Transcript module 3
Whenever pathways are given with compartmental localization, it will usually be important to know the impact of that localization. Glucose (food carbohydrate, blood sugar) phosphofructokinase A little ATP + A little NADH AMP ATP GP shuttle ADP Pyruvate If GP shuttle saturated: Ox. FADH2 NADH Phos. Pyruvate + NADH -> lactic acid. acetyl CoA citrate OA several NADH mitochondrion Fatty acid synthesis NADH ADP + Isocitrate dehydrogenase http://biochem.uthscsa.edu/hardies-bin/survey.pl a) Coordination of glycolysis with fatty acid synthesis is relevant in all tissues. b) Coordination of glycolysis with fatty acid synthesis is relevant in liver, but not in muscle. c) All kinds of tissues tend to produce lactic acid if overworked. d) Liver won’t produce lactic acid. It will take up lactic acid and reconvert it to glucose. Note that the emphasis is on key molecules that connect or interregulate pathways, and on regulatory enzymes. So far, we’ve discussed cell autonomous regulation of glycolysis. Cells also regulate their energy pathways according to overall glucose availability. High blood glucose leads to secretion of the hormone insulin. Low blood glucose leads to secretion of the hormone glucagon. Liver cells have a responsibility to support blood glucose levels by first releasing glucose from their internal glycogen stores, and if necessary synthesizing glucose from amino acids. They will shut down glycolysis and rely on other energy sources for their own needs under these conditions. Liver cells also have a responsibility to convert excess glucose to fatty acids. Under conditions of high blood glucose, they will override the ATP inhibition to allow allow glucose to be converted to citrate, and hence to fatty acids. PFK-2 Regulates Levels of F-2,6bisP Lack of F-2,6bisP essentially shuts down glycolysis in liver, so as not to form a futile cycle with gluconeogenesis (overrides ATP inhibition) Influence of blood sugar on glycolysis in liver. High blood sugar; Insulin Low blood sugar; glucagon Glucose (food carbohydrate, blood sugar) phosphofructokinase A little ATP + A little NADH AMP ATP GP shuttle ADP Pyruvate If GP shuttle saturated: Ox. FADH2 NADH Phos. Pyruvate + NADH -> lactic acid. acetyl CoA citrate OA several NADH mitochondrion Fatty acid synthesis NADH ADP + Isocitrate dehydrogenase In gluconeogenic tissues (liver, kidney, intestines), glycolysis has to be reciprocally regulated with gluconeogenesis to avoid futile cycling. Most of the enzymes in gluconeogenesis and glycolysis are the same. Key irreversible steps are bypassed by a different enzyme in gluconeogenesis. gluconeogenesis glycolysis F-6-P fructose bisphosphatase ATP phosphofructokinase F-1,6-P ADP F-2,6-P, AMP,insulin – F-2,6-P, AMP, insulin + ATP, citrate, glucagon + ATP, citrate, glucagon - The role of different resources in consolidating you knowledge: Wikipedia is a great resource to rapidly update or remind yourself of some basic information. However, Wikipedia, class notes from other universities on the web, and the primary literature can lead you into substantial complications that your instructor chose to ignore. For example, there are five different versions of PFK2 with different sensitivities to insulin and glucagon regulation, and expressed in differrent tissues. The instructor in this course chose to only talk about reciprocal regulation of glycolysis and gluconeogenesis in the liver. Lecture slides reveal what the instructor chose to discuss and indicate a level of detail. He probably went into greater detail than he expected you to be able to reproduce on the exam. Looking at past exams will help clarify his expectations of you. If you missed a point in lecture, you will probably not be able to figure out what it was by looking at the lecture slides. The lecture slides generally have just pictures and not sentences. The course manual will usually cover the same material, but with sentences. The course manual is not up to date with the lectures in all cases. Summary: For each pathway: What is if for and how is it regulated is of the highest priority. Names of regulatory enzymes and molecules that regulate or coordinate the pathway with other pathways are of the highest priority to know by name. Subcellular localization and movement of molecules between compartments to support the pathway is usually of relevance to know. If the pathway is described as localized to a tissue, that would be important to know. It should make sense with respect to your understanding of the role of that tissue in support of global metabolism. If hormonal regulation is specified, that is always important to know. It should make sense with respect to what physiological state the hormone signifies. How is glycolysis regulated? a) b) c) d) e) Which one of the following statements about glycolysis if FALSE? a) b) c) d) e)