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240

Give an example of competitive inhibition

Succinate is converted to fumarate by succinate dehydrogenase
Malonate is a competitive inhibitor for this reaction

241

How is competitive inhibition reversed?

Increase conc. of substrate to overcome reduced affinity

242

Explain non-competitive inhibition

Inhibitor binds to separate, distinct binding site causing SLIGHT conformation change
Can bind to E or ES and from ESI complex which is inactive

243

Explain the effect on Vmax and Km of non-competitive inhibition

As substrate can still bind Km remains constant
As ESI inactive Vmax reduced

244

Give an example of non-competitive inhibition

Fructose-1,6-diphosphate converted to fructose-6-phosphate by fructose-1,6-bisphosphatase which is inhibited by AMP (binds to separate site) and no fructose-6P produced

245

Explain uncompetitive inhibition

Binding of substrate allows inhibitor to bind forming inactive ESI complex
Inhibitor ONLY binds to ES

246

Explain the effect of uncompetitive inhibition on Vmax and Km

Vmax decreased as enzyme inhibited
Km also reduced as creates better ES binding as only binds to ES (due to equilibrium and Le Chatelier's Principle)

247

What are allosteric modulators?

Substances which can regulate enzyme activity

248

Explain the 2 types of allosteric modulators

Positive: increase enzyme activity, binds to allosteric site causing conformational change to enhance substrate binding
Negative: decrease activity, binds to site causing conformational change to decrease substrate binding

249

What 2 hormones are responsible for regulation of glucose levels?

Insulin: promotes uptake and conversion to glycogen
Glucagon: promotes breakdown of stored glycogen to glucose

250

Name the 2 conditions caused by excess and lack of glucose

Hyperglycaemia: excess glucose, hallmark of diabetes, glucosuria (glucose toxicity)
Hypoglycaemia: lack of glucose, loss of cognitive function, coma, permanent brain damage

251

How is glucose transported into cells in the body?

Intestine: uptake from lumen to epithelial requires active transport
Body: blood to cells (muscle, liver, adipose) passive or facilitated diffusion

252

How is glucose uptake mediated?

GLUT transporters mediate glucose transport into liver, adipose, muscle tissues

253

Describe GLUTS 1-4

GLUT1+3: PM throughout body, low Km 1mM (high affinity), maintain basal blood glucose 3-6mM
GLUT2: liver, pancreatic cells, high Km 15-20mM, (low affinity as liver stores, pancreas produces insulin in high conc)
GLUT4: muscle, adipose, low Km, insulin sensitive (phosphorylated by Metformin (anti-diabetic) increasing insulin sensitivity)

254

How is glucose uptake regulate by insulin and exercise?

Uptake into muscle and adipose increased by insulin which increases no. of GLUT4 transporters in PM (GLUT4 containing vesicles fuse with PM)
Insulin resistance associated with fewer GLUT4 transporters
Exercise recruits GLUT4 transporters to PM in muscle

255

Describe the alternative fates of glucose

Converted to glucose-6P either enter pentose phosphate pathway produce 5C sugar OR glycolysised to pyruvate (gluconeogenesis reproduce glucose-6P)

256

Explain the role of hexokinase in glycolysis

Found in most cells throughout body, phosphorylates glucose to glucose-6P (1st step of glycolysis)
Low Km
Allosteric inhibition by own product (glucose-6P)
Inhibition of HK causes increase in intracellular glucose inhibiting GLUT transporter

257

Explain the role of glucokinase in glycolysis

Phosphorylates glucose in liver and pancreatic B cells
Higher Km - only active when glucose levels are high
In B cells acts as glucose sensors for insulin secretion
Not inhibited by glucose-6P

258

Outline the 10 steps of glycolysis

G-glucose
G-glucose-6P
F-fructose-6P
F-fructose-1,6-bisphosphate
G-glyceraldehyde-3P (+ dihydroxyacetone-P)
G-glyceraldehyde-3P
B-1,3-bisphosphoglycerate
P-3-phosphoglycerate
P-2-phosphoglycerate
P-phosphoenolpyruvate
P-pyruvate

H-hexokinase
P-phosphoglucose isomerase
P-phosphofructokinase
A-aldolase
T-triosephosphate isomerase
G-glyceraldehyde-3P dehydrogenase
P-phosphoglycerate kinase
P-phosphoglycerate mutase
E-enolase
P-pyruvate kinase

259

Explain how phosphofructokinase 1 regulates glycolysis

High ATP conc. allosterically inhibits PFK1 by binding, promotes tense conformation with low affinity for fructose-6P
PFK2 convert fructose-6P to fructose-2,6-bisP (+ ADP) high levels of fructose-2,6-bisP relieves inhibition
High levels of citrate (1st intermediate TCA) inhibits as confers ATP already present
ADP, AMP(extensive ATP hydrolysis) relieve inhibition

260

Define kinases and mutases

Kinase: phosphorylates i.e. transfers PO4 from ATP to substrate
Mutase: transfer PO4 from 1C to another within molecule

261

Describe fermentation

Anaerobic organisms lack respiratory chain, NADH reoxidised as pyruvate converted to more reduced compound

Some organisms convert pyruvate to ethanol oxidising NADH in reaction catalysed by alcohol dehydrogenase

262

Explain how NADH enters the matrix of mitochondria

Oxaloacetate reduced to malate oxidising NADH
Malate enters matrix is oxidised to oxaloacetate reducing NAD+
Oxaloacetate converted to aspartate by glutamate forming a-ketoglutarate
Aspartate leaves matrix, reacts with a-ketoglutarate reforming oxaloacetate and glutamate

263

Describe galactose metabolism

Gladstone phosphorylated to galactose-1P by galactokinase
UDP-glucose reacts with galactose-1P converting to glucose-1P and forming UDP-galactose
Glucose-1P P group moved by phosphoglucomutase to glucose-6P

264

What is the importance of Ca?

Bone: provide structural integrity of skeleton
Biochemical processes: neuromuscular excitability, blood coagulation, hormonal secretion, enzymatic regulation

265

Why must Ca conc. be maintained?

As has role in so many processes extra and intracellular conc. must be maintained

266

Describe the regulation of intracellular [Ca]

Stored in mitochondria and ER
'Pump-leak' transport system: Ca leaks into cytoplasmic compartment, actively pumped into storage sites in organelles to shift away from cytosolic pools

267

What are the 3 fractions of Ca in serum?

Ionised - 50%
Protein-bound - 40%
Complexed to serum constituents - 10%

268

What protein is the majority of protein-bound Ca bound to?

Albumin -90%, binding is pH dependent
Rest is bound to globulins

269

What 2 molecules is Ca complexed to?

Citrate
Phosphate