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A chemical signal to cAMP is recognized by or 2 adrenergic receptors that are characterized by what 3 things?

Anabolic pathways make complex molecules *(ie proteins) from small molecules (ie amino acids). This requires energy which is usually provide by what source?

1. Extracellular ligand-bind region 2. 7 Transmembrane Helices 3. Intracellular domain that interacts w/G proteins

Break down of ATP to ADP and Pi. Also REDUCTIONS in which reducing power is provided by electron DONOR NADPH
3 Stages - Stage 1. Hydrolysis of complex molecules to simple molecules (buildig blocks) Stage 2. Conversion of build blocks to Acetyl CoA (& other simple intermediates) Stage 3. Oxidation of Acetyl CoA; oxidative phosphorylation

Catabolism involves how many stages?

Catabolism involves what molecules?

Proteins, Polysaccharides and Lipids broken down to amino acids, monosaccharides, glycerol and fatty acids cAMP Phosphodiesterase - cleaves the cyclic 3',5'-phosphodiester bond.

Deactivation of cAMP - rapid hydrolyzation of cAMP to 5'-AMP is done by what enzyme?


During fasting, Elevated levels of glucagon and Low levels of insulin, intracellular levels of hepatic fructose 2,6BP decreases the rate of glycolysis and increases the rate of what other pathway?

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F2,6 Biphosphate is formed from Fructose 6P using what enzyme?

Phosphofructokinase 2 (PFK-2) - part of a BIFUNCTIONAL Enzyme w/FBP-2

Fructose 2, 6 Biphosphate activates PFK-1, it acts as an inhibitor of what enzyme?

Fructose 1, 6 Bisphophatase - enzyme needed in gluconeogenesis

Glucose enzyme in liver PARENCHYMAL cells and islet cells of the pancrease that phosphorylates hexoses during hyPERglycemia? (Most predominant enzyme responsible for phosphorylation of glucose)

Glucokinase - high Km (low affinity) most active at a high concentration of glucose & high Vmax = efficient removal of glucose from portal blood to prevent large amount of glucose from entering the systemic circulation (after carbohydrate rich meal)

Glucose enzyme in most tissues that phosphorylates hexoses?

Hexokinase - low Km (high affinity) w/low Vmax. Phosphorylates and metabolizes glucose even when concentration of glucose is low. Low Vmax keeps it from phosphorylating more sugar than the cell can use

How are phosphate groups added to proteins by protein kinases removed?

Removed by protein phosphatases enzymes that hydrolytically cleave phosphate esters Facilitated diffusion (Glut transporters, 114) or Na+-monosaccharide co-transport

How does glucose get into the cells?

Insulin promotes the transcription of the glucokinase gene, resulting in an increase in liver enzyme protein and a increase in total glucokinase activity, what is the effect of this process in a diabetic?

Absence of insulin in patients w/diabetes causes a deficiency in Hepatic glucokinase, therefore, this contributes to an inability of the patient to efficiently decrease blood glucose levels

Intracellular signal that indicates glucose is abundant?

F 2,6 BP - usually d/t decreased levels of glucagon and increased insulin (following a meal)
1. Availability of substrates 2. Product inhibition 3. Change in level of Allosteric Activators 4. Change in level of Allosteric Inhbitors

Intracellular signals - RAPID RESPONSE (continuous regulation inside the cell) - influence the rate of a metabolic pathway. What signals are these?

Metabolism is also regulated by intercellular signals SLOW RESPONSE - (regulation from outside the cell). How do cells communicate cell to cell?

1. Surface to Surface contact or Gap junctions (direct communication b/w cytoplasms of adjacent cells) Hormones, neurotransmitters and availability of nutrients (these influence signals generated inside the cell) Adenylyl Cyclase

Metabolism is regulated by intracellular signals and intercellular signals, how are individual cells informed of he metabolic state of the body as a whole?
Metabolism is regulated by intracellular signals, intercellular signals, second messengers and a 4th mechanism which is a membrane bound enzyme that converts ATP to 3'5'-adenosine monophosphate (cAMP).

Most important control point in Glycolysis (Rate limiting step)?

PFK-1

Pathways are catabolic (degrade) or anabolic (synthesize). What is the purpose of catabolism?

Capture energy (ATP) from degradation of energy rich molecules

PFK-2/FBP-2 Complex is a bifunctional enzyme, when phosphorylated which part is active and which part in inactive? Phosphodiesterase can be inhibited by what drugs?

Phosphorylated - FBP-2 is active so, PFK-2 is inactive Dephosphorylated - PFK-2 is active and FBP-2 is inactive (favors formation of F2,6 Biphosphate)

Methylxanthine derivatives, Theophylline and caffeine

Primary transporter of glucose in the neurons?

Glut-3

Protein kinase A phosphorylates serine or threonine residues and what else?

Proteins that bind to promoter regions of DNA (to cause increased expression of specific genes)
Second Messenger - it intervenes b/w the original messenger (hormone or neurotransmitter) and the ultimate effect on the cell being a part of a cascade of events that translates hormone or neurotransmitter binding into a cellular response

Regulation of metabolism can also occur by a system that uses a hormone or neurotransmitter to elicit a cellular response. What is this system?

The nucleus of the hepatocytes contain a Glucokinase Regulatory Protein (GKRP). What is the mechanism of this protein in Glycolysis?

