Jan29 M2-Normal and Abnormal Carbohydrate Metabolism - 1 Flashcards
3 classes of macronutrients
lipids, polysaccharides, proteins
(EXAM) 3 stages of catabolism for macronutrients
1: Hydrolysis into monomers
2. conversion to acetyl coa
3. oxidative phosphorylation of acetyl coa
what ar the building blocks of lipids
glycerol and fatty acids
what is energy in the body exactly, what do we get out of glucose
ATP (high energy phosphate bonds)
main source of polysaccharides in our food. which polysaccharide + all its breakdown disaccharide and monosaccharides
potatoes, rice, pasta: starch. maltose. glucose + glucose.
what breaks down maltose into glucose + glucose
a disaccharase in the intestinal epithelium
lactose kind of molecule, food source and components
disaccharide. milk. glucose + galactose
sucrose kind of molecule, food source and components
disaccharide. plant products and sugar cane. glucose + fructose
basis for lactose intolerance + type of disease
deficiency in lactase (disaccharase). not genetic. function of bowel lost over time (mostly in early childhood). NOT genetic
symptoms in lactose intolerance + reason
flatulence and diarrhea. lactase not digested so goes to bowel and bacteria transform it to gases
sucrase deficiency charact.
rare, Inuit population, same things occur as lactase deficiency
where glucose is the most metabolized
liver
which monosaccharides can be transformed to glycogen (repolymerized) for storage
glucose and galactose
GLUTs: how many and why they differ
- expressed in specific cell types bc have specific properties
(EXAM) two GLUTs of interest + tissues
glut2: liver and pancreas
glut 4: muscle and adipose tissue
(EXAM) glut2 features and why useful to the liver
bidirectional transport bc livers metabolize glucose but also exports it when we’re fasting
(EXAM) glut2: why useful to the pancreas
allows beta cell to sense circulating glucose levels
(EXAM) 3 main insulin target tissues
liver, fat, muscle
(EXAM) glut4 in what tissue + very important property that is unique to it
fat and muscle.
Sensitive to insulin**
(EXAM) how insulin acts on glut4
vesicles carrying glut4 but just sitting in the cell fuse with the plasma membrane
2 drivers of diabetes worldwide nowadays
obesity (more calories intake)
sedentarity (less calories burned)
type 1 DM pathophgy and % of DMs
autoimmune destruction of insulin producing beta cells. 10%
type 2 DM pathophgy and % of DMs
insulin made but not as much glut4 is put in the membrane. 90%
type 2 DM: what tissue is most affected
skeletal muscle
type 2 DM first stage (Early)
pancreas ramps up insulin prod and glucose levels stay normal
type 2 DM 2nd stage (later)
beta cells lose ability to produce high amount of insulin (huge amount damages the cell)
other disorders of macronutrients metabolism and diseases that come with these disorders
fat metab and protein metab deregulated.
stroke, kidney failure, cognitive dysfct, muscle weakness, dementia, sarcopenia, bone more prone to fracture
(EXAM) first enzyme of glycolysis: 2 enzymes possible
hexokinase and glucokinase
(EXAM) hexokinase charact and what cells
cells other than liver and pancreas. enough activity to make enough glucose for cell to survive
(EXAM) glucokinase charact and what cells
liver and pancreas. extra activity to break down glucose.
glucokinase advantages over hexokinase
more dynamic range of activity, more sensitive to glucose levels (works harder at higher glucose) and much higher max velocit
why glucokinase does extra activity
also responsible for making fat in the body so breaks down glucose into metabolites then used to synthesize fats which are secreted and circulate
(EXAM) why is the first step of glycolysis (glucose to glucose 6 P) irreversible
requires ATP consumption. REGULATED STEP
2nd step (glucose 6 P to fructose 6 P) what kind of rx
isomerization
(EXAM) 2nd step limiting enzyme in glycolysis and its job
PFK1. fructose 6 P to fructose 1-6 bisP
what controls PFK1 activity
hormones and metabolites in the cell
what happens in glycolysis after get fructose 1,6 bisP and why is it important
aldolase splits it into 2 metabolites. important bc results of downstream rxs must be multiplied by 2
what does aldolase yield from fructose 1,6 bisP
DHAP and glyceraldehyde 3P
link between DHAP and glyceraldehyde 3P + which is used for rest of glycolysis
can be converted into each other by triose phosphate isomerase. DHAP made into glyceraldehyde 3P (used for the rest of glycolysis)
(EXAM) why glyceraldehyde 3P to product step is important
NADH (+ H+) is made from NAD+ + Pi.
