Biochem Flashcards
Pyruvate kinase deficiency?
GLYCOLYSIS
Benign
↓pyruvate -> ↓ATP in RBCs -> ↑ hemolysis -> ↓ O2 delivery
Compensation:
1) ↑ ATP synthesis in liver
2) ↑ 2,3-BPG -> ↓ O2-Hb binding
↑ O2
Aldolase B deficiency? (fructose intolerance)
GLYCOLYSIS
Accumulation of Fructose-1-P → TOXIC → poor feeding / failure to thrive in infants
- Depletion of Pi req. for glycolysis
- Fructosuria
Galactose-1-P uridyltransferase deficiency ? (Galactosemia)
GLYCOLYSIS
Accumulation of Galactose-1-P → TOXIC → brain/kidney damage + liver dysfunction - Jaundice
- Galactosuria
- Aldose reductase reduces accumulated galactose to galactitol → Osmotic damage to lens → CATARACTS
Pyruvate Dehydrogenase (PDH) deficiency? (rare)
TCA
Pyruvate accumulation
↑ Lactate -> Lactic acidosis
↓Acetyl-coA -> ↓ TCA cycle -> ↓ ATP -> neurodegeneration
Thiamine (Vit B1) deficiency [Beri-Beri] ?
TCA
- Thiamine req. to prod. TPP (essential cofactor for PDH and α-KG DH + Transketolase)
Chronic deficiency → ↓ATP
1) neurological: neuropathy, encephalopathy, cognitive impairment
2) cardiac : congestive cardiac failure
Arsenic/mercury poisoning?
TCA
- Arsenic / mercury inhibits lipoic acid (essential cofactor for PDH & α-KG DH)
Acute poisoning → ↓ATP → neurological dysfunction → organ failure → coma/death
Chronic poisoning → Skin (dew drops on a dusty road) + Nails (Mees lines)
Arsenic poisoning → recognizable by garlicky odor
MELAS
OXPHOS
- Myopathy, Encephalomyopathy, Lactic Acidosis & Stroke-like episodes
- Mutation in mitochondrial tRNA → decreased ETC complexes (except II) → decreased ATP → neurological / muscle dysfunction
- decreased ETC activity → decreased TCA cycle activity → Accumulation of pyruvate & lactate → Lactic acidosis
Characteristics of OXPHOS mitochondrial disease?
- mitochondrial DNA is MATERNALLY inherited
- only carrier females can pass it down
- in every generation, affect both sexes
- it encodes for all ETC complex subunits EXCEPT COMPLEX II & for ribosomes / tRNA for synthesis
Mitochondrial poisons?
OXPHOS
I : Rotenone (rat poison)
II : Malonate
III : Antimycin A (fish poison)
IV : Cyanide / CO
ATP synthase : Azide
Dinitrophenol (herbicide / illegal weight loss drug) : Increase proton leak across membrane -> Increase heat generation
G6PD deficiency?
HMP SHUNT
* X-linked recessive disease
Decreased production of NADPH in RBCs
[needed to maintain glutathione in reduced form] → less protection against oxidative stress in RBCs
1. Less severe form:
inadequate NADPH to protect against oxidative stress caused by drugs (anti- malarial, sulfur-based antibiotics), infections, mothballs → oxidation of proteins in RBCs (Heinz bodies) → decrease in membrane plasticity → increases hemolysis → Jaundice + Sclera icterus
2. Severe form:
infants with increased hemolysis → anemia + increase in bilirubin → cross BBB → neurological damage = Kernicterus **
- BUT G6PD Deficiency may confer resistance to malaria by decreasing production of NADPH (utilised by the malaria parasite in RBCs)
Glucose-6-phosphatase deficiency?
GLUCONEOGENESIS
1. Can’t untrap glucose → Accumulation of G6P → Hypoglycemia
- Accumulated G6P
- HMP shunt → increased nucleotide metabolism → Increased uric acid
- Glycogen synthesis → Increased glycogen → Organomegaly
- Accumulation of pyruvate → Increased lactate
Pyruvate carboxylase deficiency?
GLUCONEOGENESIS
- Very rare, short life span of 6 months
- Metabolic block in Pyruvate → OAA (1st step of 1st hurdle)
- Accumulation of Pyruvate → increased Lactate
- Depletion of OAA -> less TCA activity
- decreased ATP production
- decreased gluconeogenesis → hypoglycemia
Glycogen storage diseases?
Viagra Pills Cause A Major Hardon
I : Von Gierke -> G6Pase
II : Pompe -> 1,4-glucosidase
III : Cori -> Debrancher enzyme
IV : Andersen -> Branching enzyme
V : McArdel -> Muscle glycogen phosphorylase
VI : Her’s -> Liver glycogen phosphorylase
Which glycogen storage disease cause block in synthesis?
Type IV Andersen
- deficiency of branching enzyme
- accumulation of abnormal glycogen
- Hepatomegaly
- Early death
Symptoms of Von Gierke?
G6Pase deficiency
fasting hypoglycemia, organomegaly, lactic acidosis, increased uric acid (possibly gout)
Symptoms of Cori?
Type III
Debrancher enzyme deficiency [4:4 transferase + 1,6-glucosidase]
Fasting hypoglycemia
Symptoms of McArdle?
Type V
Deficiency in muscle glycogen phosphorylase
Exercise-induced muscle pain, cramps
How are carbohydrates absorbed?
Glucose & Galactose -> SGLT1 (secondary active transport) -> GLUT2 (facilitated transport)
-> SGLT1 is driven by Na-K-ATPase pump
Fructose -> GLUT5 -> GLUT2 [facilitated diffusion]
Importance of PFK1?
Catalyses the :
Irreversible step
Entry point to glycolysis
Major point of regulation
Importance of pyruvate kinase?
GLYCOLYSIS
Catalyses the :
Irreversible step
Substrate-level phosphorylation
Point of regulation
How’s PFK-1 and pyruvate kinase regulated by energy state?
PFK1 : inhibited by ATP & citrate, activated by AMP
PK : inhibited by ATP
Location of all carb metab pathways?
Glycolysis : cytoplasm
TCA : mitochondrial matrix (except SDH in inner membrane)
OXPHOS : mitochondria inner membrane
HMP shunt : cytosol
Gluconeogenesis : Cytosol
How does fructose & galactose enter glycolysis?
Fructose ->(fructokinase) -> F1P -> (Aldolase B) -> DHAP <-> G3P
Galactose -> (Galactokinase) -> Galactose-1-P -> (Galactose-1-P uridyltransferase) -> G1P -> G6P
How to regenerate NAD+ from NADH?
- Aerobic : OXPHOS shuttle
- Anaerobic : Cori cycle, when Pyruvate -> Lactate
