Carbohydrate Metabolism
Lara Wijayasiri, Kate McCombe, Paul Hatton, David Bogod in The Primary FRCA Structured Oral Examination Study Guide 1, 2017
To enter the Krebs cycle, pyruvate is transported into the mitochondria where it is converted into the 2-carbon molecule, acetyl coenzyme A (acetyl CoA) by pyruvate dehydrogenase. Acetyl CoA enters the Krebs cycle by being bound to the 4-carbon molecule oxaloacetate to form the 6-carbon molecule, citrate. This molecule is then broken down again to a 5-carbon molecule and again to back to oxaloacetate and so on (hence the cycle…). During this cycle, molecules that are high in energy are generated and each turn of the cycle yields: 1 ATP3 NADH (nicotinamide adenine dinucleotide. NAD+ is a coenzyme that acts as an electron acceptor to create NADH)1 FADH2 (flavin adenine dinucleotide is a redox cofactor, i.e. it undergoes reduction-oxidation)
Anatomy, Biochemistry and Physiology
Massimo Maffei in Vetiveria, 2002
The primary carboxylation reaction, common to all three variants, occurs in the cytosol of the mesophyll cells and is catalysed by phosphoenolpyruvate carboxylase (PEP-case), using HCO3− rather than CO2 as a substrate. The fate of the oxaloacetate produced in this reaction depends on the C4 variant (Gutierrez et al., 1974). In the NADP-ME type, oxaloacetate is reduced to malate in the mesophyll chloroplasts, then transported to the bundle sheath cell chloroplasts and decarboxylated by NADP-ME enzyme. In the NAD-ME and PCK species, oxaloacetate undergoes transamination in the cytosol with glutamate as amino donor. The aspartate is transported into the bundle sheath cells and reconverted to oxaloacetate by transamination in the mitochondria (NAD-ME species) or the cytosol (PCK species). Without changing compartmentalization, the oxaloacetate is reduced and then decarboxylated by NAD-ME in NAD-ME species, while in PCK species oxaloacetate is decarboxylated by PCK. In NADP-ME plants, the C3 acid transported back to the mesophyll is pyruvic acid as pyruvate but in NAD-ME and PCK species alanine is probably converted to pyruvate in the mesophyll cell cytosol. The final reaction of the C4 pathway, which is common to all three variants, is the conversion of pyruvate to phosphoenolpyruvate within the mesophyll chloroplasts (Maffei, 1999).
Pyruvate carboxylase deficiency
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop in Atlas of Inherited Metabolic Diseases, 2020
The complex biochemical picture reminiscent of a defect in the urea cycle appears to result from depletion of intracellular oxaloacetate and aspartate [22, 23, 27]. Aspartate is a source of the second nitrogen of urea (Figure 48.1); its deficiency would lead to citrullinemia and hyperammonemia. Aspartate is also involved in the shuttle of reducing equivalents from cytosol to mitochondria [46] by which the NAD+/NADH ratio (nicotinamide adenine dinucleotide/reduced nicotinamide adenine dinucleotide) is very oxidized in the cytosol and reduced in mitochondria; its lack would make the cytosol more reduced and the mitochondria more oxidized, as occurs in this phenotype.
BCG-induced trained immunity in macrophage: reprograming of glucose metabolism
Published in International Reviews of Immunology, 2020
Yuntong Liu, Shu Liang, Ru Ding, Yuyang Hou, Feier Deng, Xiaohui Ma, Tiantian Song, Dongmei Yan
Pyruvate is converted to acetyl-CoA in mitochondria by PDH, then condenses with oxaloacetic acid and enter into TCA cycle to produce citrate. In addition, cells utilize acetyl-CoA, rather than pyruvate, to generate NAD+ in order to inhibit OXPHOS and promote aerobic glycolysis.76 Glutamine metabolism provides the source for LPS-induced increase in succinate generation, via anaplerosis proceeding through α-ketoglutarate (α-KG), as well as via the γ-aminobutyric acid (GABA) shunt.47 Citrate has been shown to be an inflammatory signal, leading to the production of three key pro-inflammatory mediators: NO, ROS and prostaglandins (PGs). Citrate is transported to the cytoplasm and exchange with malate through citrate carrier (CIC). In the cytoplasm, citrate acts as a key regulator of energy metabolism, inhibiting glycolysis and TCA cycle while promoting lipid synthesis and glycosynthesis. It produces oxaloacetic acid and acetyl-CoA. Acetyl-CoA is used for the biosynthesis of fatty acids, and oxanoacetic acid can produce NADPH by generating malate and pyruvate.84 It is known that NADPH participates in NO and ROS production. Studies have shown that long-term activated monocytes in the absence of glucose can enhance their transport activity by acetylating CIC, promoting citrate efflux and maintaining NADPH, which is inadequate supplied by PPP. This process is accompanied by the depletion of malate and the conversion of citrate into glutamate,85 so whether this process can explain the accumulation of glutamate and malate induced by BCG remains to be further studied.
