can be metabolized to form glucose (gluconeogenesis). Glucose can be polymerized to form glycogen under conditions of glucose excess (glycogen synthesis), and glycogen can be broken down to glucose in response to stress or starvation (glycogenolysis). Other monosaccharides prominent in the diet, fructose and galactose, can be converted to glucose. The disaccharide lactose, the major carbohydrate in breast milk, is synthesized in the lactating mammary gland. The pentose phosphate pathway allows the synthesis of diverse monosaccharides from glucose including the pentose ribose-5-phosphate and the regulatory molecule xylulose-5-phosphate, as well as the generation of reducing equivalents for biosynthetic processes. Glycosaminoglycan metabolism and xylulose-5-phosphate synthesis from glucuronate are also annotated as parts of carbohydrate metabolism.
The digestion of dietary starch and sugars and the uptake of the resulting monosaccharides into the circulation from the small intestine are annotated as parts of the “Digestion and absorption” pathway.
Metabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as the inactivation and elimination of toxic ones generated endogenously or present in the extracellular environment. The processes of energy metabolism can be classified into two groups according to whether they involve carbohydrate-derived or lipid-derived molecules, and within each group it is useful to distinguish processes that mediate the breakdown and oxidation of these molecules to yield energy from ones that mediate their synthesis and storage as internal energy reserves. Synthetic reactions are conveniently grouped by the chemical nature of the end products, such as nucleotides, amino acids and related molecules, and porphyrins. Detoxification reactions (biological oxidations) are likewise conveniently classified by the chemical nature of the toxin.
At the same time, all of these processes are tightly integrated. Intermediates in reactions of energy generation are starting materials for biosyntheses of amino acids and other compounds, broad-specificity oxidoreductase enzymes can be involved in both detoxification reactions and biosyntheses, and hormone-mediated signaling processes function to coordinate the operation of energy-generating and energy-storing reactions and to couple these to other biosynthetic processes.