Biochem 1 Flashcards
Dietary energy: Calories per 1g protein/carb/fat/ethanol?
Protein, Carb: 4cal/1gm
Fat: 9cal/1 gm
Ethanol: 7cal/1gm
Medium chain Acyl-CoA dehydrogenase deficiency (MCAD)
[Findings]
> Acyl-CoA DHG: catalyzes first step for B-oxidation of Fatty Acid
Findings: Hypoglycemia, Hypoketotic hypoglycemia (no ketones in urine during hypoglycemia or fasting periods)
G6PD deficiency.
What pathway is G6PD in? Findings, associations?
G6PD is the rate-limiting enzyme in HMP shunt (main source of NADPH, a reducing molecule).
>Findings: Acute hemolytic anemia, Heinz bodies (Bite cells), immunodeficiency.
>Assctd w/: infections (pneumonia, viral hepatitis), fava beans, drugs (primaquine, sulfa drugs) – RBCs unable to maintain sufficient reduced glutathione in times of oxidative stress
Fructokinase deficiency (essential fructosuria). What happens? Findings?
> Fructokinase: fructose –> fructose-1P (liver) – eventually enters glycolysis.
Hexokinase takes over in fructokinase def.: fructose –> Fructose-6P – glycolysis.
*Generally asx; Fructose excreted unchanged in urine
Galactokinase deficiency.
What happens? Findings?
Galactokinase: galactose –> galactose-1P
Excess galactose (galatosemia) –> galactitol (aldose reductase), galactate (galactose oxidase).
>Galactate – HMP shunt
>Galactitol – accumulates in cells – cataracts (failure to tract object or develop social smile).
High anion gap metabolic acidosis
Equation
(MUDPILES)
Anion gap = Na - (Cl + HCO3)
*Methanol, Uremia, Diabetic ketoacidosis, Propylene glycol / Paraldehyde, Isoniazid / Iron, Lactic acidosis, Ethylene glycol (antifreeze), Salicylates (aspirin)
Vit B12 Deficiency.
B12 cofactor for what enzymes?
> Methylmalonyl-CoA mutase (methylmalonyl-coa –> succinyl-CoA).
Methionine synthase (homocysteine –> methionine).
Labs: inc. methylmalonate, inc. homocysteine
Vit B12 Deficiency
[Findings]
Megaloblastic anemia w/ neuro deficits.
>Inc. homocysteine; Inc. methylmalonate – disrupts myelin synthesis (Subacute combined degeneration).
>Affects dorsal columns (no proprioception or vibration, Romberg sign), Lateral corticospinal tracts (spastic weakness, hyperreflexia).
Hepatic encephalopathy
[MOA]
Cirrhotic liver can’t metabolize nitrogenous wastes.
Ammonemia – NH3 crosses BBB – inc. glutamine prodn in astrocytes – inc. intracellular osmolarity – swelling – inhibits glutamine release – no glutamate production – no excitatory neurotransmission.
Hormone-sensitive lipase.
Action, Role in starvation state?
HSL is triggered by stress hormones to induce lipolysis.
Triglycerides broken down – Glycerol (gluconeogenesis), FFA (ketone bodies, TCA).
*Most tissues use ketones and FFA during starvation (except brain, RBCs)
Peroxisomal diseases
Zellweger syndrome, Refsum dse
Very long chain FA and branched FA can’t undergo mitochondrial B-oxidation – metabolized in Peroxisomes instead.
*VLCFA – special B-oxidation.
*Branched FA – alpha-oxidation.
>Zellweger syndrome: infants can’t form myelin in CNS; hypotonia, seizure, hepatomegaly, mental retardation
>Refsum dse: defect in alpha-oxidation, inc. phytanic acid (branched FA); neuro disturbances; avoid chlorophyll diet
Pyruvate kinase deficiency
[MOA, Findings]
Pyruvate kinase: PEP –> Pyruvate – ATP
RBCs need ATP to maintain membrane structure.
Damaged RBCs removed by splenic red pulp – hemolytic anemia, splenomegaly (hyperplasia).
Primary Carnitine deficiency
[MOA, findings]
Defect in protein that transports carnitine across plasma membrane – needed so FA can be shuttled into mitochondria to be used in B-oxidation and Krebs.
No ATP (cardiac, skeletal muscle).
No ketone bodies (acetoacetate) made during hypoglycemic state.
>Findings: Myopathy, cardiomyopathy, hypoketotic hypoglycemia, inc. muscle TGLs
Antioxidants (3)
Superoxide dismutase
Glutathione peroxidase
Catalase
Phosphorylase kinase activates glycogen phosphorylase, w/c breaks down glycogen.
What is the role of phosphorylase kinase in Liver vs. skeletal muscle?
> Liver: glycogen used to maintain blood glucose; phosphorylase kinase activated by Epi and glucagon (via Gs to inc. cAMP).
Skeletal muscle: glycogen used for muscle contraction, but Epi has a lesser role vs ACh, w/c inc. intracellular Ca to synchronize muscle contraction w/ glycogen breakdown (Ca activates PK) – energy for anaerobic muscle contraction.
