Glycolysis Flashcards
Glycolysis
1 ATP phosphorylate glucose in phase 1 (investment) to glucose-6-phosphate
G-6-P phosphorylated by 1 ATP again
Form 2 C3 molecules (inconvertible)
On each molecule NAD+ reduced to NADH, 2 ADP is phosphorylated to ATP in SL phosphorylation
Pyruvate formed (C3)
1 ATP phosphorylate glucose in phase 1 (investment) to glucose-6-phosphate
- 1st phosphorylation catalysed by hexokinase
- G-6-P is -ve charged
- prevents passage back across plasma membrane
- increases reactivity to permit subsequent steps
- allows SL phosphorylation to later occur
G-6-P phosphorylated by 1 ATP again
- Both phosphorylation has large -ve ∆G value
- irreversible
- reaction 3: committing step - commits glucose to metabolism
On each molecule NAD+ reduced to NADH, 2 ADP is phosphorylated to ATP in SL phosphorylation
- 2nd phosphorylation as large -ve ∆G
- irreversible
- occurs with pyruvate kinase
Describe how key metabolites may be derived from glycolysis
Glycerol phosphate important to triacylglycerol + phospholipid synthesis
- produced from dihydroxyacetone phosphate (intermediate of glycolysis) in adipose
Liver less dependent
- can phosphorylate glycerol directly using glycerol kinase + ATP
RBC use 1,3-bisphosphoglycerate to produce 2,3-bisphosphoglycerate
- important regulator of o2 affinity of Hb
Regulation of Phosphofructokinase
- Allosteric regulation (muscle)
- inhibit by high ATP (ratio), high citrate
- stimulated by high AMP, F2,6,BP
- Hormonal regulation (liver)
- inhibited by glucagon
- stimulated by insulin
• Explain why lactic acid (lactate) production is important in anaerobic glycolysis.
NADH is converted back to NAD+ in lactate dehydrogenase reaction (LDH)
- enables anaerobic resp to continue
• Explain how the blood concentration of lactate is controlled.
heart, liver & kidney can utilise lactate
- LDH works in reverse direction to produce pyruvate
- NAD+ reduced to NADH + H+
deficiency of galactokinase
- accumulation of galactose
- cataracts, no jaundice
deficiency of uridyl transferase
accumulation of galactose & galactose-1-phosphate (toxic to kidney, brain, esp liver)
- cataracts, liver failure (affects other organs), jaundice
deficiency of UDP-galactose epimerase
- prevents inter conversion of UDP-galactose and UDP-glucose
- prevents glycogenesis: formation of glycogen
- symptoms tend to be milder as glycogenesis can occur in other parts of the body
- galactose not present in urine
- symptoms tend to be milder as glycogenesis can occur in other parts of the body
Cataracts
galactose reduced by NADPH to NADP+ and galactitol, by aldose reductase
- depletes NADPH: GSSG not reduced back to GSH
- less protection against damage from oxidative stress - changes protein shape
- less transparent lens: cataracts
what occurs in pentose phosphate pathway
- G-6-P is oxidised by NADP+ forming NADPH using glucose-6-phosphate dehydrogenase (rate limiting enzyme)
- produced C5 sugar ribose required for synthesis of:
- nucleotides
- DNA+RNA
- no ATP synthesised
- CO2 produced
what is NADPH required for
NADPH required for
- reducing power in biosynthesis
- maintenance of GSH levels
- detoxification reactions
• Describe the clinical condition of glucose 6-phosphate dehydrogenase deficiency and explain the biochemical basis of the signs and symptoms.
- decreased G6PDH activity limits amount of NADPH
- NADPH required for reduction of oxidised glutathione (GSSG) back to reduced glutathione (GSH)
- lower GSH means less protection against damage from oxidative stress
- lipid peroxidation
- membrane damage
- lack of deformability: mechanical stress
- protein damage
- aggregates of cross-linked Hb (heinz bodies)
- lipid peroxidation
- lower GSH means less protection against damage from oxidative stress
- NADPH required for reduction of oxidised glutathione (GSSG) back to reduced glutathione (GSH)
what enzymes are involved in digestion of carbohydrates and where?
Saliva: amylase
Pancreas: amylase
Small intestine: lactase, sucrase, pancreatic amylase, isomaltase
Why is cellulose not digested in humans
No enzyme to break down beta 1-4 glycosidic bonds in dietary fibres
Identify 3 clinical features of primary lactase deficiency
- absence of lactase persistence alleles
- only occurs in adults
- allele has highest prevalence in northwest europe
Identify 3 clinical features of secondary lactase deficiency
- injury to small intestine
- both adult + infants
- generally reversible
4 clinical conditions that cause injury to small intestine, leading to primary lactase deficiency
- gastroenteritis
- Coeliac disease
- Crohn’s disease
- Ulcerative colitis
Describe 3 features of congenital lactase deficiency
- extremely rare
- autosomal recessive defect in lactase gene
- cannot digest breast milk
5 symptoms associated with lactase deficiency
- bloating
- flatulence
- diarrhoea
- vomiting
- rumbling stomach
How are monosaccharides absorbed?
- active transport by SGLT1 into intestinal epithelial cells
- active transport by GLUT2 into blood supply
- facilitated diffusion by transport proteins GLUT1-GLUT5 into cells
4 tissues with absolute requirement for glucose
- neutrophils
- eye lens
- RBC
- innermost cells of medulla
Describe the glucose dependency of the brain
CNS prefers glucose but can use ketone bodies for some energy requirements in times of starvation
Identify 3 clinical features of hyperlactaemia
- lactate concentration 2-5mM
- below renal threshold
- no change in blood pH/buffering capacity
Outline fructose metabolism
- dietary sucrose hydrolysed by sucrase -> glucose + fructose
-> absorbed into blood stream - fructose metabolised mostly in liver
- by fructokinase to fructose 1 phosphate
- by aldolase to glyceraldehyde-3-phosphate (intermediate of glycolysis )
Describe clinical features of essential fructosuria
- fructokinase missing
- fructose in urine
- no clinical signs
Describe clinical features of fructose intolerance
- aldolase missing
- fructose 1 phosphate accumulates in liver
-> toxic: liver damage - treatment: remove fructose from diet