(EXAM)glyceraldehyde-3P + product. product name and enzyme in this rx
GAPDH. make 1,3-biphosphoglycerate
(EXAM) 1,3-biphosphoglycerate + product step: why important
makes ATP (gives one P to ADP)
(EXAM) 2nd step in glycolysis where ATP is yielded and product of this step
phsophoenoylpyruvate to pyruvate (done by pyruvate kinase).
ADP to ATP
(EXAM) 3 irreversible and regulated steps of glycolysis and why
1st step (GK or HK) and PFK1 step. (because consume ATP) + pyruvate kinase step (to make pyruvate)
(EXAM) glycolysis: investments, products and end result in terms of ATP, NADH and pyruvate
invest: 1 glucose + 2 ATP (step 1 and 3)
product: 4 ATP + 2 NADH + 2 pyruvate
NET: 2 ATP, 2 NADH, 2 pyruvate
(EXAM) insulin: fcts on muscle, fat and liver other than gluT insertion
stimulates transcription of 3 glycolysis genes: GK or HK + PFK1 + pyruvate kinase also called PK (last step)
GK use in pancreas vs liver
liver: provide substrate for fat synthesis
pancreas: tell beta cell how much insulin to release
type 2 diabetes (poor response to insulin): what enzyme is affected + treatment possible
glucokinase (step 1 glycolysis. liver and pancreas).
treatment: small molecule activators of GK
(EXAM) one mutation in GK: disease name and treatment
MODY (maturity onset disease of the young). DON’T need insulin
MODY often confused with what disease and diff between the two
often confused with type 1 diabetes. type 1 DM needs insulin.
MODY doesn’t need insulin
(EXAM) 2 mutations in GK consequence and treatment
permanent neonatal DM (PNDM). Need insulin.
enzyme breaking down sucrose + products
sucrase. gives glucose + fructose
(EXAM) fructose: 2 steps diff in glycolysis and consequence
- fructose kinase makes it fructose 1P
- aldolase B makes it glyceraldhehyde and DHAP
BYPASSES GK regulation/HK regulation
what can happen to glyceraldehyde from 2nd step of fructose glycolysis
- converted to glycerol (backbone for fat synthesis(
2. phosphorylated into glyceraldehyde-3P to use it in glycolysis
important theory on one of the many drivers of obesity
high consumption of fructose (ex. soft drinks) = metab rapidly by liver to make glycerol + acetylcoa to make fat
(EXAM) fructose intolerance cause
genetic mutation in aldolase B
(EXAM) 2 important implications of fructose intolerance
- fructose 1 P is an inhibitor of PFK1
- ATP of the cell is harvested to make fructose 1 P that won’t lead to ATP prod. (phosphate and energy deficiency, liver cells damaged)
symptoms in fructose intolerance
toxicity, tissue damage (liver, kidney), hypoglycemia
(EXAM) why hypoglycemia in fructose intolerance
fructose 1 P inhibits breakdown of glycogen storage. consequence: metabolites like phosphoenoylpyruvate can’t make glucose bc the more upstream pathway is blocked
(EXAM) glycolysis: how it is changed in cancer + name of that
hyperactivated. Warburg effect
* *cancer cell uses glucose faster and makes lactate instead of acetyl-CoA
(EXAM) glycolysis enzymes affected in cancer
HK overexpressed
HK and PK VARIANT is expressed (very active)
basis for PET scan
measure hyperactivity of glycolysis by radiolabelling glucose (add radioactive 18F on a hydroxyl group)
what happens to 18F glucose in the body
phosphorylated but not further metabolized and gets stocked in the cell: seen on imaging
PET used for what
stage cancers and check for metastases
what bacteria can do with pyruvate
ethanol
(EXAM) what our body can do with pyruvate
- make acetyl coa to go in TCA (pyruvate dehydrogenase)
- reduce it to lactate (lactate dehydrogenase)
- make it oxaloacetate (pyruvate carboxylase) (OAA is TCA intermediate)
why transformation of pyruvate into lactate by lactate dehydrogenase is something important
needs a NADH so yields NAD. NADH is a redox metabolite exchanging protons and we need a balance of NAD and NADH in the cell bc used in a lot of places. This rx consumes the NADH produced from glycolysis
what determines if pyruvate made into acetyl coa or lactate
O2 amount in the cell. high O2: make acetyl coa
low O2: make lactate
when do we have low O2 and pyruvate made into lactate
cardioresp exercise/high intensity sport like hockey
why pyruvate to acetyl coa pathway works less in low O2
too much pyruvate to the few O2 left (O2 consumed too fast)
lactate effect on muscle + how it is metabolized
muscle pain.
lactate goes in blood, reaches lier, metab by reverse rx (lactate to pyruvate)
clinical use of lactate
measure in ill patients to check if severe illness bc shows something is wrong
high lactate can be marker of what
O2 deficiency, MI, bleeding (not delivering O2), hypotensive states.
