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Medical Biochemistry lecture notes | Block 1
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Samenvatting Marks' Basic Medical Biochemistry - Biochemistry (AB_1137)
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MARKS' BASIC MEDICAL BIOCHEMISTRY: A CLINICAL APPROACH SIXTH, NORTH AMERICAN EDITION BY MICHAEL A. LIEBERMAN PHD (AUTHOR), ALISA PEET MD (AUTHOR)
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Fat, cholesterol & atherosclerosis
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Medical BiochemistryLecture 1 – Overview of human metabolism
Book chapter 1-3
What is a metabolite?
Regulated by:
- Hormones
- Metabolite level
- Lifestyle
Food sources:
- Carbohydrates only thing the brain can use
- Proteins amino acids combined with peptide bonds, important to generate glucose
- Fat (triglycerides) composed of glycerol with three fatty acids attached
All excess fuel is stored as fat
Pathways:
- Glycolysis central pathway
- TCA cycle
Big three (metabolites):
- Glucose-6-phosphate
- Pyruvate
- Acetyl CoA
dG > 0 endothermic, driven by energy generating processes
dG < 0 exothermic, driven by ATP hydrolysis
Metabolic roads to Acetyl CoA:
- Fatty acid, palmitate
- Ketone body, acetoacetate
- Sugar, glucose
- Pyruvate
- Ethanol
Free energy carriers:
- ATP
- GTP
- NAD(P)H
- FADH
Glucose oxidation, storage, synthesis
Amino acids protein synthesis, oxidation, nitrogen compounds
Fats storage, oxidation, synthesis
,Burning food oxidation by O2, energy as ATP, the rest lost as heat
1. ATP synthase + proton gradient ATP
2. ADP ATP: enzyme stops
3. No regeneration of NAD+
Isocitrate dehydrogenase (TCA cycle) NAD+ is needed for process
1500 calories 60 kg ATP
Sufficient ATP: Acetyl CoA fat
Excess glucose fat
Negative nitrogen balance body protein breakdown
More nitrogen excretion during fasting
Ketone bodies:
- Beta-hydroxybutyrate
- Acetoacetate
Can be used by the brain after prolonged starvation to prevent the brain from consuming
essential proteins in the brain itself
, Lecture 2 - Carbohydrates and glucose management
Brain keeps 5 mM glucose in the blood fuel
Glucose is stored in the liver as glycogen in muscles stored ONLY for muscle use
Sugars (stereo-isomers):
- D-glucose
- D-mannose
- D-galactose
Direction of hydroxy groups makes the difference between them
These sugars can make ring structures alpha or beta isomer
3D changes are large enzymes needed for specific sugars
Dietary sources of carbohydrates:
- Starch, plants large glucose polymers, linear or , several enzymes needed for degradation
into monomers (e.g. amylase in saliva, sucrase and lactase intestines for monomers)
- Fibers we cannot digest BUT can be digested by microflora in the gut
- Dairy
- Processed Western food
Uptake:
- Facilitated transport gradient
- Active transport (intestinal epithelium) coupling to pumps
Lactose intolerance (intestines): failure of lactose cleavage into galactose and glucose lactose
build-up microflora will cleave it gas and diarrhea
Galactosemia (liver): failure of galactose conversion into glucose WG
Fructosemia: deficiency of the enzyme aldolase B accumulation of glucose-1-phosphate
glucose-1-phosphate takes up all the phosphate shortage of phosphate no ATP synthesis
Glycogen: consists of many branches of glucose speeds things up; branches can easily be chopped
off
Liver glucose-6-phosphatase can convert glycogen back into glucose?
Muscles
- Glycogen synthase synthesis
- Glycogen phosphorylase mobilization
Muscle: insulin reactive glucose uptake, epinephrin reactive glucose uptake
Liver: insulin reactive glucose breakdown?, glucagon reactive glycogen degradation to
replenish glucose levels
Glucagon ONLY acts in the liver
Glucagon/epinephrine (similar mechanism, except for only epinephrine also acts in the muscle):
1. Activation of PKA
2. Phosphorylation of enzymes
Glycogen phosphorylase activation
Glycogen synthase inactivation
Insulin does the reverse
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