basic metabolism 2

Question 1

degradative pathways [catabolic]

Answer 1

• often converge on common intermediates

- these are further metabolised in common oxidative pathways e.g. TCA cycle

Question 2

biosynthetic pathway

Answer 2

• carry out the reverse reactions

- relatively limited set of building blocks

Question 3

metabolic flux

Answer 3

• control the flux between different metabolic pathways to maintain concentrations of key components
• they are in a steady-state, requiring continual energy input
• flux is determined by the rate-limiting [slowest] step, often irreversible
• these are zero order [rate independent of [substrate]] enabling steady-state to form
• control is both short and long term

Question 4

how is flux controlled?

Answer 4

• substrate cycles; coordinate control of opposing non-equilibrium reactions
• covalent modification [medium-term]
• genetic control: gene transcription and protein synthesis/degradation rates affect enzyme amounts and activities.
• longer term

control often takes place via multiple strategies and at multiple non-equilibrium steps

Question 5

digestion of carbs

Answer 5

starts in the mouth, salivary amylase breaks down polysaccharides into oligosaccharides

• pancreatic enzymes, break these down further in small intestine.
• final digestion of disaccharides to monosaccharides occurs in mucosal cells
• glucose is co-transported into cells along with Na+ [an active process]

Question 6

glucose

Answer 6

• exists in D and L enantiomers
• found in plasma, cells
• comes from diet/ body stores
• stored as the insoluble polymer glycogen [animal starch]
• is in equilibrium with glucopyranose [6-membrerd ring] in solution
• as C1 then asymmetric, alpha and beta anomers
• 5-membered rings are furanoses

Question 7

glucose transport

Answer 7

glucose cannot cross the lipid bilayer.
2 transporter systems:
(A) Na+ -independent transport
(B) ATP-dependent Na+-co-transporter

Question 8

Na+ independent glucose transport

Answer 8

glucose moves down the concentration gradient.
14 subtypes (GLUT-14) with tissue-specific expression

Question 9

ATP-dependent Na+-co-transporter glucose transport

Answer 9

ATP-dependent transporter; works against concentration gradient.
co-transports monosaccharides and sodium [utilizing Na+ gradient in cells]. found in intestinal epithelial cells

Question 10

glycolytic reactions- step 1

Answer 10

• glucose phosphorylation is catalysed by hexokinase [1-111] in most tissues
• one of 3 regulatory checkpoints in glycolysis- product inhibition
• in human enzyme two homologous domains, one catalytic, one regulatory
• low Km [high affinity], low Vmax permits phosphorylation in low [glucose] without product over-abundance

Question 11

phosphofructokinase regulation

Answer 11

• the first step that leads irreversibly to glucose metabolism
• therefore very tightly controlled, to ensure the enzyme is only active when there is energy demand
• controlled by [ATP], [AMP], and [fructose 6-phosphate] (substrate)
• [ATP]high-> inhibition
• [AMP]high-> activation
• also inhibited by citrate [intermediate of TCA cycle]
• inhibition favours glycogen syntheis

Question 12

mature red blood cells

Answer 12

• lack mitochondria and nucleus
• dependent on glycolysis for ATP generation [required to maintain shape through ion-pumps]
• insufficient ATP leads to cell shape changes and phagocytosis

Question 13

haemolytic anaemia:

Answer 13

• genetic defects in glycolytic enzymes affect RBCs
• most involve mutations to pyruvate kinase
• require regular transfusions

Question 14

adenosine triphosphate

Answer 14

• ATP hydrolysis is exergonic
• phosphorylation of ADP is endergonic
• gamma-phosphate bond of ATP [P~O] is a high energy bond