8. Basic metabolism

Question 1

define metabolism

Answer 1

sum of all chemical changes occurring in a cell, tissue or body

Question 2

define metabolic pathway

Answer 2

a series of enzymatic reactions producing specific products - branches and interconnected

Question 3

degradative pathway

Answer 3

catabolic metabolised in central oxidative pathway - convergent variety of molecules common end products energy releasing

exergonic (delta G<0)

energy contained in ADP

Question 4

biosynthetic pathway

Answer 4

anabolic

few metabolites at starting point (divergent- many end products)

endogenic (delta G> 0) requires energy ATP

Question 5

define metabolic flux

what is it determined by

Answer 5

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

Question 6

How do cells control lux through these rate-determining steps?

Answer 6

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

Question 7

how much energy do carb, proteins and fat yield and what is the recommended intake

Answer 7

4 kcal, 4 and 9

c: 55% p: 15% f: 30%

Question 8

Digestion of carbohydrates

Answer 8

1. (starts with polysaccharides) mouth: amylase to oligossacharides
2. further digestion into small intestine by pancreatic enzymes (amylase)
3. final digestion of disaccharides to monosaccharides by enzymes on mucosal cells

glucose taken into cells along with Na+ by active transport

Question 9

Glucose,

why is it important?

what forms does it exist in?

how is it stored?

Answer 9

most abundant carb in human body

D or L enantiomers

found in plasma and stored as glycogen

Question 10

what does glucose form in solution

Answer 10

6 membered ring structure- pyranose

anomeric carbon- exists in alpha and beta

Question 11

concentration of glucose in fasting and following high carb meal

Answer 11

fasting: 4

after meal: 8 mmol

Question 12

how is blood glucose concentration controlled

Answer 12

hormones

Question 13

what requires glucose

Answer 13

brain and erythryocytes (no mitochondria)

Question 14

How does glucose enter cells

Answer 14

1. Na+ independent faciliated diffusion transport
2. ATP- dependent Na+ monosaccharide transport

Question 15

Na+ - independent facilitated diffusion transport

Answer 15

• glucose moves via concentration gradient
• GLUT 1 to 14 diff isoforms (tissue-specific expression)
• GLUT 4 is common in muscle & adipose (insulin increased)

Question 16

ATP-dependent Na+-monosaccharide transport system

Answer 16

• a “co-transport” system
• transports glucose against a gradient (coupled to Na+ gradient)
• found in intestinal epithelial cells

Question 17

What happens when you irreversibly phosphorylate glucose?

Answer 17

traps it into cytosol and commits it as phosphorylated sugars cant cross cell membrane easily

Question 18

Glycolytic reactions: 1

what catalyses this reaction?

how does this differ in other cells?

Answer 18

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

Question 19

Glycolysis: 2

Answer 19

Isomerisation

glucose 6-phosphate to fructose 6-phosphate

• catalysed by phosphoglucose isomerise
• reversible & not rate limiting

Question 20

Glycolysis: 3

Answer 20

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

Question 21

what is PFK-1 controlled by

Answer 21

[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

Question 22

Glycolysis 4,5

Answer 22

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

Question 23

Glycolysis 6 and 7

Answer 23

6. redox

Glyceraldegyde 3-P oxidised (NAD+-> NADH) and gains phosphate to become 1,3- Biphosphoglycerate

catalysed by glyceraldehyde-3-phosphate dehydrogenase

7. 3- phosphoglycerate

catalysed by phosphoglycerate kinase

2ADP-> 2ATP

both reversible

Question 24

Glycolysis 8-10

Answer 24

8. 3-phosphoglycerate to 2-phosphoglycerate

phosphate group shift

catalysed by phosphoglycerate mutase

reversible

9. Phosphoeynolypyruvate

dehydration reaction

catalysed by enolase

reversible

10. pyruvate

substrate level phosphorylation

catalysed by pyruvate kinase

2ADP-> 2ATP

irreversible

Question 25

Anaerobic glycolysis

Answer 25

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

Question 26

Answer 26

Question 27

What leads to haemolytic anaemia

Answer 27

genetic defects of glycolytic enzymes lead

majority: defect in pyruvate kinase

Question 28

what happens if RBC lack glucose

Answer 28

cannot fuel ion pumps to maintain shape

• shape changes and phagocytosis