Metabolic cycle regulation Flashcards
Pyruvate Carboxylase modulators
Positive: acetyl coa (carb flame), glucagon transcription
G-6-phosphatase modulators
Positive: Glucagon transcription
Brain AMPK kinase
Ca2+-calmodulin-dependent kinase B - ca2+ stimulant
Epinephrine
Positive modulator for glycolysis in the muscle to produce ATP.
Pyruvate Kinase modulators
Positive: F-1,6-Bis-P, Insulin via transcription
Negative: ATP, Acetyl CoA, Long Chain FA, Glucagon
Glucagon on metabolic pathways: FA mobilization
Adipose tissue
Positive - PKA, Hormone-sensitive lipase
Phosphfructokinase I modulators
Positive: ADP, AMP, F-2,6-BisP, Insulin via transcription
Negative: ATP, citrate
Insulin on metabolic pathways: Glycolysis, acetyl CoA production
Liver & Muscle
Positive: PFK-1 by PFK2, Pyruvate DH complex, Pyruvate kinase (transcription)
AMPK-P energy producing processes
Heart (glycolysis, glucose uptake, b-oxidation), Skeletal muscle (b-oxidation, glucose uptake), brain (feeding)
AMPK Kinase modulators
Positive: AMP, leptin, adiponectin
F-1,6-Biphosphatase modulators
Negative: F-2,6-bisP
Insulin on metabolic pathways: Triacylglycerol synthesis
Adipose
Positive: Lipoprotein lipase (transcription)
PEP Carboxylase modulators
Positive: Glucagon and Glucagon transcription
Positive Modulators on most energetic steps of Krebs cycle
Ca2+ in the muscle only
Negative Modulators on most energetic steps of Krebs cycle
ATP, NADH+H, FADH2
Glucagon on metabolic pathways: Ketogenesis
Brain
Negative - acetyl-CoA Carboxylase
Adenylate Kinase
Will make AMP from 2 ADPs
Explain why pyruvate carboxylase should be active in fed states
Acetyl CoA is a positive modulator for PC.
Liver fed: excess acetyl Coa with OAA from excess pyruvate make citrate, citrate shuttled to cytosol for FA synthesis.
Succinyl-CoA and odd chain FAS as a negative modulator and why
alpha-ketoglutarate DH and citrate synthase, want to slow down Krebs because we are going faster than ATP synthesis in ETC can occur.
Gluconeogenesis enzymes
G-6-phosphatase, F-1,6-Bisphosphatase, PEP Carboxylase, Pyruvate carboxylase
Explain why hepatocytes express an additional hexokinase isozyme
Hexokinase - outside the liver, lower km, energy needed by extrahepatic cell during low glucose
Glucokinase - liver is dominated by its presence, separate isozyme for glucose phosphorylation, storage needed by hepatic cells at high glucose, higher Km
Glut 1
most important at fasting blood glucose levels
Glucagon on metabolic pathways: Glycogen breakdown/synthesis
Liver
Breakdown - positive glycogen phosphorylase
Synthesis - negative glycogen synthase
AMP
positive modulator for AMPK and AMPK kinases
Major reactions of glycolysis
Hexokinase, Phophofructokinase I, Pyruvate Kinase
AMPK-P Energy consuming procceses
Pancreas (insulin secretion), Liver (FA, cholesterol synthesis), Adipose (FA syntehsis and lipolysis)
Most energetic Steps in Krebs
Pyruvate DH, Citrate Synthase, Isocitrate DH, alpha-ketoglutarate DH
Glucagon on metabolic pathways: Glycolysis/gluconeogenesis
liver
Glycolysis - negative PFK-1
Gluconeogenesis - positive FBPase-2,
negative - PEP carboxykinase (as well as transcription), pyruvate carboxylase, g-6-phosphatase (all transcription
Insulin on metabolic pathways: Glucose uptake
Muscle, Fat – GLUT 4 positive
Liver - Glucokinase (transcription)
Role and modulators of Pyruvate dehydrogenase phosphatase
Activate pyruvate DH via positive modulator insulin and Ca2+
Glucokinase positive modulators
Insulin via transcription
FBPase-2 modulator
Positive: FBPase-2
Glut 4
important after a meal when insulin is released. Only depends on insulin in muscle and adipose. Stored in the ER and recruited to surface by insulin for glucose transport. Once insulin signal is gone it is brought back to the ER
G-6-Phosphatase expression
only expressed in liver and kidneys
Explain why pyruvate carboxylase should be active in the fasted states
Acetyl CoA is a positive modulator.
Muscle Fasted: Excess acetyl CoA from B-oxidation of FA and ketone bodies from the liver.
Liver Fasted: Excess acetyl CoA from B-oxidation of FA. Alanine from muscle makes pyruvate to OAA (using PC)
OAA can’t react with excess CoA because gluconeogenesis uses OAA to make glucose. Excess acetyl CoA used to make Ketone bodies
GLUT 4 modulators
Positive: Insulin via transcription
Insulin on metabolic pathways: Glycogen Synthesis/breakdown
Liver & Muscle – positive glycogen synthase, negative glycogen phosphorylase
Modulators for Pyruvate DH
Positive: AMP, NAD+, CoA
Negative: ATP, NADH, Acetyl-CoA
Hyperglycemic
no AMPK-kinases – Liver kianse B1 - stress stimulant
Role and modulators of pyruvate dehydrogenase kinase
inactivate pyruvate DH via positive modulator ATP
PFK-2 modulators
insulin positive modulator
AMPK modulators
Positive: AMPK
negative: Phosphocreatine
Insulin on metabolic pathways: Fatty acid synthesis
Liver
Positive: Citrate Lyase, acetyl-CoA carboxylase, FAS (transcription)
Glut 2
important immediately after a meal when glucose levels increase and during gluconeogenesis
