carbs Flashcards
Glucose transporters
- insulin sensitive – Glut 4 – increases glucose transport in cell following insulin exposure (sk muscle/adipose)
- insulin independent- Glut 2 - in liver–
where does glycolysis occur
cytoplasm
3 types of chemical reactions in glycolysis
- degrade glucose –> pyruvate
- phosphorylate ADP –> ATP
- generation of NADH
substrate level phosphorylation
phosphorylate ADP-> ATP during glycolysis
oxidative phosphorylation
in mitochondria
First reaciton in glycolysis
glucose –> G6P
- hexokinase or glucokinase mediated
- irreversible
what does glucose phosphorylation accomplish
- give intermediate net charge to trap it in cell
- conserves energy
- binding of G6P phosphate to active site of next enzyme lowers activation energy
Hexokinase I
- not selective
- in all cells
- low Km for sugars
- Inhibited by G6P
- more active at lower glucose concentrations(i.e. during fasting)
Glucokinase
- selective for glucose
- liver, pancreatic Beta-cells
- High Km for glucose
- inhibited by F-6-P
- more active at higher glucose concentrations
PFK1
catalyzes reaction of F6P -> F 1, 6 bisphosphate
- 2nd ATP investment
- rate-limiting and committed step of glycolysis
- irreversible
- allosteric enzyme
what inhibits PFK 1
ATP/citrate
what stimulates PFK 1
AMP
PFK2
can convert F6P to F 2,6, BP
F2,6BP most potent activator of PFK1
5 parts of cab metabolism
Glycolysis, TCA cycle, Gluconeogenesis, Glycogen synthesis/breakdown, Pentose Phosphate Pathway
Km
concentration at which reaction is half maximal
- Low Km = substrates have strong affinity for enzyme and reaction will go at low substrate concentrations
-
Vmax
maximal rate an enzyme-catalyzed reaction
- High Vmax = produce a lot of product in small period of time
3 types of key steps
1- molecule changes location in cell (moves across membrane)
2 - body invests energy (often P from ATP)
3- rate-limiting step
Key steps in glycolysis
- Glucose enters cell
- Glucose –> G6P
- F6P –> F1,6,BP
- PEP –> pyruvate
significance of G6P
phosphorylating glucose traps it within cell due to charge
Rate-limiting step of glycolysis
F6P–> F1,6BP via phosphofructokinase (PFK)
Fate of pyruvate
- with O2 –> TCA cycle
- No O2 – convert to lactate and exported from cell; regenerates NAD from NADH to allow continuation of glycolysis
- pyruvate from lactate or amino acid metabolism can also enter TCA as oxaloacetate during gluconeogenesis
where does glycolysis happen
cytosol of cell
Where is the electron transport chain
inner mitochondrial membrane
Key regulated steps in gluconeogenesis
1) Pyruvate –> PEP through oxaloacetate and malate; pyruvate carboxylase and PEP carboxykinase
2) F1,6BP –> F6F via Fructose1,6bisphosphatase
3) G6P –> Glucose: allows it to leave cell and only happens in liver/kidney (NOT muscle/adipose)
Sources of carbon for gluconeogenesis
(these substrates transported to liver)
- lactate from glycolysis in muscle or RBC
- amino acids from protein breakdown in muscle
- glycerol from triglyceride breakdown in adipose tissue
Glycogen
- when excess glucose
- G6P -> G1P -> UDP-glucose : key step for synthesis/breakdown
- 2nd key step adds UDP-glucose to glycogen molecules with glycogen synthase (removes with Glycogen phosphorylase)
Glycogen phosphorylase
removes glucose from glycogen when needing glucose
how is glucose added to glycogen
- add individual glucose in 1,4 orientation
- for breakdown, glycogen broken from terminal ends until branch point – enzyme takes apart branch point
Functions of pentose phosphate pathway
- Generate NADPH for fatty acid biosynthesis, cholesterol biosynthesis, defense against oxidative stress and white cell function
- generate 5 carbon sugars for nucleotide synthesis
key regulated step in pentose phosphate pathway
Glucose-6-Phosphate dehydrogenase (G6P –> 6 phosphogluconolactone)
Regulation through pathway depends on
- amount of substrate
- levels/amount of key enzymes
- allosteric regulation– can change Km or Vmax
- Covalent modification (phosphorylation)–common with hormones (insulin/glucagon)–can also change Km or Vmax
How can the body change Km or V max of a reaction
allosteric regulation or covalent modification of key enzyme
Counter-regulatory hormones
glucagon, catecholamines, growth hormone, cortisol
What happens in fed state
Insulin high, counter regulatory hormones low,
- glycolysis/glycogen synthesis active and glucose assimilated by peripheral tissues
- gluconeogenesis/glycogen breakdown reduced
fasting state
- Insulin low, counter-regulatory hormones high
- Gluconeogenesis/glycogen breakdown increased