GKRP - in the presence of Fructose 6P, glucokinase is translocated into the nucleus to bind the GKRP. This inactivates glucokinase. When glucose levels are increase, glucose causes the release of glucokinase from the regulatory protein. Glucokinase then enters the cytosol and phosphorylates glucose to G6P. As glucose levels fall, fructose 6P causes glucokinase to translocate back into the nucleus and bind to the regulatory protein.

What are the 1st five steps in Glycolysis The Energy Investment Phase? Name the steps then name the enzymes What are the 2nd five steps in Glycolysis The Energy Production Phase? Name the steps then name the enzymes What are the activators and inhibitors of PFK-1?

1. Glucose to Glucose 6P (Glucokinase & ATP) 2. G6P to Fructose 6P (isomerized by phosphoglucose Isomerase) 3. F6P to Fructose 1,6 Biphosphate (Phosphofrutokinase 1 & ATP) 4. F1,6BP to Dihydroxyacetone phosphate (DHAP) & Glyceraldehye 3P (cleaved by Aldolase A) 5. DHAP to Glyceraldehyde 3P (by triose phosphate isomerase) Results in net production of 2 molecules of G3P from F1,6BP

6. G3P to 1,3 biphosphoglycerate (Inorganic phosphate + glyceraldehyde 3-phosphate dehydrogenase - oxidation-reduction that requires NAD+ 7. 1, 3 BPG to 3 Phosphoglycerate (phosphoglycerate kinase -generates ATP, 1st substrate level phosphorylation) 8. 3 Phosphoglycerate to 2 Phosphoglycerate (Phosphoglycerate mutase) 9. 2 Phosphoglycerate to Phosphoenolpyruvate (enolase + H2O released) 10. Phosphoenolpyruvate to Pyruvate (Pyruvate Kinase- generates ATP - 2nd substrate level phosphorylation) 2 molecules of Glyceraldehyde 3P where generated from F1,6BP - so net 2ATP at end of Glycolysis & 2 NADH + H+ generated

Activators 1. AMP (signals that cell's energy stores are depleted) 2. Fructose 2,6 Biphosphate - MOST potent activator Inhibitors 1. ATP (Allosteric inhibition - signals that there is an abundance of energy) 2. Citrate (elevated levels inhibit)

What are the most important characteristics of Glucokinase?

1. Found in Liver and Pancreas 2. High Km (low affinity so needs high conc of glucose -n hepatocyte) 3. High Vmax - can metabolize large amount (minimizes hyperglycemia) 4. Regulated by Fructose 6P (indirectly inhibited) 5. Activated by glucose 6. Activated by Insulin (when glucose levels increase - pancreas stimulated to release insulin

What is the common intermediate of the Catabolism of energy rich molecules?

Acetyl - CoA

What is the final common pathway in the oxidation of fuel molecules such as Acetyl CoA? What is the most important route of communication in chemical signaling b/w cells for ENERGY metabolism? What is the primary transporter for fructose?

TCA cycle - large amounts of ATP are made as electrons flow from NADH & FADH2 to oxygen via Oxidative phosphorylation 1. Bloode-borne hormones 2. Neurotransmitters

Glut-5 - in the small intestine and testes

What is the process of G-protein activation thru cAMP after the receptor has been bound by the ligand? What is the process that lead to an increased rate of glycolysis (p.98, lippincott)? What is the sum of all the chemical changes occuring in a cell, a tissue, or the body?
What molecule promotes the transcription of the glucokinase gene, resulting in an increase in liver enzyme protein and a increase in total glucokinase activity?

-subunit of Gprotein is activated by exchange of GDP for GTP, activated -subunit activates adenylate cyclase that catalyzes ATP to cAMP, cAMP binds and activates 2 regulatory units of Protein kinase A releasing the 2 catalytic units. Catalytic units using ATP phosphorylate a protein with final product being Protein phosphorylated + ADP

Increased F2,6BP activates PFK-1, which leads to an increased rate of glycolysis

Metabolism - integrated and purposeful network of chemical rxns [series of rxns that can form pathways (ie glycolysis)] Insulin

What proteins are usually phosphorylated by protein kinase A?

Serine & threonine residues of protein substrates. (these proteins are usually found in the active units of enzymes) Glucokinase - functions as the glucose sensor

What regulates the threshold for insulin secretion?

Which enzyme converts F2,6BP back to Fructose 6P?

Fructose Bisphosphatase-2 (FBP-2) part of a BIFUNCTIONAL Enzyme w/PFK-2.

Which glucose transport system requires energy to transport glucose against concentration gradient? Which glucose transporter are abundant in erythrocytes and brain?

Na+-monosaccharide cotransporter system - occurs in epithelial cells of the intestine, renal tubules and CHOROID plexus. Glut-1

Which glucose transporter is abundant in the adipose tissue and skeletal muscle?

Glut-4 (number of transporters is increased by insulin)

Which glucose transporters are primarily involved in glucose uptake FROM the blood? Which molecule of glycolysis regulates both glycolysis and gluconeogenesis?

Glut-1, Glut-3 and Glut-4

Fructose 2,6 Biphosphate (has reciprocal actions to ensure that both pathways are not active at the same time) Protein Kinase C

Which protein kinase is cAMP independent?

Which transporter can uptake glucose from the blood to the cells or from the cells to the blood?f Which transporter mediates transport of glucose across the endoplasmic reticular membrane?

Glut-2 - found in the liver, kidney and cells of the pancreas

Glut-7