Carbohydrate metabolism Flashcards
1
Q
Blood glucose level
A
~5mM
2
Q
Tissues that have absolute glucose requirement (4 things)
A
- Erythrocytes (no mitochondria)
- Neutrophils (low O2)
- Innermost cells of renal medulla (low O2)
- Lens of eye (no mitochondria)
3
Q
What is starch broken down into by salivary amylase?
A
Oligosaccharides
4
Q
Disaccharidases attached to brush border membrane of small intestine (5 things)
A
- Lactase
- Pancreatic amylase
- Isomaltase
- Glycoamylase
- Sucrase
5
Q
Why isn’t cellulose digested?
A
Beta 1,4 linkages can’t be digested as bacteria producing those enzymes not present in human GI tract
6
Q
Primary lactase deficiency (3 things)
A
- Lack of lactase persistence allele
- Highest prevalence in northwest europe
- Only occurs in adults
7
Q
Secondary lactase deficiency (3 things)
A
- Caused by injury to small intestine: gastroenteritis, coeliac, Crohn’s, ulcerative colitis
- In both adults and infants
- Generally reversible
8
Q
Congenital lactase deficiency (3 things)
A
- Autosomal recessive defect in lactase gene
- Very rare
- Can’t digest breast milk
9
Q
Absorption of monosaccharides (4 things)
A
- SGLT1: active transport into intestinal epithelial cells
- GLUT2: passive transport into blood supply
- GLUT1-GLUT5: facilitated diffusion into target cells
- GLUTS have different tissue distribution and affinities
10
Q
GLUT1 (3 things)
A
- Foetal tissues
- Adult RBC
- Blood-brain barrier
11
Q
GLUT2 (4 things)
A
- Kidney
- Liver
- Pancreatic beta cells
- Small intestine
12
Q
GLUT3 (2 things)
A
- Neurones
- Placenta
13
Q
GLUT4 (2 things)
A
- Adipose tissue
- Striated muscle
14
Q
GLUT5 (2 things)
A
- Spermatozoa
- Intestine
15
Q
Why are there so many steps in glycolysis (4 things)?
A
- Chemistry easier in small stages
- Efficient energy conversion
- Gives versatility
- Can be controlled
16
Q
Phase 1 of glycolysis (3 things)
A
- Phosphorylation makes glucose -ve so can’t go back across plasma membrane
- Irreversible step due to large -ve free energy change
- Commiting step of metabolism of glucose via glycolysis
17
Q
Glycerol phosphate- important intermediate (5 things)
A
- Important to triglyceride and phospholipid biosynthesis
- Produced in adipose and liver tissue
- Lipid synthesis in adipose tissue requires glycolysis
- Liver can also phosphorylate glycerol directly
- Enzyme: glycerol 3 phosphate dehydrogenase
18
Q
1,3- bisphosphoglycerate- important intermediate (3 things)
A
- Produced in RBC
- Regulator of Hb-O2 affinity (promotes release)
- Enzyme: bisphosphoglycerate mutase
19
Q
Glycolysis- clinical application (3 things)
A
- Rate of glycolysis up to 200x greater in cancer
- Measure uptake of FDG (radioactive modified hexokinase substrate)
- Imaging with positron emission tomography (PET)
20
Q
Allosteric regulation of phosphofructokinase in muscle (4 things)
A
- Inhibited by high ATP (ratio of AMP:ATP)
- Inhibited by high citrate
- Stimulated by high AMP
- Stimulated by F-1,6-BP
21
Q
Hormonal regulation of phosphofructokinase in liver (3 things)
A
- Inhibited by glucagon
- Stimulated by insulin
- Done by covalent modification (phosphorylation)
22
Q
Hexokinase regulation
A
Product inhibition by G-6-P
23
Q
Pyruvate kinase regulation (2 things)
A
- Hormonal activation
- Stimulated by high insulin:glucagon ratio
24
Q
Why do some cells convert pyruvate to lactate (2 things)?
A
- Some cells have no stage 3 or 4 of metabolism (e.g. RBC, lens of eye)
- Supply of O2 is sometimes inefficient
25
Lactate production without major exercise- which tissues? (5 things)
- RBC
- Skin
- Skeletal muscle
- Brain
- GI tract
26
Lactate production under strenuous exercise (2 things)
- Plasma levels increase 10 fold in 2-5 mins
- Back to normal by 90 mins
27
Lactate production under pathological situations- 2 examples
- SHOCK
- Congestive heart disease
28
Lactate dehydrogenase in tissue- which tissues and what happens (2 things)
- RBC, skeletal muscle, skin, brain, GI tract
- In low O2, pyruvate converted to lactate
29
Lactate dehydrogenase in liver and kidney (4 things)
- Impaired in liver disease
- Sensitive to thiamine deficiency
- Alcohol reduces NAD+ available
- Enzyme deficiencies can result in LDH to be deficient
30
What are relative rates of plasma lactate concentration determined by (3 things)?
