Pyruvate cell transport

After PEP carboxylase makes the oxaloacetate, it is transported to the bundle sheath cells. First, NADPH reduces it to malate, and it is then transported to the bundle sheath cells. In the bundle sheath cells, malic enzyme cleaves the malate to pyruvate and C02 for Rubisco. This generates NADPH as well, so the C4 cycle consumes no reducing equivalents. Pyruvate is transported from the bundle sheath back to the mesophyll cells where it is rephosphorylated to phosphoenolpyruvate, expending the equivalent of two ATP high-energy phosphates. ... 

In anaerobic conditions, cells can metabolize pyruvate to lactate or to ethanol plus CO2 (in the case of yeast), with the reoxidation of NADH. In aerobic conditions, pyruvate is transported into the mitochondrion, where pyruvate dehydrogenase converts it into acetyl CoA and CO2 (see Figure 8-5). 

Pyruvate, citrate, a-ketoglutarate and malate, ADP, ATP, and phosphate (as well as many other compounds) have specific transporters in the inner mitochondrial membrane that transport compounds between the mitochondrial matrix and cytosol in exchange for a compound of similar charge. In contrast, CoASH, acetyl CoA, other CoA derivatives, NAD and NADH, and oxaloacetate, are not transported at a metabolically significant rate. To obtain cytosolic acetyl CoA, many cells transport citrate to the cytosol, where it is cleaved to acetyl CoA and oxaloacetate by citrate lyase. 

FIGURE 20.1 Pyruvate produced hi glycolysis is oxidized in the tricarboxylic acid (TCA) cycle. Electrons liberated in this oxidation flow through the electron transport chain and drive the synthesis of ATP in oxidative phosphorylation. In eukaryotic cells, this overall process occurs in mitochondria. 

Insulin stimulates lipogenesis by several other mechanisms as well as by increasing acetyl-CoA carboxylase activity. It increases the transport of glucose into the cell (eg, in adipose tissue), increasing the availability of both pyruvate for fatty acid synthesis and glycerol 3-phosphate for esterification of the newly formed fatty acids, and also converts the inactive form of pyruvate dehydrogenase to the active form in adipose tissue but not in liver. Insulin also—by its ability to depress the level of intracellular cAMP—inhibits lipolysis in adipose tissue and thereby reduces the concentration of... 

A problem for gluconeogenesis is that pyruvate carboxylase, which produces oxaloacetate from pyravate, is present in the mitochondria but phosphoenolpyruvate carboxylase, at least in human liver, is present in the cytosol. For reasons given in Chapter 9, oxaloacetate cannot cross the mitochondrial membrane and so a transporter is not present in any cells. Hence, oxaloacetate is converted to phosphoenolpyruvate which is transported across the membrane (Figure 6.25). 

The transport of amino acids at the BBB differs depending on their chemical class and the dual function of some amino acids as nutrients and neurotransmitters. Essential large neutral amino acids are shuttled into the brain by facilitated transport via the large neutral amino acid transporter (LAT) system [29] and display rapid equilibration between plasma and brain concentrations on a minute time scale. The LAT-system at the BBB shows a much lower Km for its substrates compared to the analogous L-system of peripheral tissues and its mRNA is highly expressed in brain endothelial cells (100-fold abundance compared to other tissues). Cationic amino acids are taken up into the brain by a different facilitative transporter, designated as the y system, which is present on the luminal and abluminal endothelial membrane. In contrast, active Na -dependent transporters for small neutral amino acids (A-system ASC-system) and cationic amino acids (B° system), appear to be confined to the abluminal surface and may be involved in removal of amino acids from brain extracellular fluid [30]. Carrier-mediated BBB transport includes monocarboxylic acids (pyruvate), amines (choline), nucleosides (adenosine), purine bases (adenine), panthotenate, thiamine, and thyroid hormones (T3), with a representative substrate given in parentheses [31]. 

The processes involved in neurochemical transmission in a cholinergic neuron are shown in Figure 9.2. The initial substrates for the synthesis of acetylcholine are glucose and choline. Glucose enters the neuron by means of facilitated transport. There is some disagreement as to whether choline enters cells by active or facilitated transport. Pyruvate derived from glucose is transported into mitochondria and converted to acetylcoenzyme A (acetyl-CoA). The acetyl-CoA is transported back into the cytosol. With the aid of the enzyme choline acetyl-transferase, acetylcholine is synthesized from acetyl-CoA and choline. The acetylcholine is then transported into and stored within the storage vesicles by as yet unknown mechanisms. 

Under aerobic conditions, the glycolytic pathway becomes the initial phase of glucose catabolism (fig. 13.2). The other three components of respiratory metabolism are the tricarboxylic acid (TCA) cycle, which is responsible for further oxidation of pyruvate, the electron-transport chain, which is required for the reoxidation of coenzyme molecules at the expense of molecular oxygen, and the oxidative phosphorylation of ADP to ATP, which is driven by a proton gradient generated in the process of electron transport. Overall, this leads to the potential formation of approximately 30 molecules of ATP per molecule of glucose in the typical eukaryotic cell. 

Whereas a major function of biological membranes is to maintain the status quo by preventing loss of vital materials and entry of harmful substances, membranes must also engage in selective transport processes. Living cells depend on an influx of phosphate and other ions, and of nutrients such as carbohydrates and amino acids. They extrude certain ions, such as Na+, and rid themselves of metabolic end products. How do these ionic or polar species traverse the phospholipid bilayer of the plasma membrane How do pyruvate, malate, the tricarboxylic acid citrate and even ATP move between the cytosol and the mitochondrial matrix (see figs. 13.15 and 14.1) The answer is that biological membranes contain proteins that act as specific transporters, or permeases. These proteins behave much like conventional enzymes They bind substrates and they release products. Their primary function, however, is not to catalyze chemical reactions but to move materials from one side of a membrane to the other. In this section we discuss the general features of membrane transport and examine the structures and activities of several transport proteins. 

---