Carbohydrates & Glycolysis Flashcards
What are the 4 stages of carb catabolism?
1: breakdown to building block molecules,
2: breakdown to metabolic intermediates – release of reducing power,
3: krebs cycle – release of reducing power,
4: oxidative phosphorylation ATP prod
How does stage 1 of carb catabolism occur?
Salivary/pancreas amylase, enzymes on the brush border of the small intestine: lactase, sucrase, isomaltase
How does lactose intolerance develop?
PRIMARY: absence of lactase persistence allele – only occurs in adults.
SECONDARY: injury to SI = gastroenteritis, coeliac, crohns, ulcerative colitis.
CONGENITAL: extremely rare, autosomal recessive, cannot digest breast milk
How are monosaccharides absorbed?
Active transport by SGLT1 to intestinal epithelial cells, then GLUT2 to blood, then GLUT1-5 from blood into cells
Where are GLUT2 found?
Kidney, liver, pancreatic beta cells, SI
Where are GLUT4 found?
Adipose tissue, striated muscle (insulin-regulated)
Which cells have an absolute glucose requirement?
RBCs (do not have energy stored), neutrophils, kidney medulla, lens of eye (can’t have capillaries blocking site)
Why does the brain not have an absolute glucose requirement?
Prefers glucose but can use ketone bodies for some fuel requirements in times of starvation but need time to adapt
What does stage 2 of carb catabolism produce and how?
Pyruvate by glycolysis
Glycolysis can be broken down into what 2 phases?
Phase 1 = investment phase, 2 ATP in, making glucose –ve increasing reactivity to permit subsequent steps, large –ΔG so irreversible, committing step.
Phase 2 = payback phase, 4 ATP out, substrate level phosphorylation, large –ΔG so irreversible.
How many enzymes are used in glycolysis?
10
In what stage of glycolysis is NADH produced?
Phase 2 = payback phase
What is the function of hexokinase?
phosphorylates hexoses (6C sugars), forming G-6-P
What is the function of phosphofructokinase-1?
regulatory allosteric enzyme made of 4 subunits,
phase 1 = investment phase,
involved in committing step,
conversion of fructose 6-phosphate and ATP to fructose 1,6-bisphosphate and ADP,
inhib by high ATP and glucagon,
stim by high AMP and insulin
Outline the function of pyruvate kinase
catalyses the final step of glycolysis:
stim by high insulin,
transfer of a phosphate group from phosphoenolpyruvate (PEP) to adenosine diphosphate (ADP) = pyruvate and one molecule of ATP
During glycolysis how many irreversible steps are there?
3
In what pathology is the rate of glycolysis greater?
Cancer – this can be measured by uptake of radioactive modified hexokinase substrate
Which reaction in glycolysis is NAD+ required?
Reaction 6
How is NAD+ regenerated?
Lactate dehydrogenase
What does NAD+ and NADH do?
Nicotinamide adenine dinucleotide exists in two forms, an oxidized and reduced form abbreviated as NAD+ and NADH respectively.
In metabolism, NAD+ is involved in redox reactions, carrying electrons from one reaction to another
What reaction does lactate dehydrogenase catalyse
NADH + H+ + pyruvate NAD+ + lactate
What is hyperlactaemia?
Lactate 2-5mM, below renal threshold, no change in blood pH as buffering capacity
What is lactate acidosis?
> 5mM, above renal threshold, blood pH lowered
Deficiencies in which 3 enzymes cause galactosaemia?
Galactokinase,
UDP-galactose epimerase,
uridyl transferase
When fructokinase is absence what occurs?
Essential fructosuria: fructose present in the urine but no clinical signs
Explain fructose intolerance
Aldolase is missing, fructose accumulates in the liver = damage
Treat = remove fructose from diet
The pentose phosphate pathway is an important source of what?
NADPH
What does the pentose phosphate pathway result in?
C5-sugar ribose required for the synthesis of: nucleotides, DNA, RNA
The rate limiting enzyme of the pentose phosphate pathway is?
Glucose 6-phosphate dehydrogenase
What part of carb catabolism can operate anaerobically?
Glycolysis, with the addition of the enzyme LDH
What are the main features of glycolysis?
6C sugar to 2x 3C sugar = pyruvate,
ATP needed to be invested to activate glycolysis,
lower down the pathway is an oxidation step in which NAD taking reducing equivalents from intermediates,
lower down there is steps of substrate level phosphorylation = phosphate removed transferring to ADP making ATP,
galactose and fructose entering the pathway – being metabolised,
if energy is high glycolysis is switched down = substrate is diverted out – prod NADPH,
if no O2 to re-oxidase NADH can use LDH
When ATP is high in skeletal muscle, energy may be temp stored in which substrate?
Phosphocreatine = stores phosphate bond energy
What is the chem formula for glucose?
C6 H12 O6
Which glucose transporter is regulated by insulin?
GLUT4
What is the net prod of ATP from 1 molecule of glucose in glycolysis?
2