Is air pollution a potential cause of neuronal injury?
Published in Neurological Research, 2019
Yu Ji, Christopher Stone, Longfei Guan, Changya Peng, Wei Han
As it occurs in the periphery, the purpose of gluconeogenesis may be described generally as, along with glycogenolysis, the maintenance of energy homeostasis through the generation of glucose for use by extrahepatic tissues during prolonged fasts, a task it achieves through de novo synthesis of glucose from precursors such as glycerol, amino acids, pyruvate, and lactate [31]. Accomplishing this requires the coordinated function of a series of enzyme-catalyzed reactions, most of which are also involved in glycolysis, and simply run in reverse while serving the anabolic purpose of gluconeogenesis. In addition to these reversible steps, however, gluconeogenesis possesses several unique, irreversible enzymes that serve as important regulatory checkpoints in the coordination of cellular energy metabolism with overall organismal energy homeostasis: pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), fructose 1,6-bisphosphatase (FBP), and glucose 6-phosphatase (G6PC) [32]. PC catalyzes the ATP-intensive first of these regulatory reactions within mitochondria by carboxylating pyruvate to yield oxaloacetate. Oxaloacetate is subsequently decarboxylated, shuttled out of the mitochondrion, and then phosphorylated by PEPCK in a reaction that requires GTP. After an intervening sequence of reversed glycolysis reactions that generates fructose 1,6-bisphosphate, FBP yields fructose 6-phosphate, which is isomerized to glucose 6-phosphate and, finally, dephosphorylated to yield glucose de novo; these latter two dephosphorylations both require ATP.
Aberrant lipid metabolism as a therapeutic target in liver cancer
Published in Expert Opinion on Therapeutic Targets, 2019
Evans D. Pope, Erinmarie O. Kimbrough, Lalitha Padmanabha Vemireddy, Phani Keerthi Surapaneni, John A. Copland, Kabir Mody
De novo fatty acid (FA) synthesis occurs in high energy or fed states. During FA synthesis, glucose is taken up in the liver where it is then converted to FAs for storage in the form of triacylglycerols (TAGs) [8]. The initial step in FA synthesis is glycolysis. Glycolysis results in the production of pyruvate from glucose [8]. This reaction takes place in the cytosol of the hepatocyte. After pyruvate has been produced, pyruvate enters into the mitochondria and is converted to citrate via the citric acid (TCA) cycle [9]. Once citrate has been formed, citrate is expelled out of the mitochondria via the citrate shuttle. Citrate is converted into oxaloacetate and acetyl CoA via ATP-citrate lyase (ACL) [9]. The oxaloacetate is further broken down into pyruvate and NADPH. The acetyl CoA and NADPH are then used for FA synthesis [9]. Acetyl CoA is converted to Malonyl CoA via ACC [10]. Malonyl CoA and Acetyl CoA are combined using FASN to help form saturated fatty acids (SFA) (palmitoyl-CoA and stearoyl-CoA) [10]. Critically, these are then converted to monounsaturated fatty acids (MUFA) palmitoleoyl-CoA and oleoyl-CoA by SCD [11]. MUFAs are critical as building blocks for membrane synthesis, prostaglandin synthesis, and as the source for TAGs. They are important to cancer cell survival via their role in the induction of autophagy, enhancement of cell membrane turnover, effecting intracellular signaling and gene transcription, and increasing energy production.
Related Knowledge Centers
- Amino Acid Synthesis
- Enol
- Fatty Acid Synthesis
- Glyoxylate Cycle
- Organic Compound
- Urea Cycle
- Citric Acid Cycle
- Gluconeogenesis
- Chemical Formula
- Conjugate