BCH210 Lecture 17 & 18 (carbohydrate metabolism)

lecture 17,

during the anabolic state, how is insulin signalling affected for carbohydrate metabolism

insulin signalling increases glucose utilization

• increasing glucose transport into cells

• increasing the expression and activity of enzymes that use glucose as a substrate

during the catabolic state, how is epinephrine and glucagon signalling affected for carbohydrate metabolism

epinephrine and glucagon signal the release of glucose stroes and decrease glucose utilization

what are the four pathways involved in carbohydrate metabolism

1. glycogen synthesis

2. glycogenolysis

3. glycolysis

4. anaerobic metabolism

what is glycogen synthesis pathway do

storage of excess glucose as glycogen in liver/muscle cells

what does glycogenolysis pathway do

breaks down glycogen to release free glucose

what does glycolysis do

essential for ATP production from simple monosaccharides (Glucose, fructose and galactose)

what does anaerobic metabolism do

converts pyruvate to lactate in anerobic conditions

what two things regulate glycolysis

glucose and atp availability

GLYCOLYSIS: how many steps are in involved, where does it occur, what are the substrates and products, explain the stages 1 (step 1-5) and 2 (step 6-10)

• 10 step pathway

• takes place in the cytoplasm

stage 1 → (energy input) preparation; 2 atp are used to prepare the glucose molecule for breakdown

• generates 2 GAPs (3 carbons)

stage 2 → energy output

• produces 2 pyruvate (3 carbons), 2 NADHs and 4 ATPs

substrates: glucose

products: 2 ATP, 2 pyruvate, 2NADH

what happens to the pyruvate produced in glycolysis

anaerobic conditions → becomes lactate

aerobic conditions → mitochondria, acetyl coA or oxaloacentate makes CO2 and NADH

why is glycolysis energetically favourable /exergonic , which steps cause this

steps 1,3,10 are irreversible due to lots of E released (big - number delta G)

how is glycolysis regulated

at step 1: hexokinase can be inhibited by build up of product ( glucose 6 phosphate)

at step 3: phosphofructokinase 1 (PFK-1) is inhibited by the amount of ATP or citrate present and activated by the amount of AMP, ADP or fructose 2,6 biphosphate 

at step 10: pyruvate kinase is inhibited by phosphorylation and other allosteric regulators 

also- the availability of glucose regulates glycolysis 

what does hexokinase do

phosphorylates many hexos and traps glucose in the cell because GLUTs cant bind to glucose g phosphate 

what does glucose-6-P do for the cell its trapped in

can generate energy, be stored (if in liver or muscle cells), make new molecules from it

how does hexokinase binding occur, how is binding regulated

1. ATP and Mg bind to a domain away from glucose binding in the active sites

2. substrates bind in the active site via charged and polar residues-→ causes a conformational change where the enzyme closes around the substrate

3. C6 hydroxyl attacks the gama phosphate producing glucose 6-phosphate

regulated

• G6P binds to active site → inhibited

• G6P binds to allosteric site → inhibited

• insulin increases gene expression → activated 

what does phosphofructokinase (PFK-1) do, how is it regulated

transferes a phosphate group from ATP to the C1 hydrozyl of F-6P

regulated allosterically

• inhibited allosterically by atp and citrate

• activated allosterically - by amp or adp and fructose 2,6 bisphosphate binding to the allosteric site stimulates PFK-1

NOTE: PFK-1 has 2 ATP binding sites; the active site and an allosteric site

other regulation mechanisms

• insulin activates

• glucagon inactivates

how is pyruvate kinase regulated

It is activated when glycolysis should continue (F1,6BP, insulin) and inhibited when energy is high (ATP, alanine) or when the liver must spare glucose (glucagon → phosphorylation).