8. Basic metabolism Flashcards
define metabolism
sum of all chemical changes occurring in a cell, tissue or body
define metabolic pathway
a series of enzymatic reactions producing specific products - branches and interconnected
degradative pathway
catabolic metabolised in central oxidative pathway - convergent variety of molecules common end products energy releasing
exergonic (delta G<0)
energy contained in ADP
biosynthetic pathway
anabolic
few metabolites at starting point (divergent- many end products)
endogenic (delta G> 0) requires energy ATP
define metabolic flux
what is it determined by
net rate of movement
steady state of flux maintained delta G=0
determined by rate determining step (slowest, largest negative delta G)
- relatively insensitivity to [substrate] permits establishment of steady state
How do cells control lux through these rate-determining steps?
1. allosteric control
2. covalent modifiation: shorter control than genetic but longer time to respond
3. substrate cycles- vary rates of two opposing non equilibrium reactions
4. genetic control: changes within hours and days, long term control
how much energy do carb, proteins and fat yield and what is the recommended intake
4 kcal, 4 and 9
c: 55% p: 15% f: 30%
Digestion of carbohydrates
- (starts with polysaccharides) mouth: amylase to oligossacharides
- further digestion into small intestine by pancreatic enzymes (amylase)
- final digestion of disaccharides to monosaccharides by enzymes on mucosal cells
glucose taken into cells along with Na+ by active transport
Glucose,
why is it important?
what forms does it exist in?
how is it stored?
most abundant carb in human body
D or L enantiomers
found in plasma and stored as glycogen
what does glucose form in solution
6 membered ring structure- pyranose
anomeric carbon- exists in alpha and beta
concentration of glucose in fasting and following high carb meal
fasting: 4
after meal: 8 mmol
how is blood glucose concentration controlled
hormones
what requires glucose
brain and erythryocytes (no mitochondria)
How does glucose enter cells
- Na+ independent faciliated diffusion transport
- ATP- dependent Na+ monosaccharide transport
Na+ - independent facilitated diffusion transport
- glucose moves via concentration gradient
- GLUT 1 to 14 diff isoforms (tissue-specific expression)
- GLUT 4 is common in muscle & adipose (insulin increased)
ATP-dependent Na+-monosaccharide transport system
- a “co-transport” system
- transports glucose against a gradient (coupled to Na+ gradient)
- found in intestinal epithelial cells
What happens when you irreversibly phosphorylate glucose?
traps it into cytosol and commits it as phosphorylated sugars cant cross cell membrane easily
Glycolytic reactions: 1
what catalyses this reaction?
how does this differ in other cells?
Glucose phosphorylation -> glucose-6-phosphate
catatlysed by hexokinase I-III in most tissues (uses ATP)
irreversible
inhibited by glucose-6-phosphate
- low Km (high affinity for glucose)
- permits efficient phosphorylation in low [glucose]
- low Vmax means no overabundance of glucose 6-phosphate
glucokinase (hexokinase IV) in liver parenchymal cells
- Higher Km so only active following consumption of carb-rich meal
- High Vmax allowing glucose delivered to liver to be maximally absorbed
Glycolysis: 2
Isomerisation
glucose 6-phosphate to fructose 6-phosphate
- catalysed by phosphoglucose isomerise
- reversible & not rate limiting
Glycolysis: 3
Fructose 6-phosphate Phosphorylation
to fructose-1,6- biphosphate
-An irreversible reaction, rate-limiting
catalysed by phosphofructokinase-1
-The most important control point
ATP-> ADP
what is PFK-1 controlled by
[ATP] (high- inhibition) / [AMP]
[fructose 6-phosphate]
fructose-2,6- bis phosphate
- PFK-2 produces F-2,6BP and phosphatase activity that dephosphorylates F 2,6 BP to F-6-BP
inhibited by high citrate levels-> favours glycogen synth
Glycolysis 4,5
F-1,6-BP cleavage
to DHAP (dihydroxyacetone-P) used in triacylglycerol synthesis
and 2x Glyceraldehyde 3-P (3C)
catalysed by adolase
reversible and unregulated
Triose Phosphate Isomerise allows interconversion
Glycolysis 6 and 7
- redox
Glyceraldegyde 3-P oxidised (NAD+-> NADH) and gains phosphate to become 1,3- Biphosphoglycerate
catalysed by glyceraldehyde-3-phosphate dehydrogenase
- 3- phosphoglycerate
catalysed by phosphoglycerate kinase
2ADP-> 2ATP
both reversible
Glycolysis 8-10
- 3-phosphoglycerate to 2-phosphoglycerate
phosphate group shift
catalysed by phosphoglycerate mutase
reversible
- Phosphoeynolypyruvate
dehydration reaction
catalysed by enolase
reversible
- pyruvate
substrate level phosphorylation
catalysed by pyruvate kinase
2ADP-> 2ATP
irreversible
Anaerobic glycolysis
In anaerobic conditions (e.g. strenuous exercise) the respiratory chain cannot oxidise NADH to regenerate NAD+ (requires O2)
Pyruvate reduced to lactate by lactate dehydrogenase (LDH) to regenerate NAD+
Different LDH isozymes in different tissues
What leads to haemolytic anaemia
genetic defects of glycolytic enzymes lead
majority: defect in pyruvate kinase
what happens if RBC lack glucose
cannot fuel ion pumps to maintain shape
- shape changes and phagocytosis