- Production
- Utilisation (liver, heart, muscle)
- Disposal (kidney)
31
Hyperlactaemia (3 things)
- 2-5 mM
- Below renal threshold
- No change in blood pH (buffering system)
32
Lactic acidosis (3 things)
- Above 5 mM
- Above renal threshold
- Blood pH lowered
33
Where is fructose metabolised?
Liver
34
Essential fructosuria (2 things)
- Fructokinase missing
- Fructose in urine, no clinical signs
35
Fructose intolerance (4 things)
- Aldolase missing
- Fructose-1-P accumulates in liver
- Leads to liver damage and possible death
- Managed by removing fructose and sucrose from the diet
36
Deficiency in which 3 enzymes could cause galactosaemia?
- Galactokinase
- Uridyl transferase
- UDP-galactose epimerase
37
What is galactose used to synthesise (2 things)?
- Glycoproteins
- Glycolipids
38
Where is galactose mainly metabolised?
Liver
39
2 types of galactosaemia
- Galactokinase deficiency (rare)- galactose accumulates
- Transferase deficiency (common)- galactose & galactose-1-P accumulate
40
Problems from galactosaemia and treatment (4 things)
- Galactose enters other pathways: aldose reductase converts it to galactitol
- Depletes lens of NADPH, structure damaged, cataracts
- Accumulation of galactose-1-P affects liver, kidney, brain
- Treatment: no lactose in diet
41
What is C5-sugar ribose used to synthesise in pentose phosphate pathway (2 things)?
- Nucleotides
- DNA & RNA
42
What is NADPH used to synthesise in pentose phosphate pathway (3 things)?
- Fatty acids
- Steroids
- GSH regeneration
43
What is the rate limiting enzyme for pentose phosphate pathway?
Glucose-6-phosphate dehydrogenase
44
GP6DH deficiency (5 things)
- NADPH conc. decreases in RBC
- Needed to reduce oxidised glutathione
- Disulphide bonds formed due to oxidative stress
- Aggregated proteins leading to Heinz body formation
- Haemolysis (anaemia)
45
Pyruvate dehydrogenase- what is it and key points (4 things)
- Large multi-enzyme complex (link reaction)
- Requires coenzymes FAD, Thiamine pyrophosphate & lipoic acid
- Sensitive to vitamin B1 deficiency
- Reaction it carries out is irreversible
46
What activates pyruvate dehydrogenase (5 things)?
- Pyruvate
- CoA
- NAD+
- ADP
- Insulin
47
What inhibits pyruvate dehydrogenase (4 things)?
- Acetyl CoA
- NADH
- ATP
- Citrate
48
Products of TCA cycle from one molecule of glucose (4 things)
- 2x FADH2
- 4x CO2
- 6x NADH
- 2x ATP/GTP
49
Regulation of TCA cycle (3 things)
- Isocitrate dehydrogenase
- alpha-ketoglutarate dehydrogenase
- ATP:ADP/NADH:NAD+ ratios
50
Intermediates of TCA cycle key points (3 things)
- Fatty acids, AA & haem in liver
- Neurotransmitters in brain
- Replacements for intermediates can come from breakdown of AA
51
How is ATP synthesised during oxidative phosphorylation (3 things)?
- Electrochemical gradient
- Protons return across membrane via the ATP synthase
- Also known as proton translocating ATPase/complex
52
How much ATP is produced in oxidative phosphorylation (2 things)?
- 5 moles for every 2 NADH
- 3 moles for every 2 FADH2
53
How is energy produced in oxidative phosphorylation?
Energy from the dissipation of the p.m.f is coupled to the synthesis of ATP from ADP
54
How is oxidative phosphorylation regulated?
Ratio of ATP:ADP
55
Inhibition of oxidative phosphorylation and example (2 things)
- Inhibitors block electron transport
- e.g. cyanide
56
Uncoupling of oxidative phosphorylation (3 things)
- Uncouplers make cristae more permeable to protons
- No drive for ATP synthesis as p.m.f is dissipated
- Instead energy used to generate heat
57
Ox/Phos diseases (3 things)
- Genetic defects in proteins encoded by mtDNA
- Some subunits of PTCs and ATP synthase
- Decrease in electron transport and ATP synthesis
58
Brown adipose tissue in uncoupling (5 things)
- Has thermogenin (UCP1): naturally occurring coupling protein
- Noradrenaline activates lipase
- Fatty acid oxidation
- Fatty acids activate UCP1
- UCP1 transports H+ back into mitochondria
59
Oxidative phosphorylation key points (4 things)
- Needs membrane complexes
- Needs O2
- Energy coupling is indirect through p.m.f
- Major process for ATP synthesis in cells needing large amounts of energy
60
Substrate level phosphorylation (4 things)
- Needs soluble enzymes
- Limited extent in absence of O2
- Energy coupling direct through hydrolysis of bonds
- Minor process for ATP synthesis in cells needing large amounts of energy
61
Which enzyme catalyses reaction to phosphorylate glycerol?
Glycerol kinase
