BMS2021 Lecture Notes - Lecture 2: Cytosol, Enzyme, Phosphofructokinase 2
30 May 2018
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Week 1. Metabolic pathways in the liver
METABOLIC PATHWAYS IN LIVER
• Portal vein carries nutrients to liver
o Amino acids can be stored and initially used for anabolic reactions for the synthesis of small
liver proteins (eg. Plasma) -> then oxidised to pyruvate/acetyl CoA
• Provides glucose and ketones for other organs
• Processes amino acids into urea
• Stores nutrients (eg. Fe ion, fat-soluble vitamins)
• Detoxifies and solubilise organic compounds via cytochrome P450 system
• Liver cell unique features:
GLUT2 transporter
o Allows passive diffusion of glucose
o During glycogen beak down or after a
meal
Glucokinase (hexokinase IV)
o Phosphorylation of glucose
(glucose -> G-6-P)
o Has higher Km levels than other
hexokinases; G-6-P is’t ade whe
low glucose
o Not inhibited by G-6-P
• Fructose, galactose and mannose are also converted to G-6-P
find more resources at oneclass.com
find more resources at oneclass.com
Fates for G-6-P in liver:
o Dephosphorylated to yield free glucose to send to other
tissues
o Made into liver glycogen
o Enter glycolysis, to form acetyl CoA then ATP for use by
the hepatocytes
o Enter glycolysis, form acetyl CoA to be made into fatty
acids and later TAGs
o Enter pentose phosphate pathway to yield NADPH and
ribose-5-phosphate
Fates for Amino acids in liver:
o Make into proteins for liver and other tissues
o Make into hormones, nucleotides
o 3) Make into CAC intermediates or pyruvate:
a. for gluconeogenesis
b. convert pyruvate to acetyl-CoA for:
i. liver cell energy
ii. conversion to lipids
Fates for Fatty acids (FA) in
the liver:
o Use FA to synthesize liver lipids
o Oxidize FA to acetyl-CoA and NADH
a. -> CAC and oxphos -> ATP (FA are primary fuel for
liver)
b. Excess acetyl-CoA ketone bodies for brain, heart, etc.
in carbohydrate restriction, fasting
c. Some acetyl-CoA cholesterol
o Convert FA to phospholipids
o Convert FA to TAGs for storage
o Carry FA to heart and muscle for oxidation
find more resources at oneclass.com
find more resources at oneclass.com
• Lipid bilayer overview:
• Cellular transport of glucose across membranes
o Facilitated transport via GLUT1-5
o ~4.5mM in blood plasma ( much lower in cytoplasm
o Glucose uptake by rai ad RBS’s are isuli-independent (with transporters)
o Glucose uptake by muscle and adipose tissues are insulin-dependent (with transporters)
• Glucose transporters
GLUT1
o Present in most cells
o Basal glucose uptake
GLUT2
o In liver, pancreatic islets and intestine
o Conformation change when binds to glucose
o Removal of excess glucose from blood
o Pancreas: regulation of insulin release
-glucose uptake signals blood glucose is high -> secrete insulin
o Liver: maximal glucose uptake when blood glucose levels are high
o Has high Km
GLUT4
o In muscle, fat and heart
o Activity increased by insulin
o Transporters are stored within cell in a membrane vesicle
o Expression stimulated by insulin
myocytes -> synthesise glycogen
adipocytes -> synthesise triacylglycerols
o Type I diabetes: no insulin release -> no mobilisation of GLUT4
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Glut2 transporter: allows passive diffusion of glucose, during glycogen beak down or after a meal. Glucokinase (hexokinase iv: phosphorylation of glucose (glucose -> g-6-p, has higher km levels than other hexokinases; g-6-p is(cid:374)"t (cid:373)ade whe(cid:374) low glucose, not inhibited by g-6-p, fructose, galactose and mannose are also converted to g-6-p. Glut2: present in most cells, basal glucose uptake. In liver, pancreatic islets and intestine: conformation change when binds to glucose, removal of excess glucose from blood, pancreas: regulation of insulin release. Glucose uptake signals blood glucose is high -> secrete insulin: liver: maximal glucose uptake when blood glucose levels are high, has high km. Strategies for metabolic control: enzyme regulation, different proteins in the same tissue have very different half-lives. Destroyed by proteases (a. a sequences are susceptible to attack by proteolytic enzymes or ubiquitination which makes them targets for specific proteases. Repression usually by end product (eg. pfk-1 is inhibited by atp)
