Medical Biochemistry lecture notes | Block 1

Medical Biochemistry
Lecture 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