Exam 3 November 16 Lecture Flashcards
What are the 4 pathways that glucose-6-phosphate can enter?
- gluconeogenesis (liver)
- glycogen synthesis
- glycolysis
- pentose phosphate pathway
What is an overview of glycogen synthesis and breakdown?
- the liver and muscles store excess glucose as glycogen for later use
- glycogen synthesis and breakdown are tightly regulated
- the liver regulates blood glucose levels using glycogen
What is the only organ that can convert glucose-6-phosphate back to glucose?
the liver
What enzymes are regulated in glycogen metabolism?
- glycogen phosphorylase → removes glucose molecules on glycogen
- glycogen synthase → puts glucose molecules on glycogen (put on anomeric carbon so that it can form glycosidic bond with other carbons)
What are the allosteric regulators for glycogen synthase and phosphorylase?
- positive regulator of glycogen synthase: glucose-6-phosphate
- negative regulator of glycogen phosphorylase: ATP, glucose-6-phosphate
- positive regulator of glycogen phosphorylase: AMP
What happens when there is lots of glucose present?
don’t want to release more glucose so it is stored as glycogen
What is glycogenesis and glycogenolysis?
glycogenesis is glycogen synthesis and glycogenolysis is glycogen breakdown to make free glucose
What is the difference in glycogenolysis purpose in liver compared to the muscle?
- liver is the only organ that produces glucose with glucose-6-phosphatase to supply glucose to maintain blood glucose levels and supply glucose to other tissues
- muscle and other peripheral tissues use glycogenolysis to supply energy to the cell through glycolysis
How long does glucose generation from glycogen (liver) maintain glucose levels after a meal?
many hours after a meal
How does liver glycogen last longer?
when some gluconeogenesis contributes to the generation of glucose
Glucose is essential for what?
red blood cells and the brain in which neither of them can use blood lipids for energy → human brain uses 40% of all energy in the body, glucose levels can drop quickly without glucose coming from the intestine (diet) or the liver (glycogen or gluconeogenesis)
What does intense muscle activity generate?
lactate or alanine which can go to the liver (via the Cori or alanine cycle) for gluconeogenesis
What can be used to regenerate glucose-6-phosphate?
pyruvate or lactate in muscle can regenerate glucose-6-phosphate and stored as glycogen → but can’t be released into the blood
During long term fasting, where does gluconeogenesis primarily come from?
amino acids from protein breakdown → typically, muscle protein and blood proteins are lost first
What is the pyruvate dehydrogenase complex?
catalyzes the conversion of pyruvate to acetyl CoA and is located in the mitochondria → reaction is highly exothermic (large negative ΔG and shortens the metabolite by 1 carbon through CO2) and is irreversible in cells → reactions that produce CO2 cannot be reversed in cells due to very low concentration of anhydrous CO2 in cells
What is the PDH reaction catalyzed by?
catalyzed by the PDH complex of many copies of three different functional units → uses 5 different coenzymes in which 4 are derived from vitamins
What are the 5 coenzymes of the PDH complex and what are their functions?
- thiamine pyrophosphate (TPP) aka E1 → decarboxylation and aldehyde group transfer
- lipoic acid aka E2 → carrier of hydrogens or acetyl groups
- NADH → electron carrier
- FADH2 aka E3 → electron carrier
- coenzyme A (CoASH) → acetyl group carrier
What are the substrates of the PDH reaction?
pyruvate, CoASH, NAD+ (which then gets reduced)
What are the products of the PDH reaction?
acetyl CoA (carries acyl group from pyruvate on CoA), CO2, and NADH
What is the function of coenzyme A?
while the β-mercaptoethylamine end can undergo redox to form a disulfide-linked dimer, it primarily acts as an acyl carrier without being oxidized → not a real coenzyme
Animals can make all the parts of coenzyme A except for what?
the pantothenic acid (vitamin B5)
What is acetyl CoA produced from?
glucose, fatty acids, and some amino acids
What is acetyl CoA?
fuel for the TCA cycle and material for fatty acid synthesis and ketogenesis → cannot be used to make glucose
What are ketone bodies?
- water soluble products from lipid oxidation (acetyl-coA) and is produced mostly by the liver during prolonged fasting or on a ketogenic diet (low carbs and high fat)
- concentration can be higher than 3 mM in the blood
- ketogenesis reduces the need for gluconeogenesis → reduces protein wasting
- utilized by many tissues (brain and skeletal muscles) as a fuel
