Pentose phosphate pathway Cells are provided with a constant supply of NADPH for biosynthesis by the pentose phosphate pathway Also called the hexose monophosphate shunt This pathway also produces ribose-5-P to make RNA, DNA, and coenzyme, ATP, NADH, FADH etc. This pathway consists of two oxidative processes followed by five non-oxidative steps It operates mostly in the cytosol of liver and adipose cells NADPH is used in cytosol for fatty acid synthesis

Oxidative phase produce pentose phosphate and NADPH

Nonoxidative phase recycles pentose phosphate to G-6-P 1.Six five-carbon sugar phosphates are converted to five six-carbon sugar phosphate. 2.Continued recycling leads ultimately to the conversion of glucose 6-phosphate to six carbon dioxide

Transketolase 1.Catalyzes the transfer of a two-carbon fragment from a ketose donor to an aldose acceptor.

Transaldolase 1.Catalyzes the transfer of a three-carbon fragment form a S-7-P to G-3-P for forming F-6-P and E-4-P.

G-6-P is partitioned between glycolysis and the PPP 1. Entry of G-6-P either into glycolysis or into PPP is largely determined by the relative concentrations of NADP+ and NADPH 2. NADP+ >NADPH, NADP+ allosterically stimulate G6PD, thereby increasing the flux of G-6-P through the PPP 3. NADP+ <NADPH, PPP slows and G-6-P is used to fuel glycolysis

LEHNINGER PRINCIPLES OF BIOCHEMISTRY Fifth Edition David L. Nelson and Michael M. Cox © 2008 W. H. Freeman and Company CHAPTER 15 Principles of Metabolic Regulation

Both the amount and the catalytic activity of an enzyme can be regulated 1.Extracellular signal: hormonal, neuronal, growth factors etc. 2.Transcription: activate or repress the transcription 3.The stability of mRNA 4.The rate of translation 5.The rate of protein degradation 6.Sequester the enzyme and its substrate in different compartments 7.By the concentration of substrate 8.The presence of allosteric effector 9.Covalent modification 10.Binding of regulatory protein

Adenine Nucleotides play special Roles in Metabolic regulation 1.It is important to maintain a constant supply and concentration of ATP: [ATP] drop  reaction rate is decreased. 2.AMP concentration is more sensitive indicator of cell’s energetic state than is [ATP] 3.AMP-activated protein kinase - regulated by [AMP] - A reduced nutrient supply or by increase exercise cause the rise in [AMP] - increase glucose uptake, activates glycolysis and fatty acid oxidation - suppress energy requiring processes such as fatty acid, cholesterol, and protein synthesis 4.NADH and NADPH : change in their mass action ratios have global effects on metabolism 5.Glucose

Coordinated Regulation of Glycolysis and Gluconeogensis

Hexokinase 1.Human have four isozyme, encoded by different genes Isozyme: Different proteins that catalyze the same reaction 2.In myocytes, hexokinase II: high affinity for glucose, inhibited by G-6-P 3.In liver, hexokinase IV (glucokinase) - low affinity for glucose: direct regulation by the level of blood glucose - not inhibited by G-6-P - is subjected to inhibition by reversible binding of a regulatory protein specific to liver - are transcriptionally regulated: [ATP] low or [glucose] high